KochLab
We are a bunch of people at the University of New Mexico that specialize in kicking ass in science. We focus on two aspects of biophysics: kinesin molecular motors and DNA unzipping.
Posts
It has been a very long time since I updated our research blog. I have left out many, many important updates, including all of Larry's results, that led to his recent graduation as our lab's first to receive a Ph.D.! He also got a job that he even likes, so I am quite remiss in my updates. I do apologize, and I would promise that I will keep up to date more, but I know none of you would believe that.
I actually am much better at keeping updates going out on FriendFeed. I don't know how long FriendFeed will be around, but for now it is still working OK and is an easier platform for posting information and discussing. So, I am going to embed a FriendFeed post below that describes Andy Maloney's latest results with the microtubule gliding assay for kinesin-1. He has worked very hard for two years, and along with Larry Herskowitz has produced a robust and efficient system for studying microtubule gliding speeds in the gliding assay. I am really proud of both of them for the system they've produced!
Below will be the FriendFeed update, and here are some relevant links:
- First chapter of Andy Maloney's open dissertation.
- Readme file for our gliding assay open data (all of our data is public domain).
- Our channel on youtube, which shows a lot of the gliding assay videos.
- Andy's Instructubles page for how to build the objective heater for temperature stabilization.
- Andy's preprint on surface passivation effects in the gliding assay (submitted to PLoS ONE, revision to be submitted this week).
- Larry's preprint on a kinetic model for kinesin-1 (submitted to PLoS ONE, revision to be submitted within a month).
In one of my most recent (and frequent) brainstorms, I came up with a really great idea. Koch and I were hiking on the La Luz Trail:
View La Luz Trail to North Tramway Trail in a larger map
At some point on the trail, we came really close to some really nice houses. That's when it hit me...
...We should go door-to-door discussing our research requesting donations to help our lab. At first I was kidding, and perhaps I still am, but just think about it. Having a private investor could be a lot of fun. You have a more personal interaction level with your funding source. First you are actively discussing a topic you are passionate about with a potential investor. Sure you can do that when writing grants, but there is structure and order to that which may be unnecessary. In this manner, you can get back to basics and prove your love of your research.
I also discussed how we could host a bunch of lab visits to let the investor check in. Let them see what there money is going to. There can be tons of other organized meetings. Various lunches and dinners would allow for an even more personal interaction and may even spark a new friendship. Of course your funding source would be invited to talks you give, which would allow them to learn about any advances you make, while also seeing the big picture.
The best aspect of this is that a rich person probably has more rich friends and if your philanthropist likes your research enough, he will tell his friends and maybe they would like to donate as well. Maybe he/she will host an event to support your cause and try to get all his friends to donate. All in the name of science.
Just think about what the wonders of having a financial backer could bring. The possibilities are endless. And if you are worried about getting rejected while going door-to-door then say to yourself, "It's no different than when I submit a proposal!"
I haven't updated people in a very long while as to what I have been doing in the KochLab. Technically I haven't been doing anything in there at all. From January to June I have been working with a collaborator in their lab... the Osley Lab. Koch sent me over there to learn basic level molecular biology and to begin the process of shotgun cloning.
You can follow all of my notes at OpenWetWare, but I will sum it up for you here. To make a long story short, I digested the ENTIRE yeast genome (Saccharomyces cerevisiae) with both XhoI and EcoRI. I then ligated the resulting fragments to an unzipping construct designed by Koch. Now we are ready to unzip. Of course there is still a little bit to work out, and even more to follow up on, but theoretically I have unzippable DNA fragments. We won't find out till we try.
I have shared a presentation I made for the first ever KochLab Symposium (posted on SlideShare), basically because I am too lazy to upload any of the pictures I have made and this talk contains everything.
As I mentioned you start with genomic yeast DNA. I digested the DNA with the restriction enzymes mentioned. I also digested pBluescript with the same RE's. I ligated the resulting fragments into the plasmid. From here I was able to make clones of whatever fragments managed to find their way into the plasmid, using E. coli. Using the color selection of pBluescript, I selected about 20 clones which would be used for sequencing and unzipping preparation.
After extra the cloned plasmid DNA I digested each sample with SapI and NotI. From there I picked about 5 samples that looked different from each other. Even though there is a low chance that the same sequence of DNA would be 2 separate clones, it was best not to take the chance. After selection and digestion, we sent a small portion of the samples off for sequencing.
The remaining sample was ligated to an unzipping construct. The SapI digested fragments were ligated to a specially designed oligo with a SapI overhang. The NotI fragments, likewise, were ligated to an oligo with a NotI overhang. There were other differences, but they don't need to be discussed here. The oligos are special because they contain a digitylated site, a nick, and a biotinylated site respectively. This means that I can attach the DNA to glass using anti-dig, attach a microsphere (streptavidin coated) to the biotin, and unzip utilizing the nick between the two. Sweet isn't it?
Once the tweezers are completed and calibrated we will test my work to make sure everything is peachy. We are almost there and I'll update at the end of the summer to report our progress until that point. Hopefully by then I should officially be a Ph.D. candidate!
I have been into graphic design for 2 years now and I am getting quite good (if I do say so myself). I started because nobody in the lab (out of Koch, Larry, and I) had any experience and I had wanted to get into web design type stuff. Then Koch and I determined that any future successful lab needs a brand. What was once the Koch Lab became KochLab (very different, I know) and I commenced work on an official logo.
I knew I wanted the theme to be cooking. Why? Mostly because nobody could say Koch's (pronounced cook) last name properly. Also because cooking is awesome. I then started work on the frying pan logo that has swept various presentations and OWW by storm. Next I got to work on a thumbnail version of the logo, which evolved into a chef hat. To add some final punch we incorporated merchandise this past Christmas.
Now we are beginning a new project and I thought I would make a new logo for this project. Previously Andy and I collaborated on a fun logo that got named Kiney. That was fun to make, but I wanted a vector graphics image and this is what I came up with:
If you want to see all the KochLab logos and their progression check this out.
What's been koching?
I have been getting asked the question a lot recently, in various forms and in various levels of directness: "how come you've had your new lab for two and a half years and you still don't have optical tweezers data?" This question comes about because of my mid-probationary tenure review, grant applications, collaborations, and just general behind-the-back chitter chatter. I have to stress that I find this question perfectly reasonable and totally valid. Most new professors get their lab up and running much more quickly than I have. Even I expected to be "up and running" sooner--but I am not disappointed. Rather, I am quite happy with where we are at, because my plan was to have the students involved in every aspect of our lab start-up, and to fundamentally understand optical tweezers, why we're building them, and what our impact is going to be. I've spent (or reserved) the majority of my start-up funds ($200K) on students. Those students are now poised to have a really great optical tweezers and a deep understanding of how we are going to make biological discoveries with this tool.
During my first two plus years as an assistant professor, I have failed at expressing my lab mentorship vision to my colleagues at UNM. I do think I've succeeded in privately communicating my vision to my department chair, mostly via my written annual updates and goals. But I've not communicated my plan to the vast majority of people who care about me, or at least care about me bringing in money. One of my graduate students, Andy, helped me realize yesterday this problem and I'm really happy that I now see it. Further discussion of this non-talent, I think I'll save for my other blog. My main point here is to just acknowledge that it's been my own failure to engage and communicate that has created this minor issue (only a major issue if I don't get my contract renewed, which is unlikely I think). My goal will be to much more aggressively communicate my vision to people when this issue comes up in face-to-face conversations. Maybe something like this:
"I know! I'm itching for the data to start coming out too. We've been much slower than average because my philosophy is that one of the missions of my lab is to mentor students. The students need to learn and need to be involved in the management of the construction of our instrumentation, the designing of our experiments, and even our grant writing. Because of that, we're not as far along in terms of data and publications as many people would have expected. On the other hand we are only a few weeks away from having a kick-ass optical tweezers system that the students have designed and constructed. And these students have a very solid understanding of what we're trying to achieve, and a self-driven motivation to achieve from this point onward. So, many good things are going to happen for us this year, and our rate of achievement over the next few years is going to be much, much higher than it would have been if I had simply built optical tweezers and commanded students to acquire data. Furthermore, because of their intense participation in our lab start-up, these students are going to be very strong in the next stages of their careers--particularly if they have to start-up their own lab."I need to rehearse that. Sort of like my "30 seconds in the elevator with the CEO" kind of speech. Furthermore, when I'm asked this question by certain people, such as those that support all the extra BS and hoops that our graduate students have to jump through, I plan on going further to explain how those hoops and BS substantially impacted the progress of our research. What I have in mind here are the IGERT programs we have with ridiculous non-research requirements (including 4 extra courses) and our physics department's fixation on testing and retesting and retraining our graduate students on undergraduate quantum, classical, stat mech, and E&M.
The last thing I want to present in this section is a very clear example of the success of my student mentoring strategy: Andy, Larry, and Anthony (our three grad students) all applied for and were awarded individual research grants recently. These equipment grants were for $3,000 each, from UNM's graduate student association. Each of them drew up their own budget and individual research plan, and obviously they all succeeded in bringing in external funding for their research. They even went against my advice of combining their efforts to go for a single $3,000 award! I love that they proved me wrong, and I love even more that they have succeeded in getting their research funded at such an early stage in their careers. Each of them are purchasing specialized parts to make our optical tweezers better and they have thus succeeded in a major part of research: getting the funding so you can do the things you know you need to do. I'll end this section with a big congratulations to our grad students!
What's cooking?
Optical tweezers
We have a lot of things cooking right now, and like I said above, I think 2009 is going to be a really big year for our lab. Of course, optical tweezers construction has been a major focus. Anthony, Larry, and Linh have been working on this for over a year and achieved a number of milestones. Recently, Andy Maloney has brought his amazing optics and design skills to the project. He's also making a transition to open science, and has started publishing a lot of his work on OpenWetWare, Google 3D Warehouse, and elsewhere. Just one cool example is the current condenser / detection optics design, you can see a snapshot of Andy's sketchup design here.
Molecular biology and yeast genetics
In addition to constructing optical tweezers and control software, we've had a lot of things going on. One major area has been with our collaborator, Mary Ann Osley, working to create site-specific chromatin tethers and other biological constructs. Diego Ramallo Pardo (now at Stanford biophysics graduate school) initiated this work for us and made a lot of progress towards our goal of creating "unzippable" native chromatin fragments from a specific locus in yeast. Diego succeeded in transfecting yeast with a PHO5 plasmid having a unique I-SceI restriction site and he also succeeded in making dig/biotin DNA tethers. Further, he worked on our protocol for creating the versatile unzipping construct. This is a construct I designed during my graduate work. The beauty of this construct is that it allows for unzipping of virtually any DNA fragment that has a sticky end (see the figure). The versatility and power of this design has been demonstrated by students in the Wang lab who used the design to study helicase (Dan Johnson, preliminary work by Richard Yeh), mismatch repair protein (Lucy Bai), and mononucleosomes (Alla Shundrovsky, now Michael Hall), and of course my own work demonstrating the ability to map and probe protein-DNA interactions by unzipping.
Before he left for graduate school, Diego taught another student, Brandon Beck, what he had learned, and Brandon succeeded in creating unzipping constructs from an XhoI-digested plasmid DNA. The torch has now been passed to Anthony, who also has a strong natural talent for molecular biology. Furthermore, he's added an Open Notebook Science dimension to the project. You can find his notebook on openwetware. Anthony is focusing on creating shotgun clones from XhoI-digested DNA. We will use this to demonstrate shotgun DNA mapping of yeast genomic DNA--because we can sequence the clones to validate our single-molecule technique.
Alternative splicing: very promising simulation results
I want to update you on one specific result that Larry achieved recently: demonstrating that single-molecule analysis of splicing by unzipping looks very promising. Like all of the above fascinating unzipping studies, this too will be enabled by the versatile unzipping construct and the ability to unzip any DNA fragment with a known sticky end. We have been thinking that structural genome mapping would be a very cool application of our shotgun DNA mapping technology. (See our preprint on Nature Precedings.) Mary Ann Osley, our collaborator on our chromatin mapping project, suggested a couple months ago that we simulate an inversion mutation, since these are tricky to detect with ensemble methods, since they are "balanced" mutations. We asked around on friendfeed and got advice to check out "inv16" for acute myeloid leukemia. Unfortunately, Larry and I didn't know enough about genetics to figure out what exactly inv16 involved, and thus we couldn't easily simulate it. However, at that time, I remembered some very intersting material I had seen Scott Ness present, related to alternative splicing. It occured to me that unzipping would be perfect for analyzing splice variants, because large deletions, insertions, or rearrangements are easily detected by single-molecule unzipping. So, Larry found a recent paper from the Ness lab, about alternative splicing of c-Myb, which is the fascinating topic I'd heard Scott Ness talk about. Larry was able to find the sequence for a couple splice variants (8 and 8-b) on Pub Med, and put them into his unzipping simulation LabVIEW application. You can see the results of this simulation in the figure. Clearly, the difference between the two splice variants is one or more exons being missing in the black (variant 8) versus the red (variant 8b) curves.
We showed this simulation to the lead author on the paper, "Johnny O" a postdoc in the Ness lab. Even without explaining what the hell we were doing, he immediately saw what we were talking about. (Man I wish he was reviewing our grants!) (Johnny O is an excellent scientist, and he even has that sweet nickname, so definitely he is destined for greatness.) Our plan is to wait until (a) we have our optical tweezers going and (b) Anthony has mastered the DNA ligation method for creating the unzipping construct. Once we get to that point, we're going to get in contact again with Johnny O and see if we can develop a collaboration with him and Ness to try some single-molecule typing of cDNA clones of splice variants (using variations of our shotgun DNA mapping algorithm). The fact that cDNA clones have known restriction sites should make this experiment quite easy to try out once we have (a) and (b) going. This will be yet another example of the versatility of the unzipping construct I developed. And the fact that splice variants have large structural changes makes it highly likely we can succeed in single-molecule typing of splice variants (supported by our simulation above). I'm in love with this idea so much that I'm thinking it should evolve into a specific aim for our upcoming R01 applications. I'll talk more about that on my research blog, which I tend to use more for discussion of funding and future research plans.
So, that's my update on what's cooking now -- hopefully I've conveyed enough for you to understand why I'm excited for our lab and for our students in the coming months!
All my hopes and dreams... gone in a flash. I wanted to be the first or at least be able to establish my thesis based on this line of work. Instead that hope has been reduced to nothing. What can I do now? How can I continue? I don't want to find a new research topic. I don't want to find a new field. I don't want to start all over again. I just don't want to...
These are the thoughts that went through my head as I glanced over a poster at the Biophysical Society Meeting. The poster described establishing a force profile of RNA Polymerase and studying how it affects nucleosome dissociation. The work was being done by a grad student in a competing lab. The lab was that of my PI's (Steve Koch) former graduate lab in Cornell, the Michelle Wang lab.
I decided to read the poster after Larry had pointed out that Dr. Wang had a student poster not too far from where I was standing. Larry didn't really care to read it. I walked over and glanced. I rapidly read the title. I don't remember gathering much information from the title, but after quickly scanning the poster an image of RNAP with the transcription bubble caught my eye and urged further reading. I walked closer and read a little more. I inched closer and read more. Each reading prodded me closer and to divulge further. Finally I decided to read the whole thing and ask the student questions.
The student (whose name escapes me as of this writing) was very friendly and nice. She discussed with me what they were doing and I told her that I would be doing the same thing (or so I thought). She was very interested in the technique I would apply and I told her it would be the same as hers. I then told her I worked for Koch and she immediately recognized the name. She shot me a smile as she realized that all her work was based on his prior work (the tweezers are courtesy of he and Richard Yeh, and their anchor construct is all Koch's doing).
In reality all the fears I had were premature. Sure they were warranted. A competing lab is working on the same topic and idea that we are. Turns out they are working with E. coli while KochLab is initially working with yeast (proof of principle stuff) and eventually will be upgrading to human genome studies.
As I gazed at every single section of the poster, I pondered in both wonder and fear. Wonder because the work done was very good and interesting. I was fearful because it was all the same work that I wanted to achieve. To feel like my project was being ripped out from right underneath me could quite possibly be the worst feeling in the world. I did have other endeavors I could follow, but the RNA Pol II studies are what I am most interested in, and I truly would like to be the first to carry out those experiments.
I have learned a very valuable lesson from that experience. The fear of scooping is a very real fear. Being an open scientist, I suppose now I could fear that even more, but I really don't have it in me. I want the whole world to know what I plan to do and share my experiences in real time instead of portraying the clean cut science at the very end of it with just a paper. I in fact would like to turn this experience into a positive. After seeing some of the work that my competitor is doing I would like to see if there is a way we could collaborate. Maybe that can never be, but at least by this offer I can put my fear aside and make it a strength.
This is my second science conference ever with my first coming last year at the same meeting but in Long Beach, California (LBC). Last year was immensely fun both conference wise and extracurricularly. Outside the conference I had many adventures, and during there were so many talks I wanted to go to and posters I wanted to see that I couldn't keep my head on straight. I really had no chance of seeing it all.
This year I expected nothing less. I made no plans as far as venturing the city and left it all to chance. I tend to be that way. I like to go with the flow and make it up as I go. Don't think that I'm not organized or have any motivations, because that is just not true. I just don't like to make plans unless I have to and I like to keep my schedule free. As far as talks and posters go I have some experience under my belt so it shouldn't have been as tough as last year. I also know a great deal about my own research and the overall focus of the lab so I can pick appropriate talks and posters easier.
My feelings this year is that nothing really blew me away. I remember learning so much last year, but this year I am not walking away with that same feeling. There were some talks that I was really looking forward to just to find out that the research being presented had very little to do with what I expected (from the title). I was also a little disappointed in the quality of some of the posters I looked at.
With that said, it wasn't a total bust and there were some very noteworthy things as can be found here.
Some highlights:
The Block Lab showed why they are the best at what they do yet again. This year they cleverly attached DNA handles to kinesin motor heads to study the mechanics of the step. By using DNA fragments shorter than the persistence length of DNA they were able to use the DNA to manipulate the heads to gather force intel and other information about the stroke.
There was a beautiful talk detailing the truth about S-phase DNA. The group used specifically binding proteins and fluorescent labels to attach to dsDNA and ssDNA to distinguish melted DNA from the mythical s-phase.
The Wang poster was pretty good (about RNA Polymerase unzipping) and actually gave me hope for my project. We can also use their data as fuel to the fire for my own proposed experiments.
Meeting Micah and viewing the Williams Lab was awesome. We had a great night and learned a lot about aligning tweezers and setting them up from him. I look forward to meeting him again in the future.
Being in a city with a great public transportation system and plenty of things to do was amazing. The food was great and everything will be greatly missed when I return to boring old ABQ.
I haven't really had much time lately for fun extraneous stuff (like blogging), but I figured I have some time before I go to Boston so I might as well show something.
Larry is presenting at Biophysical society so he called on yours truly to create a bunch of graphics to accurately represent our science. Below are a few figures from the poster for your pre-viewing pleasure.
This first image quickly details my aspect of KochLab. That is the molecular biology aspect of the lab. The green blobs are yeast chromosomes, and the cleaver is a restriction endonuclease.
This next image is used to diagram the different aspects involved in unzipping DNA, namely that one has to deal with base-pairing, single stranded DNA (ssDNA), and double stranded DNA (dsDNA).
I made the next image to demonstrate how the optical tweezers will function. As you can see, the DNA is attached to a microsphere in an optical trap. This interaction is through bonding between streptavidin (on the sphere) and biotin (embedded in the DNA). On the other end, the DNA is affixed to a glass surface because of the specific binding of dig (on the DNA) and anti-dig (on the glass). This setup is made possible by the use of Koch's anchor DNA. It is created from dsDNA with a nick. The dig is on one side of the nick and the biotin is on the other. This short segment of DNA (an oligo) is ligated (attached) to a fragment of DNA that a user would want to inspect, in our case yeast genomic DNA. And that is as good a quick description of the process as you are going to get.
If you are going to be at the Biophysical Society Meeting, come check out Larry's poster (Lawrence Herskowitz) and admire our very cool science (and my sweet images).
I feel like a boy on his first date. As the whirlwind of stuff that I must learn in the coming months is quickly explained to me I wonder to myself, "This is a nice place. I can envision a continuing collaboration with these folk. I can't wait to settle down and become a more permanent fixture. I don't want to meet her dad though..." Whoops wrong side of the analogy.
I don't want to start making assumptions (I may end up hating biology), but the atmosphere is very nice. I think I just need to take it slow.
First things first, keep everything clean! This is going to be the hardest part for me to get used to. That and not dropping everything. Despite my pretty good hand-eye coordination, I am pretty clumsy. I am also forgetful which makes the sanitizing part difficult. I am organized though so that should be pretty useful.
I do have minimal experience in a wet lab setting. At KochLab, we will perform minor bio-prep for experimentation on the microscope and that I have done many times. The procedure we follow is called tethering and the protocols we employ can be found on the wiki (too lazy to link). Everything that I am currently embarking, however, is completely new. I am going to have to learn to run in this lab. It is a good thing that Kelly has decided to mentor me in the techniques needed for this project.
I hope all goes well and I do become a more permanent fixture of this lab (Osley). More to come.
I want to make a short post to point out the contributions to science members of my lab made last week. Our activities have really been ramping up, so I don't think we can keep up these kinds of updates, which is good! Here are the things I wanted to note:
- Anthony started doing open notebook science. His notebook is on openwetware. Actually he started this a couple weeks ago, but I was so used to using our private wiki that I didn't notice until this week. I think Anthony has the perfect demeanor for open notebook science, so I'm thinking this is going to work out really well. There are still problems ahead, though, especially since he's going to be working in a collaborator's lab, on totally new science to him. So there will be technical (it's tough to do wet lab and wiki at same time) as well as procedural issues (some people may not be comfortable with openness).
- Andy began posting much of the work he's done w/ Google Sketchup in his "3D warehouse." He's very talented with this application, and he's built a whole bunch of models of optical components (mostly from Thor Labs). I think these modules will be useful to others around the globe who are using Sketchup for designing optical systems. You can see one of his full designs on this youtube video. A very interesting point about that video is that he found a Sketchup model of an Olympus IX-81 microscope that another user had generously shared. Since it's pretty much the same as the IX-71 we have, it saved Andy a bunch of time--and is a perfect example of how sharing these kinds of things can speed research progress.
- Caleb also began open notebook research. His notebook is on OpenWetWare. He's only been using the notebook for the past couple days, and he's been adding notebook features daily. For example, today he implemented a feature so he can link to differences in the code he's writing. I thought that was pretty cool. Caleb has many amazing talents with computers, networking, and that kind of stuff (I don't know the correct terminology). He set up our incredibly useful and stable lab network, which includes a windows server, exchange server, VPN, MediaWiki server, ... and I don't know how many other things that I don't even know about, but which make our research so much easier. This semester, he's leveraging those talents for the purpose of creating new tools to make open science easier for us and others who use MediaWiki. For example, he's currently working on an extension to make it easy and transparent to recover any notebook data lost due to wiki problems. Another thing we're thinking about is implementing an "email to wiki" feature, which I think would be very helpful for lab workers.
This is for a small student grant. The award is $3500 or so and I wrote on some cancer related research in the field of telomeres. You can find my application (written back in October) on Scribd:
http://www.scribd.com/doc/11446505/GRD-Application
I guess I'm officially the guinea pig of the KochLab (I don't know why Koch puts a space there... it's not like it's his lab or anything). Well Koch is the real pioneer because he is the one who initiated the whole open science thing 2 years ago. If I have to guess, I would say I am the most open person to the idea. This could stem from the fact that I really have no clue how most scientists behave when it comes to research. I always envisioned a world where everyone shares what they study. In a sense that is true, but I never imagined that there would be underhandedness like scooping. Wikipedia and other internet media have fueled my ideas, but then Koch showed me the real world.
Anyways, as Koch mentioned in another post (on another blog) we've been a part of OpenWetWare (KochLab)for two years now. While a part of them for so long, we have not performed much open research. We have had our own little community on a private wiki they supplied us. That experience has been amazing. On there I have the freedom to do anything. I mean anything. I keep a lot of personal information there (which can be viewed on my personal blog). The private wiki allows me to enjoy science a little more and the fun things I do there have really helped me learn wiki-ing a lot. Some of those things I don't feel I could/should do in the public eye because it isn't of the utmost professionalism. Maybe in time I will loosen on that stance.
I started on the public wiki around the time I first joined the lab (same time I started using the private wiki). Koch warned us of some dangers of going open, and since I've kept my exposure at a minimum. I'm not saying Koch is holding me back, that's far from the truth. I just felt that since there are more reputations than my own at stake, I should be a team player and do what I think is best for us all.
My initial work involved some minor changes to the OWW logo and some random other things. I stole the userbox template from Wikipedia and added that to OWW. The Wiki-ing and the OWW logo allowed me to rediscover a passion in a new media - graphic design. After messing with the OWW logo I embarked on a mission to create the ultimate KochLab logo (hopefully soon to be added to this page). I do other graphic design too (also on my blog), but that has been put aside so that I can focus on developing my own projects. I will post descriptions of these in more detail eventually on the public site.
Koch realized that I have some talents in the biological aspects of our course of study (we all have been physics trained), and now I am joining (part time) a biology lab in the cancer research section of campus. I will publish everything I do in my notebook on OWW, and hope to bring a little open science to our friends over at UNM Cancer Research (sorry, I'm just tired of adding links). You can follow everything I do (almost daily) research wise in my notebook and I encourage you to follow our lab on OWW as well. Also check out other things that I do on my user page.
Times are changing and I'm proud I get to be one of the pioneers of it all.
Andy hasn't started blogging yet, so I wanted to put up a quick note. Andy designed and built a laser diode system using OEM parts from Thor Labs and elsewhere. Anthony and Larry helped him assemble it, and I think Linh helped with some of the latter parts too. We're going to use it with a 1 watt 690 nm laser diode for our optical tweezers (OT). The idea for doing this came from both Andy and Mark Williams, who visited us and told us that they really like using laser diodes for OT, because when the diode is shot, it's only $500 or less to replace it. The reason I'm posting now is because Andy has posted on OpenWetWare his detailed instructions for how to do build the setup. I've been encouraging him to do so, because I think his instructions could really help out a bunch of people around the globe who would like to assemble the same system. My over / under is six months before someone emails Andy to say, "Thank you / one more question:". If you take a look at the page, I think you will agree with my conclusion that two things kick ass:
- The laser diode system that he built
- Andy for writing up and illustrating such amazing instructions
Thank you, Andy!
Today, Larry, Anthony, Linh, and I hunkered down and created a draft of our first paper that will come out of our lab. We had been really struggling to write this paper collaboratively in bits and pieces on the wiki, and so we decided to just block off a bunch of time and try to write it together using Word, an overhead projector, and a whiteboard. This took us about 9 hours and worked fantastically. Pats on the back for all of us.
You can find a draft of our paper on Scribd. We welcome any comments or criticisms on this draft!
The work we are describing was done by Larry at the end of last year (2008, August and on) and we believe it presents really promising evidence that shotgun DNA mapping (SMD) by unzipping single DNA molecules will work in a variety of applications. We've been discussing the idea for over a year, particularly during Diego Ramallo Pardo's work towards single-molecule chromatin mapping in collaboration with the Osley laboratory. We had been thinking that SDM would enable single-molecule mapping of native chromatin molecules (we'll call that "shotgun chromatin mapping"), but we now envision other areas of high impact. One area would be in structural genome mapping. We cite the paper by Kidd et al. (2008) which described the amount of structural genome variation between 8 human individuals. Due to the nature of this kind of variation, it would be very well suited for detection by single-molecule DNA unzipping. Furthermore, we envision in the future shotgun DNA mapping of DNA from tumor cells, which (if someone made the method suitably high-throughput) could be a way of typing tumors based on structural genome variety. Another possibility is a genome could be scanned for protein binding sites by shotgun DNA mapping in the presence of purified protein (e.g. finding new binding sites for a newly purified protein of interest).
We're currently planning on submitting our paper to Biophysical Journal. This is a very good journal that we often read. However, we're still wondering whether we may be able to publish in a higher impact journal and reach more biologists if we can better explain the potential applications of our work. We're hoping our biologist friends will have some suggestions about this after reading our draft. And please do let us know your opinion!
(You can read more of Steve's comments about the writing process on his research blog.)
I have been in the lab for about 1.5 years and a graduate student for 2.5 years. Seems like a long time for me (maybe not so much for some grad students), and even though I am where I am now... it hasn't always been the easiest path. In fact it has been quite the opposite.
There were moments where I thought I was going to fail out of grad school. Classes were so hard. In undergrad I was used to putting in a total of 5 hours (max) a week for all my classes. Coming to UNM, Larry (the other grad student) and I realized we needed to do far more. For our first couple of semesters (Fall 06 - Spring 07) we needed to work at least 20-30 hours a week on homework. We were taking half as many classes and putting in 5 times the effort.
We even saw a decrease in our GPA. We went from being 4.0 students to getting B-'s (2.66 roughly) in ALL of our classes. Passing at UNM is a 3.0 for graduate students. Needless to say, I felt very defeated and I didn't believe that I belonged at UNM. I was recruited by Koch with the aid of Larry to join his new startup lab. This was the first turning point of my career.
That summer (2007) Larry and I did a lot of work in the lab, and had a really good time doing it all. My confidence was returned. Thanks to our awesome PI. He had so much faith and confidence in our abilities that I believed that I could survive grad school and attain my Ph. D.
The end of my first summer in the lab came the prelim exams. I had just returned from a trip to Hawaii, and Larry and I began studying at least 10 hours a day for a week for these tests. After all that work I had failed both exams I took (there are a total of four with each being in a different branch of Physics) and Larry had passed both (we studied for two). I was again feeling down. The upcoming semester brought more hardships through classes which we did slightly better in (now achieving B's and B+'s). But I still wasn't getting above the level required for staying at UNM.
Winter 08 brought my next try at the prelims. I had to pass 2 exams in order to stay here. Larry and I took the tests we hadn't taken over the summer. Larry passed them both and I felt like I did horrible. I even took a third test to improve my chances. That test I didn't study for though. Surprisingly I managed to pass one of the exams I studied for and the one I didn't. I was here to stay for at least another semester and the summer.
Spring 08 helped me by a mile. This time we did well in our classes and met the requirements (although barely). The summer came and research continued. It was full of productivity and ingenuity and all those other appropriate words that describe a lab kicking ass (sorry for the vulgarity). I had to derail myself though because I had to pass two more prelim exams.
Koch and I set up a competition to help me study. He would run 1 mile for every hour I studied. I managed to rack up a lot of hours (each week was on the order of 30 hours) and he managed to get in good shape. The prelims came. Those tests can really knock the wind out of your sails. I went in feeling really confident and left thinking that I was on the verge of a dropout. When all was said and done though, I had passed both exams and I was set to stay in grad school. My stresses (for the time being) were over!
Now I am here contributing to several places (this blog and openwetware.org to name a few) and more importantly a firm member of the KochLab.
If I can offer one piece of advice to any aspiring Grad Student it will be: Do what you can in undergrad to make sure you understand everything. Grad School will be a pain in the ass and very difficult, but once you are past the obstacles you are free to embark on the career path of your choosing. Enjoy it while it lasts because not everything is fun and games!
My name is Anthony and I am one of the first grad student members of the KochLab. I will come with news of all sorts for everyone to read. I will describe what it is like to be a graduate student and what it is that I do here. I will also be telling you some funny stories from the lab.
I come from the internet age I suppose. What does this mean? Well in science right now there seems to be 2 groups. Science 1.0 and Open Science. Science 1.0 is the old way of doing things. 1.0ists will discuss science with others, but they certainly wouldn't broadcast it out there for the world. I would fit more in with the open science crowd.
What is open science? Just think of Wikipedia. Everything known, and hypothesized is published there and anyone can come and read it and others still can contribute to the general knowledge. The KochLab are members of OpenWetWare which is a community of open scientists that want to share their research with the world. We joined because the PI (Steve Koch) wanted to be able to join the "open" world while still being able to protect himself from unseen harms as a new PI with a new lab.
We call our research interface the Wiki because we can post and edit each other's work (on OpenWetWare) just like you could on Wikipedia. We have two aspects, one is a private wiki and the other is public. As of now most of the students (and Koch himself) make great use of the private, but not so much on the public site. This is all going to change real soon...
I am going to take the leap into open science by broadcasting all my work in the public light. You can follow our lab work on our page as well as follow along here. Other lab stuff include facebook groups, citeulike, a youtube channel, and soon to be many more. You can also follow my personal life (non science stuff) on my own blog.
Posts
Waiting for flight home from Atlanta from the ARL / DLF E-Science Institute Capstone event. Overall, it was a very productive event, especially for discussions with Rob Olendorf (my collaborator and a data management librarian at UNM) and Dale Hendrickson (head of Library IT at UNM). Almost all of the attendees were library personnel, and I learned a lot from my interactions and the ideas presented. I thought I would jot down some ideas and action items.
First, action items. We were encouraged to develop "next steps" for when we return to our institutions. Here are some of ours:
1. Incorporate Library interactions with the undergraduate physics course (PHYC 308L, electronics lab) I am teaching next semester. This is a new course for me, and I won't have time or familiarity to diverge much from the very good plan that prior instructors have developed. But I know enough that Rob, Dale, and I came up with some concrete ideas that will be great for spurring data management at UNM and with these budding scientists:
- Guest lecture by Rob to describe data management and related library services. I think this would be best for the second lecture period in the course. Rob will describe issues of data management and we will announce our intention to integrate library data management into the course (below). Rob will also give an overview of github and a quick "how to."
- A substantial part of the course (as I understand from talking to prior instructors and students) involves developing LabVIEW code for circuit design and simulation. I'm guessing (pretty sure) that no source code control or versioning is used. I think this presents a good (not perfect) opportunity to teach the students how to use github for versioning and source code sharing. I'm thinking it will be an integrated requirement for all of the coding during the semester. The reason it's not perfect is because LabVIEW uses binary files, so some of the forking and merging functionality will not be appreciated. Many of the students are experienced in Matlab, though, and where possible I will encourage moving to that platform. Regardless of how this plays out, I think for sure the students will come away from the course with a fundamental knowledge of github and how wonderful it is for protecting and sharing code. I think I will also require LaTeX for their final reports, which will work well with github.
- Incorporate data management, using the Library Institutional Repository. Some infrastructure and coordination with the library will be necessary here, because I don't think we've done it before at UNM. Dale's idea is to create a "community" in the d-space IR for our course, e.g. "Junior Lab 308L." The students will be in charge up uploading their final data sets (testing their circuits) into permanent, curated objects in the IR. There may be difficulties with this, but I am confident that the students will come away with a good appreciation of the power of good data management, and, hopefully a real, curated data set as part of their career portfolio.
Next week, I am attending the E-Science Institute Capstone event, along with Rob Olendorf and Dale Hendrickson from U. New Mexico Libraries. As part of our preparation for this event, we are interviewing several people around the university to capture their views on e-research. Today, Rob and I interviewed Martha Bedard, Dean of the UNM Libraries. Rob and Dale figured it would be good to have me lead the interview, since I'm coming from outside of the library and thus would ask different questions. At least from my perspective, this was a success and I learned a lot in the generous one hour of time that Martha gave us.
At this point, I can't share the interview notes publicly, but I did want to share one idea that emerged during our discussion (and there were several good ideas!). I'm having trouble getting the idea in writing so maybe by poorly blogging it, someone else can turn it into a good idea, if it's sensible at all. Here's what I'm thinking: wealthy donors, or a group of donors that want to make a big impact on research at their university have at least the following two choices:
1. Provide substantial money to fund research in a specific field, for example by providing 10's million dollars to fund a nanomedicine research center. Or to build a new biomedical engineering building. Etc.
2. Provide substantial money (say $10 million) to the university library in order to vastly improve the ability of ALL researchers at the university to conduct e-research. The money would go towards hiring many new library faculty and staff members and procuring and implementing storage and networking infrastructure. The goal would be a completely transformed library that would make it easy and almost automatic for all university researchers to conduct connected, networked, open, archived, discoverable, etc. research.
Option 1 is common and makes a big impact on specific research fields. Performing research in excellent facilities, with dependable funding is a great thing for researchers. As far as I know, option 2 is less common, and I'm not aware of a good example. But I think there'd be tremendous leverage compared to option 1. The reason there is so much leverage is because currently the huge potential of "e-research" remains almost untapped. There are shining examples of successes. (For an excellent overview of the successes and the vast, untapped potential, read Michael Nielsen's excellent book.) But in reality, for most researchers it's really difficult to manage data, share data, provide open access publications, etc. And this is true even for researchers like me, who've decided to be as open as possible yet are finding it difficult to do so effectively! So, it's basically true that there are huge technical barriers for most of the researchers to maximize the impact of their research by sharing. Because we're so bad at it and because it's so difficult, I think there's a ton of room to make a huge impact at a university with a medium-sized grant. I think the uinversity library is the natural and only choice to lead the effort. And by doing so, it would impact all of the researchers across all of the disciplines (humanities, science, medicine, etc.). How would they implement option #2? I don't actually know, and that's a big reason why I want the library to do it! Rob Olendorf, my collaborator at UNM on open data projects has a vision for how to make it seamless and almost automatic for researchers like me to connect, archive, and share our research and data. I don't understand how that can work, and I don't have time to understand. But I would LOVE to participate in that system.
That's the final key to the idea. I think a university would gain a huge competitive advantage by becoming the "e-research leader." There is a perception that most researchers are content with limited sharing and the status quo. This may or may not be true. But regardless, it looks like there is a lot of momentum, driven by the public interest, for funding agencies to go much further with data sharing, data management, open data mandates. These mandates are scary to many researchers. Even if researchers want to have excellent data management and share their data, it's almost impossible to do so now. So, compliance will be a huge and new headache for researchers. If a university could boast that compliance is "seamless and easy" it would be a real and strong recruitment incentive. This probably sounds questionable to some, but I really see it as a huge incentive. It would be just as appealing as the opportunity to work in a fancy new research facility.
Two things have happened this week that make me really happy about the research in our lab and the spread of open science. First, we have a new undergraduate REU student, Alex Haddad, who has started her own open notebook science under the mentorship of Anthony Salvagno. Her notebook is on wordpress.com and can be found here. This is Alex's first experience in a research lab and she has immediately embraced open notebook science and she is excited about it. One cool thing that I've noticed already is that her notebook entries are automatically linked in Anthony's notebook when she links to them. Some kind of trackback thingy that I don't understand, but is great as far as good notebooks go. An example can be found in Anthony's notebook entry, which automatically links to Alex's entry providing more information (see the trackback at the bottom of the page). Welcome, Alex, to open notebook science!
The second thing that happened is that our former PhD student, Andy Maloney, just started a new postdoc at UT-Austin with Hugh Smyth. This is going to be a very productive experience for both Andy and Hugh's lab, I am confident. Most excitingly, though, is that Andy and Hugh have decided to incorporate open science into their projects! I think this is very big news and a success for the spread of open science. Major props to both Andy and Hugh for their willingness to carry out major parts of their research using open science! I had some further thoughts on this and the implications for the spread of open science. Instead of re-writing them, I'll just quote my comments on the FriendFeed thread:
I think big factors are Andy's commitment to open science and his new PI's commitment to making an impact in science and medicine. I met Hugh Smyth a few times when he was at UNM and only detected awesomeness, both in his research and in his mentoring and concern for students. Openness is probably going to be more challenging for them, though. One reason is their research is much more applied and medical, and thus IP plays a major role. The field is probably a lot more competitive. And their lab is much more successful with funding. As Nielsen and others have pointed out, the current reward system stacks the cards against openness. So they will have to be careful. But I think they're clever enough to figure out how to do it, and their success will pave a lot of roads for future openness. I've been thinking about it pseudo-mathematically and I think the fact that they're even willing to try is a success. I've had two PhD students graduate so far. One is likely in industry for a long time and unlikely to be open for a long time if ever. The other, Andy, is now at least partially doing open science. The subsequent students in our lab (Anthony, Alex, Nadia, Pranav) are still performing open science. A former intern, Diego Ramallo Pardo is in grad school at Stanford and has a passion for openness, but not able to be open yet. Dozens of undergraduate lab students have performed open notebook science in my lab course, and there have been a few instances of continuing ONS after the course (most do not continue in research careers). So, at first glance it appears that there isn't a high rate of spread of openness from our research and teaching labs. But it occurs to me that it doesn't matter. If we were to model openness as an infection, it's a powerful one. I think it's even a latent infection in almost all scientists. Participating in openness awakens the infection for life and it sheds constantly. The immune reaction is our current system of practicing and rewarding science and it's quite powerful. So it wins in a lot of cases. Nevertheless, openness is slowly winning more often and the immune system is not going to adapt to get stronger. On the contrary, the immune system is going to take major hits in the coming years. Funding agencies are going to change rules. Tenure and Promotion and hiring committees are going to add members who value openness. Closed-access publishing for profit is going to topple precipitously. And at that point, openness will spread and emerge naturally and quickly. It seems plain as day to me. Now, one of you all can translate that into epidemiological mathematics and fiddle with some exponents.
Earlier this week I was lucky to participate in the Open Access Week event at the University of Arizona: The Future of Data: Open Access and Reproducibility. The event was hosted by Chris Kollen and Dan Lee of Arizona University Libraries. I am very grateful for the invite and the opportunity to meet them, some active member of the audience, and the other speakers, Victoria Stodden and Eric Kansa.
Victoria Stodden gave an excellent talk, framed around the computational sciences, and with the major point: Instead of promoting "open data," we should promote "reproducibility" in science. She argued, very convincingly, that good science requires reproducibility and thus scientists should be easily convinced that we need very high standards for reproducible results. For computational research, the only way to ensure reproducibility is to publish much more open data and open code than is normally done now. If your result is computational, how can anyone hope to replicate and build upon your results if you haven't provided the source code and the data sets? They can't, but publications without code and data are by far the most common these days. It's a failure of science that is probably caused by many factors. One that comes to mind is that computational scientists have been forced to fit their "publications" into standard peer-reviewed articles, where the system is not set up to accept and / or host source code and data. (As an aside, this is clearly a routine failure of peer review, as referees obviously are not ensuring reproducibility of the research, which should be a primary criterion for publication.) Scientists understand that reproducibility is an essential element of research. For example, two years in a row, my undergraduate physics majors identified reproducibility as the most important element of good science (see brainstorming 2010). Since scientists understand this, then they will naturally practice open publishing of data, code, methods when they realize that reproducibility is missing without those elements. As Victoria argued, demanding "open data" leads to confusion and resistance and ultimately probably lack of compliance. In contrast, demanding "reproducible research" is already a cultural norm and it naturally leads to open data and open code of the most helpful variety for reproducibility. Victoria's slides can be found here.
The notes for my presentation can be found on linked mindmaps, starting here. (Click on the tiny right arrows to navigate.) My notes are probably not too meaningful if you weren't at the symposium. In contrast to Victoria's high-level talk about policies that could make a major impact, I told a few stories about open data and open notebook science in our own teaching and research labs, and the successful impact we've had already. I think (hope) it provided concrete example of the benefits of open science. On the one hand, I showed that open science, especially open notebook science strongly promotes reproducibility. This has been seen best in the undergraduate physics lab that I teach. Students read the notebooks of other students from prior weeks and prior years. They build upon these previous results, which allows them to get the experiment working much quicker and have more time to explore new aspects of the experiment, or to develop new data analysis methods. They are doing real science! I showed an example of an excellent primary notebook from Alex Andrego and Anastasia Ierides. However, I think I also showed that open data and open science make an impact beyond just reproducibility. This impact is in reuse and repurpose of data. I told two stories where theory and research groups already have been able to use data we publicly shared on youtube. One group has already used our data in a theory preprint on the arXiv. Both groups expressed delight and gratitude that our data was freely availalbe. There are two important features of these stories. First, both groups used our data for a purpose that we had not (and probably would not have) imagined! Clearly the impact of our data was multiplied by being public. Secondly, we did the easiest and simplest sharing method we could find: youtube, yet we still made an impact. We are currently working with Rob Olendorf, a data curation librarian at UNM to vastly improve our sharing. This will include permanent citation links, vastly improved metadata (at least 10x more than the data itself), hosting by the institutional repository (much safer than our lab server), and links to other data sets. Reason would have it that if we could make an impact with the imperfect system we tried first, then the impact will be much higher with the data shared via Rob and the institutional repository.
The final talk was by Eric Kansa, who described the amazing work of him and his colleagues on Open Context, a platform for sharing and linking archaeological data. His notes from the event can be found here. And his slides are available also: A More Open Future for the Past. Despite being far from the field of archaeology, it was easy for me to see the vast impact that Eric and his colleagues are making via the open context project. A large amount of time, sweat, and money are expended collecting archaeological data. Without opening these data and curating and linking these data, the potential impact is severely limited. The Open Context team has developed a method for collecting these data, archiving them, and linking them to other data sets. The method is very effective, and importantly requires far less work than required to collect the data in the first place. This seemed clearly, to me, a case of the huge power of data reuse and repurpose. In contrast to computational science, the power of data reuse seemed to trump the need for open data for reproducibility. This is not surprising, given how different the two fields are. But it was an interesting and somewhat confusing contrast for me between the needs for open data in computational research versus archaeology.
There were several engaged audience members. One of them was Nirav Merchant, with the iPlant Collaborative. Victoria and I were highly impressed by the computational platform that iPlant has developed already, only three years into the NSF cyberinfrastructure project. I was simply amazed and I couldn't do it justice describing it. The ability to ensure reproducibility of computational research with the iPlant platform is vast. One example is how easy it is to save an image of a virtual machine and then share this image with other users. They demonstrated this for us and it took only a few clicks and less than a minute. I highly recommend reading more about iPlant at their site linked above. The iPlant team that we met was energized, engaged, and collectively brilliant. I'd love to know how they assembled their team as they've clearly done an excellent job. I intend to keep in contact with the iPlant folks and am even hoping that I could introduce the computational platform to my Junior Lab students this year. I think the exposure to these state of the art and "open" tools will be invaluable for their future research.
Overall, the one-day Open Access Week event was highly successful for me. I met some amazing people and gained a lot of clarity in my thinking about the imperative for much more openness and sharing in science. Incidentally, maybe not coincidentally, during my flights I was able to read Michael Nielsen's fantastic new book on the untapped potential of connected, open science: Reinventing Discovery. Despite having met Michael and having heard him speak a few times, I still found the book riveting and I learned a lot. I absolutely recommend the book to anyone interested in the practice of science!
Because of our lab's interest in the biophysical effects of heavy water--both heavy-hydrogen water, D2O, and heavy-oxygen water, H2O18--I received a very friendly email inquiry today. The person suffers from a health problem and currently hopes that drinking deuterium-depleted water will help with that condition.
As a scientist and a health consumer, I am maximally-skeptical of any medical claims related to drinking deuterium-depleted water. This is despite that fact that I think there's a good chance that cells may behave differently if deprived of deuterium, which exists in all natural water sources. The reasoning for my skepticism is very straightforward. There is a dearth of any published scientific or medical research utilizing deuterium-depleted water. As I will note below, there are less than a dozen research papers on the topic. So we really don't know. There is almost no evidence. We don't know whether drinking large quantities of deuterium-depleted water will be helpful or harmful or negligible.
There is much more evidence, though, that the quantity of water that would need to be consumed is quite large. Because deuterium is natually-occurring, there's a lot of it in your body! It would take a long time of drinking lots of D-depleted water to have a systemic effect. My interpretation of the existing evidence is that by far the most likely outcome of this therapy is that it will generate profit for whomever is selling the D-depleted therapeutic water.
Because I think it's a shame that a Google search for "deuterium-depleted water" is overrun by claims of cures for horrible diseases, I asked the person who wrote me if I could send my response on my blog instead of privately. So that perhaps our discussion could benefit more people. The person kindly agreed and so I will post his email:
Dear Steve,
I enjoyed reading your blogs and noted that you work with D2O.
I have a medical condition that I want to treat with alternative methods - one of them is drinking "light" water.
Do you know, or can you suggest any resources for the following:
1. how to make "light' water, with D2O concentration of below 50ppm 2. who does D2O concentration testing in the us for water samples 3. who makes light water (for sale) 4. any scholarly literature on this topic...
Any info will be much appreciated and shared with fellow friends who are in need.
Thank you very very much!!
Dear ___,
Thank you for your kind message. I am sorry to hear of your medical condition. I am not an expert on the medical effects of deuterium-depleted water. In fact, I am not aware of any medical experts on this topic. As a scientist, I am maximally-skeptical of any claims of currently-known medical benefits of drinking deuterium-depleted water. I'm not saying it will help or hurt you, I'm saying that I don't think anyone is close to knowing whether it will be helpful, harmful, or negligible. There is almost no published, rigorous research on the subject (your question #4), and thus any claims are probably speculation. I would suggest talking to a medical doctor, which I'd guess you've done plenty of, since they know almost infinitely more about the human body than I do. However, I would think that any medical doctor, or indeed any living person, would merely have to guess, because I do not see any experimental evidence beyond just less than a dozen published reports which have yet to be challenged or supported.
Below I will put responses to your specific questions, and I wish you the best,
Sincerely,
Steve
1. I don't know of an efficient method for producing mildly-deuterium-depleted water. The deuterium-depleted water we use in our research is much more depleted. We obtain it from Sigma, a chemical supply company, and it is roughly $100 per 100 milliliters (a few ounces). As you may know, you would probably need to drink a lot of water over many days to appreciably deplete deuterium from your body. This would surely be expensive. And like I said above, as far as I can ascertain, it's unknown whether it would be helpful, harmful, or negligible.
2. I don't know who does D2O testing. I'd be skeptical of anyone offering these services related to this medical purpose. Incidentally, deuterium-rich water is inexpensive. You could easily mix D-rich water with regular water and see if the purported D2O-testing company is able to correctly discern the difference.
3. We so far have only purchased from Sigma. See for example product #195294.
4. I have read two scholarly papers on the subject, both from a research group out of Hungary. I found both papers very interesting, but I also am highly skeptical of the interpretation of their results. A good place to find scholarly papers related to biology or medicine is on Pub Med. This link will hopefully take you to a search for articles related to deuterium-depleted water. I can only see one that is freely available. Google Scholar is another place to search, but it will not be limited to biological articles.
I actually find this topic fascinating, as far as whether life has evolved a beneficial use for naturally-occurring deuterium. We have a side project in our lab to see whether we can notice any effects on tobacco seed growth. We're using tobacco seeds because they are tiny, so we don't need much water to see an effect. We got this idea from Gilbert N. Lewis, who did the initial studies in the 1930's that showed that too much deuterium affects life. One of the reasons I find this side project on deuterium-depletion so fascinating is that I see it as an open mystery. That correlates well with my skepticism of claims related to therapeutic effects of drinking light water.
Below, I will embed a comment thread from FriendFeed, and also there are potential comments on the blog itself. I expect them to be a mix of helpful and derisive...hopefully more of the helpful type!
Over the winter break, Andy Maloney and our lab enjoyed an open data success story. Andy shares his data publicly with a CC0 / public domain license. Some scientists ran across the data, I think by Google searching and contacted us to ask if they could use our data to support their research. Since it is CC0, they didn't have to ask, but like most scientists, they were courteous and did contact us. I shared this story at the ScienceOnline2011 "Data Discoverability: Institutional Support Strategies" session and I think people liked the story. Jean-Claude Bradley mentioned it in his blog summary of the conference, and Lucy Power saw this and contacted me for more details. Lucy's is studying e-Research for her Ph.D. dissertation topic. I sent her a reply, and instead of rewording it, I will just past it below. I can answer questions on the FriendFeed thread. Yay Open Data!
Hi Lucy – I definitely should write up a blog post about it and I will try to do that soon. I think it’s a great little success story for open data and data reuse. In a nutshell (and I can answer questions): Some people found Andy’s microtubule gliding assay data on youtube and emailed us to say it was very interesting to their theoretical work and could they use our data in a pre-print. We replied “of course!” “woo hoo!” and we told them that it’s all public domain data so they are free to do whatever. As a courtesy, we said we’d like a shout-out. They went further and offered co-authorship, but Andy and I decided an acknowledgment was more appropriate at this time. Andy suggested they acknowledge open notebook science, etc. and they did in their pre-print. You can find the pre-print here: http://arxiv.org/PS_cache/arxiv/pdf/1101/1101.2225v1.pdf see Figure 3A for Andy’s data and the acknowledgments section.I think it’s a great success story because (A) they never would have known about our data if it weren’t open. It didn’t necessarily have to have an open license, but it needed to be discoverable. (B) we never would have thought to use our data for this purpose. So obviously value was created via openness.
OK, I’ll try to write up the story in a blog or something soon! (Maybe I should just post the above and not worry about wording it better? J )
--Steve
The award was given to Andy and our lab for our commitment to open science. This includes open notebook science, open data, sharing protocols, designs, etc. Andy has been a very impressive open scientist. It's just a guess, but I'd say so far, probably his biggest impact has been with the very detailed "do it yourself" biology projects he's contributed. He's absolutely amazing with designing solutions from off-the-shelf components, and equally amazing with using Google Sketchup and photographs to describe the designs to the public. A good example is his microscope objective heater, which was somewhere around $500 and is working very well for our gliding motility assays.
There are now many labs around the world deserving of this award, and it feels really good to receive it. And I think it was a great contest for Addgene to sponsor. I actually wasn't aware of Addgene before Andy told me about the contest. So just learning about them made the effort worthwhile. I had a great conversation with Melanie Herscovitch on the phone a few weeks ago and she explained to me Addgene's mission and services. Here's a picture from their website to explain what they do: (used without permission! :) )
In a nutshell, addgene is a non-profit organization dedicated to making it easier for researchers to share and obtain published plasmids. Authors of papers submit their plasmids to Addgene (either purified DNA or transfected cells, as I understand it). Readers who would like to obtain the plasmid contact Addgene, and Addgene provides the plasmids for just a cost-recovery fee. This works out well for all parties. Without Addgene, it's often a very inconvenient process. The authors are burdened with keeping track of plasmids that may have fallen out of use. And researchers requesting the plasmids often face a long delay in obtaining them. I think Addgene is a wonderful service and I look forward to working with them as we create and publish our own plasmids in the coming years. I also got the feeling from talking with Melanie that Addgene is a really great place to work. I don't know whether or how often they're hiring, but you can take a look here for current job openings.
Thanks again, Addgene! If you're reading this, it'd be great to post a little thank you comment (on friendfeed or the blog) or congratulations to Andy!
FriendFeed Thread:
I'm off to the Biophysical Society meeting tomorrow morning, and a bit out of steam, so I'm going to cop-out a bit and just embed a mindmap of my notes from the meeting. Before doing that, I'll post a few action items from the meeting, and maybe later I'll come back and link to specific friendfeed or other threads for the items:
- Antony and I made some progress discussing our athletic challenge to raise money for asthma research or other charity. I think it's promising we can make it "generative," and successful.
- Pete Binfield used Heather Piwowar's PLoS ONE paper as an example. I want to read it and then rate it.
- Improve our lab's Open Notebook Science. This is ill-defined, but there are many steps we can begin taking immediately to work towards a system that works for us as well as it does for Jean-Claude Bradley and his students / collaborators.
FriendFeed comment thread:
1. I had a ton of fun interacting with a bunch of e-friends, old and new.
I attended as a scientist with an interest in all of the other areas. It was definitely a new feeling to be in a session and have the speaker ask, "how many of you are scientists?" with the answer being a very small fraction of the participants in the room. It was also a very new and thrilling experience to finally meet in person many people I've known only virtually for the past year. I think Cameron Neylon was the only person I'd met in person previously. Despite that fact, it was incredibly easy to have conversations during lunch, between sessions, and of course at the bar. I uniformly enjoyed these people even more in person. An incomplete list of the people I had the pleasure of chatting with include: Bill Hooker, Jean-Claude Bradley, Pawel Szczesny, Walter Jessen, Christina Pikas, Hope Lehman, Peter Binfield, ... Plus I found some completely new friends at the conference, including Antony Williams, Greta Munger, Dorothea Salo, Andy Farke, Natalie Villalobos, Michael Habib, Annie Crawley, ... Now, those previous two sentences could be perceived as egregious name dropping, which I am guilty of, simply because it's quite an amazing list of people, none of whom I knew before I became active in open science. Clicking through those names and reading what they're saying, and you'll realize why I feel so lucky to have met them!
(Note, I forgot: Fabiana Kubke, ...)
2. Antony Williams and I made some kind of running challenge.
I knew of Antony Williams from his ChemSpider fame. I also had recently read one of his personal blog entries, about running 1000 miles in a year, along with his ugly and unfortunate calf injury. I'm not sure I knew these were the same person, though. Nevertheless, he walked passed me in the hotel bar, and I accosted him to inquire about his calf injury. I'm pretty sure he didn't know me at all, but luckily we had on slick name badges and I was surrounded by credible people. It'd be a big challenge for me to recount the conversation (I swear I remember it perfectly, I just don't feel like writing it down). Let's just say that I was happy to learn that he'll be back running again within a week or so and that he has a goal of raising money to fight asthma. I have had an idea mulling in my head that I could raise money and get motivated to get better at running by setting a race time goal. I thought this was a perfect match with Antony's goal, so I quickly challenged him to a running competition. He quickly agreed (fearlessly) and I tweeted/friendfeeded it to lock in the deal. Over the next week, I'll see if I can clarify the challenge and I'll post updates to that thread. I'm thinking I'll setup a Google spreadsheet for me and others to place their pledges and monitor the progress. Antony already knows about Nike+ technology, and I'm looking forward to doing something like that too. It'd be a good way to try out new things in open data, and open notebook science, actually. Suffice to say that I'm going to get better at running, lose a lot of weight, and hopefully we'll raise some money too!
3. I and KochLab are going to get better at doing Open Notebook Science and sharing data & software this year
I learned a lot at the conference about tools that exist for carrying out open notebook science and sharing data, methods, software, etc. I still have a lot to learn, and indeed many tools still need to be developed. But I know that our lab can make improvements this year. Here's some concrete things that we'll do:
- I've sent an email to Amy Jackson, Digital Initiatives Librarian at UNM, requesting a meeting. I had briefly spoken to her via email in October and now I'm fully energized to have a meeting with her and see what kinds of first steps we can take towards building a partnership between the library and our lab in terms of sharing data and conducting open science. I'll try to leave updates on this FriendFeed thread.
- Get better at sharing software. Currently we use LabVIEW, which is a wonderful programming environment. One of the major benefits is that it's a graphical, data flow language. This makes the code a 2-dimensional diagram...so in my opinion, it's exceptionally easy to read other people's code. Unfortunately, it's a proprietary and expensive coding environment. You are allowed to compile .exe and .dll files for others to use freely. But that's not open source. So, there are two routes to go: (1) We could compile virtual machines (VM) and send those to people for exploring our code. For example, referees of papers we submit. This was an idea from Deepak Singh at the meeting. Licensing is an issue here, and what I'd like to do is find someone at National Instruments (creators of LabVIEW) and discuss what can be done to serve our open source needs. (2) Learn a text-based, freely available language. I think this would be valuable for our students anyway, in terms of building their resumes. While at the meeting, I thought Ruby was a good idea, but now not so sure. I've posted a FriendFeed message about this, and have received all kinds of very valuable advice.
- Adopt techniques to make it easier to capture our workflow in the lab. OpenWetWare has innovations coming up soon and we'll certainly jump on those. Cameron also hinted at something revolutionary coming up this year, but said he'd have to kill Bill if he told him what it is. It wasn't clear that he'd have had to have killed others in the room, so I was disappointed he didn't say what it was. (Just kidding, Bill!) But the fact is, I don't think our current tools are nearly sufficient. I'll put in more effort to make positive steps here, but I'm not sure exactly what yet.
I was delighted to have the opportunity to talk with Peter Binfield at the bar and discuss publishing ideas with him. I have a lot of ideas that I'd like to try out, and it hasn't yet been proven that all of them are lousy. I ran many of them past Peter and his general response was, PLoS ONE would love that -- it's just that whatever scientific community you're in may not respect it. Very true. However, I do think many in my community would respect anything that showed how publishing could be better by being different. And I now realize that PLoS ONE is a very good platform for trying out a few things.
- At lunch with Bill and Pawel, they mentioned an idea that others had been talking about. Unfortunately, I don't know to whom to attribute the idea. (Note: Bill and Pawel give attribution to Fabiana Kubke, which sounds right to me now.) The idea is that publishing one very good figure would be a good idea. I like this idea enough to think about trying it out. It is related to an idea Larry Herskowitz and I were discussing a few days before the conference: Can we publish a paper without an introduction? Or an introduction that just says, "see such-and-such other paper for introduction?" So much time is wasted rewriting introductions (in my opinion), especially when trying to avoid copying prior written work. Is this necessary? Publishing a single figure takes this even further. I have some interesting data from grad school and postdoc that I have not been able to publish. It pains me that it's just sitting around, useless. Do you think it's worth using this data to test out the "publish one figure" method? If I make progress on this, I'll post updates on this FriendFeed thread. (Note added: Cameron Neylon reminded me that BMC Research Notes may be a better venue than PLoS ONE for this.)
- For maybe ten years now, I've thought that the value of anonymous peer review is overstated. During that time, I've heard other people, much more eloquent than me also express this opinion. Just briefly, I think fully-attributed, non-anonymous peer review would solve many problems that exist with today's science, and I discussed this a bit at the meeting. Two of these problems are: (a) good referee work is difficult, and good referees are not credited for the work and the original ideas, and (b) a whole lot of incomplete and sloppy work is submitted and much of it is published due to ineffective referees / editors. The solution I like is for every aspect of the peer-review process to be published, including the original manuscript submitted, all subsequent revisions, and all communication between authors, editor, and referees. Clearly this solves problem (a). As for problem (b), people often say, "but people aren't going to say negative things if their name is on it!" First of all, that's not necessarily true. Secondly, referees have the option to decline without comment. If the editor cannot find someone willing to slam the paper, then it's just returned to the authors. Voila! One less crappy paper published. The arguments get more complicated, especially when considering that grant review is anonymous, providing a lot of opportunity for underhanded retaliation. I can't mathematically prove that it's a good or bad idea, so I'd like to try it out and see what happens. It occurs to me that I could submit a manuscript to PLoS ONE and request that the Academic Editor implement this idea. Why not? Should be OK as far as I understand the rules. I don't expect to submit garbage, so it won't be a complete experiment. But something may be learned, and at least all the referees will get credit. I may update progress on this idea on this FriendFeed thread.
Andy Maloney, a Ph.D. student in our lab, recently read and summarized a very interesting paper in his open lab notebook. The paper, "Taxol Crystals Can Masquerade as Stabilized Microtubules," was published in PLoS ONE in January of 2008 by Margit Foss, Buck W. L. Wilcox, G. Bradley Alsop, and Dahong Zhang1. Since our lab is now heavily involved in experiments involving kinesin and microtubules, and because it addresses something that had been a mystery to us, the paper really caught my interest. I'll explain more about that below. But before doing that, I wanted to talk about something probably of more general interest: a success story for publishing in PLoS.
Andy noticed that in their methods they defined BRB80 as having 4% glycerol. Glycerol is used to promote tubulin polymerization, and I've never seen it included in the BRB80 (aka PEM) definition. It could also affect solubility of Taxol, so it's an important detail whether or not a substantial amount of glycerol was in their standard BRB80 buffer. I strongly suspected that this was just an oversight by the authors...and I could easily have assumed this and moved on. But what about future readers of the article? Was there anyway to correct that article? For most journals today, even in the year 2009, the answer would have been, "no." However, this is no ordinary journal, this is PLoS ONE! All I had to do was select the text in question, and then click to add a note. After adding my note, an icon appeared in the article, allowing any future reader to see the question.
I don't know whether authors are notified when their article is commented on. (If not, it would be an important feature for PLoS to add.) So, I sent an email to the corresponding author of the paper (D. Zhang) pointing out the question. In less than a day, D. Zhang wrote back saying that he'd asked M. Foss to look into the issue. And then again in less than a day, Margit wrote me back to say that she'd looked at the original lab notes and indeed they'd made a bit of a typo in how they described BRB80 in their report. She added a very clear response to my note. She also went out of her way to point me to two subsequent papers that have extended their taxol microcrystal research2,3. These authors deserve a lot of praise for responding to this question so quickly! A few months ago received a similarly rapid response from authors of another PLoS article...only two data points, but I wonder if PLoS authors are indeed more likely to respond quickly to questions from readers?
Now, why am I so happy and why do I think this is a success story for PLoS? It's because now, for the rest of time, when readers of this excellent paper do look into the methods, they will be able to see the corrected definition of the buffer used. Given how many times I've been burned by incomplete or incorrect methods, I do believe this will save substantial amount of time for at least a couple people down the road. (Will the PDF version of the article ever incorporate this note? As it stands now, I don't think it does...it would be very valuable if technology could be worked out to include links to these comments in future PDF downloads.) One more thing: I just noticed that Margit Foss today also posted a new comment on her article. She links to the two papers she'd told me about in her email, as "Relevant references on Taxol crystals." This is a great service to readers, especially since the newer reports2,3 support a different mechanism for Taxol microcrystal / fluorescent tubulin binding. In summary, many thanks to PLoS for this wonderful journal and to these authors for their dedication to excellent science!
Now, if you're still reading, I'd like to also comment on the very interesting science in their report. Taxol (generic name is paclitaxel, I think) is a drug used in cancer chemotherapy. It's proposed mechanism of action is to inhibit mitosis by stabilizing microtubules in the spindle apparatus. In vitro, Taxol dramatically reduces the rate of microtubule depolymerization. Many people, including kinesin researchers in our lab, leverage this microtubule-stabilizing effect by adding Taxol to microtubule-containing solutions. What I learned from the Foss et al. paper is that the concentration of Taxol typically used in microtubule gliding assays (10-20 micromolar) is far above the solubility limit of Taxol (somewhere around 0.8 micromolar in aqueous solutions). Furthermore, they show that Taxol forms microcrystals above this solubility limit (even at 0.92 micromolar) and that often these microcrystals form a striking resemblence to microtubule bundles and asters! DIC images of these microcrystals (formed in absence of tublin) are shown in these images from Foss et al.1:
(scale bar 10 microns)
The final piece of crucial information provided by this article is: these Taxol microcrystals rapidly bind fluorescently-labeled tubulin! (Later reports indicate that it's the fluorophore, not the tubulin that is binding to Taxol2,3.) This means that many kinesin researchers (including me) likely have Taxol microcrystals in their samples, and because they become coated with fluorescent tubulin, there is a huge risk of misidentifying these structures as microtubule structures. Indeed, here is a recent fluorescence microscopy video that Andy took of something that at the time was a mystery but which we now know is likely a Taxol microcrystal decorated with rhodamine-labeled tubulin!
Likely Taxol microcrystal in kinesin / microtubule gliding motility assay (using rhodamine-labeled tubulin). Andy Maloney data.
In my past, I've also often seen these structures which I attributed to "clumpy" or "weird" microtubule structures. For example, I often noticed very bright, thick, and stick-like structures that I called "microtubule logs." It never occurred to me that they were Taxol crystals! (Also I remember that these structures were much less prone to photobleaching. I wonder if that's because (a) there are buried fluorophores inside the crystals, protected from oxygen, or (b) even on the surface of the crystals, Taxol somehow protects fluorophores from photobleaching?)
Foss et al., go further and speculate on whether this has important implications in vivo (i.e. in cancer chemotherapy). I can't really comment on that, but it's interesting to think about. What's most important for us is that we now know we have a problem with our buffers (too much Taxol!) and we may be able to fix it. The concentration of tubulin that we typically use is about 0.4 micromolar of tubulin dimers. Thus, for a 1:1 ratio of Taxol to tubulin dimers, we'd need 0.4 micromolar starting concentration of Taxol, which is below the solubility limit. There's at least two things I don't know: (a) What is the binding affinity of Taxol for microtubules? and (b) Do we need a 1:1 ratio to get significant stabilization? If the answer to (a) is something like a few nanomolar, then we may be OK with something around 0.5 micromolar (500 nanomolar) Taxol. If not, then we may have to hope the answer to (b) is "no."
A quick search just now yielded a paper from 1994 that says the binding constant for taxol to microtubules in 10 nM. That'd be good, except that they also seem to say that they only get stabilizing effects when the concentration is in the micromolar range4. Dang! Well, it shouldn't be too hard to try out 500 nM Taxol and to see whether MTs are reasonably stable. It's possible our MTs may be more stable than those used in the Caplow et al. study. It's also possible that the Taxol microcrystals are not affecting the kinesin activity in our system, and that we can do our studies at high Taxol concentration. Even if so, it's great to know about this issue so we can keep on the lookout for Taxol problems.
References
1. Foss M, Wilcox BWL, Alsop GB, Zhang D (2008) Taxol Crystals Can Masquerade as Stabilized Microtubules. PLoS ONE 3(1):e1476. doi:10.1371/journal.pone.0001476
2. Castro, J. S., Deymier, P. a., Trzaskowski, B., & Bucay, J. (2009). Heterogeneous and homogeneous nucleation of Taxol crystals in aqueous solutions and gels: Effect of tubulin proteins. Colloids and surfaces. B, Biointerfaces. doi: 10.1016/j.colsurfb.2009.10.033.
3. Castro, J. S., Trzaskowski, B., Deymier, P. a., Bucay, J., Adamowicz, L., Hoying, J. B., et al. (2009). Binding affinity of fluorochromes and fluorescent proteins to Taxol™ crystals. Materials Science and Engineering: C, 29(5), 1609-1615.doi: 10.1016/j.msec.2008.12.026
4. Caplow, M., Shanks, J., & Ruhlen, R. (1994). How taxol modulates microtubule disassembly. The Journal of biological chemistry, 269(38), 23399-402. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7916343.
Foss M, Wilcox BW, Alsop GB, & Zhang D (2008). Taxol crystals can masquerade as stabilized microtubules. PloS one, 3 (1) PMID: 18213384
Link to FriendFeed discussion thread.
I just finished reading and commenting on a PLoS One article that is near my own field of research. The article is titled, "Dissection of Kinesin's Processivity." The authors are: Sarah Adio, Johann Jaud, Bettina Ebbing, Matthias Rief, and Günther Woehlke. You can see my rating and overall comments here. (Since I'm not sure if that link will work, I'll also repost my comments below.)
Throughout the process of reading and commenting on this article, I learned a lot more about my fears and barriers to PLoS commenting. I discussed some of these in my prior post about my first PLoS rating. In contrast to my first rating, this article is smack in the middle of my field of interest (the kinesin molecular motor). I deliberately chose the most relevant PLoS article I could find. I'd estimate that my fear of placing comments was at least 10 times higher than for an article outside my field. I definitely felt like my comments were piping directly into the author's email inbox, ready to enrage them at any misunderstanding or criticism I posted. I still feel this way and am a bit worried. My worries are probably justified to some extent, since I am very new to this field. Thus, I could easily be seen as an ungrateful newcomer who hasn't paid his dues. And of course the people who wrote the article could end up anonymously reviewing my own papers and grants.
Given those worries, I came close to deciding not to post my rating. However after much reading and thinking about their results, I felt compelled to make a serious comment about error analysis supporting one of their conclusions (not their major conclusion). I was confident that my criticism was fair, and convinced myself that posting the comment was the right thing to do--perhaps I can save another reader a lot of time, or even help the authors out if they read it. I posted my criticism directly in the article, along with several typo corrections. After doing that (late last night), I realized that if / when the authors DO see my comments, they'll see a string of petty typo corrections and then this criticism, but nothing positive at all. That's a problem!!! Because of this, I decided to sleep on it, and compose an overall rating with positive comments today. I was busy most of the day, but finally tonight was able to finish my rating. In all honesty, though, without having travelled that slippery slope of commenting, I don't think I would have posted this rating tonight. I would have balked at the risk of angering the authors, sticking my neck out, and possibly being wrong. I probably would have convinced myself that these risks outweighed any meager potential gain that the world of science would get from my remarks.
I'm a bit worn out now. Hopefully in the comments here or more likely, on FriendFeed, we can talk about these things. I hope in the next couple days to expand on my review of the paper in my research blog, and to include it as my first Research Blogging attempt.
Reposting of my rating and overall comments on the article
This is what I submitted to PLoS as my rating:
Insight: 4 stars, Reliability 3 stars, Style, 4 stars.
The authors recently characterized NcKin3, which is the first known,
naturally dimeric but non-processive and plus-end motor. In this
report, they are leveraging this discovery to study chimeric constructs
between NcKin (a dimeric, processive Kinesin-1 motor in the same
organism) and NcKin3. They make two different chimeric constructs: one
with the head of NcKin and the neck of NcKin3, and the other with head
of NcKin3 and neck of NcKin. Importantly, the head included the core
motor domain AND the neck linker region.
I congratulate the
authors on a lot of very nice work that must have been very difficult!
The results they report come from an impressive array of difficult
assays spanning single-fluorophore position tracking, single-molecule
bead motility assays with optical tweezers, gliding assays, and a
variety of ensemble biochemical assays.
Study of the two
chimeric constructs, in comparison with the NcKin and NcKin3 wildtypes
allowed the authors to gain insight into which parts of the kinesin
motor are important for conferring processivity onto dimeric
constructs. (And also, which parts are important in NcKin3 for
inactivating one of the heads.) As far as I know, these are the very
first two chimeras created between these two kinesins and thus open the
door for many more investigations into how processivity is regulated in
the motor domain, neck-linker, and neck regions. The results here
indicate that many more chimeric structures and site-directed
mutagenesis studies will be necessary and valuable. Of course, that is
a lot of work, but the results here open the door for those further
studies.
For me, the most fascinating result was point (iii) on
page 4. The authors show that the Head3/Neck1 construct seems to get
stuck in a "kinetic dead end." As they say, the kinesin-1 neck appears
to confer some elements of processivity, but not all. Combined with the
missing elements (which kinesin-3 head lacks), the motor is actually a
bit more handicapped, as shown by a gradual decrease in gliding
velocity as the concentration of motors is increased.
I also had a couple questions about the paper that I noted previously (see prior article comments):
* Statistical significance of processivity measurements.
* Lack of discussion and comparison with previous Ncd/Kinesin-1 chimera results
DISCLOSURE:
Our lab (http://openwetware.org/wiki/Koch_Lab) has recently obtained
major funding to study kinesin. I do not think we have competing
interests with these authors or the work they've presented here, but I
thought it worth mentioning.
OK, now that I have you defiantly reading my blog, intent on garnering something useful from it, to spite me, let me continue. The "Do What You Love" essay resonated with me very strongly. It reminded me of the discussion of talents in "First Break All the Rules" by Buckingham and Coffman. I think Graham and Buckingham and Coffman are talking about the same thing: that finding work you love is a key to happiness (and productivity), but that finding out what you love is a very difficult task worth working very hard on. The language of Buckingham and Coffman is to talk about finding one's "talents." I've been talking with my graduate students about this a lot for the past six months. (In fact, it's time for me to have another awkward talent-finding session with them, I do believe!) I also preach to all of my undergraduate students about the importance of finding their talents and I give them an end-of-semester assignment to think about their talents. I'm delighted to have been shown the Graham essay, because I think it is yet another way of presenting this argument to students, and a very eloquent one.
Since I loved the essay so much, I sent it to my father in law, Rodger. He's the one who gave me the First Break All the Rules book along with all kinds of life advice during the years I've known him. He wrote back to me and keyed in on the "always produce" part of the Graham essay:
"Always produce" is also a heuristic for finding the work you love. If you subject yourself to that constraint, it will automatically push you away from things you think you're supposed to work on, toward things you actually like. "Always produce" will discover your life's work the way water, with the aid of gravity, finds the hole in your roof.
While reading the note from Rodger, the Do What You Love essay finally clicked with another I read by Graham last weekend, "How to Make Wealth."[1] It's another fantastic essay that I feel like commanding you to read. One premise in that essay is that people in start-up companies can be 20-30 times more productive than they can in an ordinary 9 to 5 job. Thus, a small group of people can create a tremendous amount of wealth by working really hard for a few years. They can also get financially rich as a reward for their production of wealth for the world. The thing that clicked for me is that you cannot make the world a better place without producing. Most people are producing at a rate at least 20 times less than they could be producing, if they found what they loved and were able to do it all the time. I garner great optimism from this fact that we're on average so incredibly inefficient. It means most people are not even close to any absolute point of diminishing returns, and with the right kinds of changes, they could easily multiply their productivity and impact on the world by manyfold.
So, then I started thinking about our research lab and the students in our lab. I thought over things that each student has done in the past year that made me profoundly happy. As I thought over all these things, I realized they had a common theme: I was recalling instances of those students being unusually productive. Furthermore, my favorite recollections involved those where the students had shared their work on our public wiki, or our blog, or in some other fashion open to the world. This made me think that it is now very easy for me to summarize my main expectation and goal for my students: "always produce," borrowed from Paul Graham, of course. My students like to make Kochlab slogans, so I thought of "Kochlab: Produce" or "Kochlab: Always Produce," but if you pronounce the "Koch" correctly ("Cook"), then it has the problem of making one think of produce the noun, e.g. apples and bananas. Thus, I am thinking something like "Kochlab: Contribute" or "Kochlab: Always Contribute."
In some sense, "always contribute" means the same thing as "always produce." The point of the producing, in regards to Graham's essays is that you're creating wealth, and therefore contributing something to society. However, I like "contribute" much better, because it has much more clarity in the science world. "Contribute" automatically points the way towards open science (aka Science 2.0). Whereas, production in the traditional scientific world ("closed science") can be done with a very limited amount of contribution.
I have mulled it over for a couple days now, and I think I really like this as the main piece of advice and constant guidance to give to our students: "always contribute." Does this work? Let me try it out in a few ways:
1. By the time the students get their Ph.D.s, I want them to have learned a tremendous amount about what their talents are. I want them to clearly see what the next step in their career should be in order to leverage those talents and help them be successful and happy. A compass of "always contribute" will lead the students towards finding ways of being productive instead of spinning their wheels. These activities will be the means by which the students and I discover what their talents are. This is the point of Graham's "always produce" advice. Check.
2. By the time the students get their Ph.D.s, I want them to have a strong and large professional network of people that know them and the work they have done. "Always contribute" tells them that Open Notebook Science is a good thing to do. Sharing code, design drawings, personal summaries of research papers, tips and tricks on protocols -- these are all ways to contribute. In our limited experience in our lab, we have received validation after validation after validation that open contributions get attention. We can see this vaguely via page views or Google search rank or quite vividly via positive feedback from people that we admire and people whom we've helped. Combined with traditional publishing (also a contribution) and attending scientific meetings (contributing), I think "always contribute" will make building a powerful professional network almost automatic. Check.
3. I want our lab to produce innovative, exciting, and high-impact scientific results. Will "always contribute" point us in the right direction for this goal? Does it point in any direction? I need to think about this one some more. I feel like it must point in the right direction--for example, innovations are contributions. But there's some risk that focusing on contributing could lead towards a lack in overall production. Basically I am thinking of the standard arguments against open science -- increased likelihood of scooping, which in turn reduces chances of funding and publishing. I fundamentally believe that those arguments are strong enough to tip the balance, but I don't think they've been proven yet. Another example of how "always contribute" may be counter to our lab's scientific productivity: some students may discover that they are wickedly talented at contributing in ways that do not advance their research projects. That's a great thing to discover! An example that hasn't happened in our lab yet would be for a student to discover that they're fantastically talented at writing popular science articles and want to do so at the expense of doing any research. I want students to discover something like this. It fits perfectly with items 1 and 2 above. However, it is clearly a problem in regards to item 3. This is not a new problem, though. My job as a research professor is to both mentor students as well as ensure production of research results. The way the system is set up those goals are not always aligned, and sometimes in conflict. It's possible to be rewarded with research grants, even by abandoning the best interests of your graduate students. Most people in the system know this and have seen the devastating results it has for too many Ph.D. students. I am absolutely against doing that and despise many people who have chosen that route. On the other hand, I don't have a good idea about what do do if "always contribute" turns into "I can't do my research." That's definitely going to happen eventually. In many cases, it will be possible for the student to discover their true calling in life, but then re-focus on making the research contributions necessary to finish the Ph.D. that they've invested so much time in. Will there come a time when the student should rightly choose abandoning the Ph.D.? Ugh, this is a tough one: Item #3 gets an: almost check / need more thinking.
I've painted myself into a corner now. If I were Paul Graham, I would figure out a way to backtrack. But I'm not, and I don't really know how to end this blog post, so I think I'm going to end it by linking to another Graham essay about writing essays. This one was linked to me by Kartik Agaram on friendfeed. It's an essay that explains why high school and college writing assignments sucked so badly. If you hated those assignments but never quite knew why, you'll love this story. Plus, you'll feel vindicated and it will give you one more reason to trust your gut in the future. For example, if your gut were telling you that "always contribute" is a fantastic compass to present your graduate student mentees.
Footnote:
[1] I'm taking a bunch of liberty here with my own story. It wasn't until I started writing this blog that I realized the two essays had clicked. But I think subconsciously this is what was happening. Also, I probably had the Gin, Television, and Social Surplus essay by Clay Shirky in my head, as Joelle Nebbe had linked to it recently.
5/27/2009 SJK Note: After I wrote this, Bora Zivkovic sent me links to the PLoS community blog where he talks about commenting and rating PLoS articles. Both are very much worth reading! Bora is the Online Discussion Expert for PLoS.
Recently,
So, tonight I made my first comment on a PLoS article. Previously, I had viewed commenting on the actual article site as a very formal procedure that required attaining the highest level of understanding of the article before submitting a comment. Essentially, I was viewing commenting on an online article the same way I viewed submitting an official comment to an article published in Science or Nature (or other journals). Published comments in those journals are almost always refutations of the article that seemingly without fail lead to concomitantly published rebuttals by the original article authors. Thus, the culture of commenting on articles is fraught with nastiness and putting one's scientific reputation on the line. This could be the reason that so far "official" online commenting on peer-reviewed articles has been very limited, whereas "unofficial" or off-site commenting has been more common. By "unofficial," I am loosely referring to comments made anywhere that is at least one link removed from the actual published article site. For example, an external blog, friendfeed discussion, or notes left on article managing services such as citeulike.
It occurred to me while laughing and crying my way through the recent friendfeed discussions (OK, fine, here's a link to perpetuate the madness) that this culture may be relatively easy to change. (Aside from any questions of whether it's necessary to change.) In my opinion, PLoS has already made one innovation that vastly increases the odds of a user making a public "comment." They have separated the article ratings into three categories: Insight, Reliability, and Style. From my personal experience, that opens the door almost all the way in terms of inviting some kind of reader feedback. Rating an article on "Style" does not carry much professional risk from my viewpoint. Rating on "Insight" requires understanding of the possible impact of the article, and is thus much more weighty than the "Style" rating. However, I personally feel I can rate an article on "Insight" without assessing the quality or reliability of the methods and data. I recently did this with a PLoS ONE article I saw on single-cell sequencing of uncultured organisms. To rate an article on "Reliability," I feel requires the kind of in-depth understanding that would be required for me to send a formal letter into the editor of Science or Nature that could be published. Thus, the barrier for me to rate on "Reliability" is quite high. Especially since if I'm going to put in enough effort to feel completely justified in rating, it's likely to be less than a 5-star rating. (I guess I'm feeling like I spend more time reading articles that I disbelieve than those I do believe?)
Another reason that placing online comments does not have to be as formal and negative as with traditional published comments is that the comments are published without a delay waiting for the original authors to compose a response. This then reduces the expectation that the publishing authors must respond and therefore takes the formality down a bunch of notches in my opinion. Also, in terms of PLoS the whole mission of the journal is to make research more broadly and rapidly available--and thus I think there is an expectation that the comments should also come from a broader base of readers.
So, that is what inspired me to take the time to read a PLoS Biology article and compose my first online comment tonight. I was also inspired by the belief that we're still very early in the process of dictating the culture of online discussions of peer-reviewed research--and thus a concerted effort can make impact in what ends up happening. This inspiration was combined with the coincidence that my wife sent me an article from BabyCenter today that caught my interest because it was discussing the recent PLoS Biology article. Finally, the thing that finally tipped the balance and convinced me to take the leap and make my first PLoS comment was a healthy dose of "WTF" So I stopped worrying and took the leap. :)
It's a pattern for me that I take on too much at the beginnings of semesters and then have to cast things aside as I get overwhelmed. Before this semester I took a big leap into communicating with scientists on the internet, via blogging and discussions with a bunch of new friends on friendfeed. As the semester engulfed me, I ended up casting aside blogging, but actually was able to maintain a lot of dialogue on friendfeed (e.g. in the Science 2.0 and The Life Scientists room). So, even though I was disappointed to not keep up the blogging, I can look back and see that overall I made a huge amount of progress in terms of scientific communication and meeting (virtually) many great people around the globe. I'm very happy with that, and I'm even happier that a couple of my graduate students came along with me. They have made their own connections with other scientists and made substantial progress in open science and open scientific communication.
I've been excited for the last week or two to ramp up the blogs again. In particular, I'm excited about a couple things. One is to try out Research Blogging. This was suggested to me by Michael Nielsen in a friendfeed thread in which I learned a lot, but which I started by spouting off way too ignorantly. My apologies to Richard once again! As I understand it, the service will allow me to write up blog reviews of specific research papers and then label my posts as suitable for listing in Research Blogging. For me, it will be a step up from what I started doing this semester, which is trying to make a few notes on every paper that I add to citeulike. You can see my citeulike RSS feed, with my comments added, on this Yahoo pipe. It will be a lot more work to write what I think is a worthy blog report about a paper, but I'm excited about testing the waters. The way citeulike is set up, I feel like my comments there are pretty much wasted as far as benefit to others goes. In the future, I'm expecting my group to communicate more via citeulike (or another service) as a form of "journal watch." But as it stands now, I'm pretty sure nobody reads the comments I add to my citeulike library.
The other thing that should be exciting is to write a guest blog for Lisa Green at NextBio. We've talked about this a bit, and I think it may happen in the next few weeks. What I will blog about that is worthy of a "guest blog," I don't know...but it should be a fun experience!
Finally, I needed some inspiration to come in here and start dusting off my blogs. I had been a bit depressed at their dormancy, which was a postive feedback loop preventing me from blogging. A blog warm-up idea came to me earlier tonight as I was staring at the ceiling fan. I recalled something I'd noticed maybe 6-10 years ago in graduate school, which made me recall something else I'd noticed at the same time. They're two "illusion" kind of things that I think are fun, and which I'm going to describe here without actually researching them scientifically. Hopefully someone who knows something will pipe in and tell us something about them!
1. Blurry motion seems slower with peripheral vision
I first noticed this illusion when I was trying to make large graphs in Origin back in graduate school. Whenever I made the mistaking of clicking on very large matrix plots, the graph would flash for like a minute before opening the graphing preferences window. I would look aside in frustration each time. And then I noticed that when I looked at the flashing graph (which was more like quick vertical scrolling of a dark patch), it seemed to scroll much slower in my peripheral vision. A few years later, I noticed the same thing when looking at a ceiling fan, an experiment much easier to reproduce.
Here is the experiment you can try
Find a ceiling fan that's not too far away, and spinning at about 2 hertz. When you look at it directly, if you're like me, the default image is to ignore the individual fan blades, and perceive a blur. You can change the image dramatically by following an individual blade with your eyes. For me, that motion seems "slower" than the blurry motion, but it's not the illusion I'm talking about here. The illusion that I see is when you quickly switch from looking at the fan with your central vision and instead use your peripheral vision. When doing that, the motion seems to slow down substantially. For me, it is substantial and repeatable.
I couldn't resist checking into this a bit on wikipedia, and I found something called "flicker fusion threshold" in this wikipedia article on peripheral vision. In the flicker fusion article, it is said, "so flicker can be sensed in peripheral vision at higher frequencies than in foveal vision." Given this, I wonder if the effect I am seeing has to do with some part of the visual system normalizing a given flicker relative to the maximum possible perceived flicker? The fan produces a constant rate of flicker...but it is a larger percentage of the fastest possible flicker when looked at with foveal vision?
2. I think you can hear individual splashes in the roar of a waterfall.
(Photo by Ant J on Flickr.)
This is an experiment I can't replicate easily now that I live in Albuquerque. We do have waterfalls in the mountains, but it's nothing like when I lived in Ithaca, NY during graduate school. Almost every day, I would cross the bridge over the waterfall at the end of Beebe Lake. This was on my way between Clark Hall (the physics building) and A-Lot, the parking lot the bus dropped off at. I would often stop and stare at the falling water. I noticed one day that if I followed with my eyes a particular part of the broken stream from the lake to the point at which it hit the rocks, I could audibly hear it "splash" within the "blurry" roar of the waterfall.
Here is the experiment you can try
If you have access to a waterfall, this experiment isn't too difficult to try. As I mentioned above in item 1, you can track the blades of a ceiling fan with your eyes, and this is the same thing you need to do with the waterfall. Track a "patch" of water all the way from the point at which it starts falling to when it hits the rocks or water below. Keep doing this repeatedly in a cycle, and you should "hear" the individual splashes--or at least I do. It's also fascinating to just look at the water as it breaks into pieces on the way down.
I just attempted 30 seconds of lazy google research for this phenomenon and was not successful at uncovering a wikipedia article to give insight into this effect. I am 50% sure it's an auditory illusion, and the other 50% of me thinks, "why not...maybe the sound isn't as 'blurry' as it seems?" It would be possible to check this with an objective audio/visual recording system.
3. The Blue Field Entoptic Effect -- Mystery Solved!
Also known as Scheerer's phenomenon. As opposed to the above two illusions, this one I now know what it is. I first noticed it on airplanes when flying in a really bright sky. In Albuquerque, we have bright blue skies frequently, and I can see the effect. According to wikipedia, most people can see what I see in these conditions: counteless point-like bright white things that travel in squiggly paths in the field of vision. It turns out that these are white blood cells flowing through the capillaries that cover the non-foveal parts of the retina. On a blue background (e.g. the sky), those capillaries produce very dark lines all across the field of vision--due to red blood cells absorbing blue light very well. Somewhere in the visual processing system, these dark lines are "edited" out, so we don't perceive them. However, when a white blood cell travels through, it is mostly transparent, and the increased light is perceived as a tiny white thing in the field of view (which it is, I guess). One of the most fascinating things to me is that it allows you to actually visualize your own blood cells flowing. According to the article, some doctors have tried to leverage this as a diagnostic technique.
How to try out the experiment:
This one is easy. Wait for a nice sunny day. Pick a big blue patch of the sky and stare at it for a couple minutes. Keep your attention focused on looking for bright dots appearing and traveling in squiggly paths. You won't be able to follow individual ones, but by trying to use your peripheral vision, you can see hundreds or thousands of them. They are quite different than "floaters." They are smaller (point-like), quicker, and more fleeting.
4. The McCollough Effect -- An amazing optical illusion
I'm including this one because I realized that I ended up having a common theme of "can you believe your eyes?" The answer is "no!" apparently. So, I'm including this final, amazing illusion that is well worth trying out.
How to try out the experiment:
If you have 10 minutes, you should go try out this optical illusion: The McCollough Effect. Spend the 5 minutes they recommend and then test it out for yourself. You can read a description of it on wikipedia. I found this illusion mind boggling, because for me it persisted for DAYS after I'd spent the five minutes training whatever part of my visual system that is being trained. Just an amazing demonstration of an ability to unwillingly and semi-permanently "program" part of your brain (or visual system at least) just by staring at some images for a few minutes.
11:22 am update
Steve says: I just read Gideon Burton's excellent post about "Intellectual Apartheid." One of his recommended steps for administrators is "Update promotion and tenure policies to favor open access publications and to accommodate evolving scholarly genres (such as data sets, software, and scholarly tools that build the cyberinfrastructure)."
Earlier this week, my department chair sent our department a link to an article in The Chronicle of Higher Education about MIT's open-access policy announcement. (I believe there is the standard irony that the article from the Chronicle is limited-access, but you may be able to find freely available stories on Google news.)
Without being an expert on open-access or doing much background research, I decided to send the following email to my department. I'll let you know what happens (if anything)!
Email to Physics & Astronomy faculty:
This got me to thinking. Our department could adopt a simple & public policy, such as: "Regarding new faculty hires and promotion & tenure decisions, we highly value an open access publication record. We place a value on open access publishing comparable to the value we place on publishing in top-tier scholarly journals which may have limited access." I don't know whether we could agree on such a statement, but if we could, I think it would place a positive light on our department, similar to how the MIT and Harvard statements below do for those universities.
As a tenure-track faculty in our department, I do feel that open-access publishing will be viewed positively by the voting faculty. It would be good to know that more formally, but I'm not worried. A much more worrisome thing for me is how open-access publishing will affect my Ph.D. students.
Will they lose out in job searches or will they stand out? Our own department's stand on this issue won't help our own students. But maybe by taking a public stand, we can set an example that other departments can follow.
I think it'd be worth spending a bit of time discussing at an upcoming faculty meeting.
--Steve
I was telling my grad students this story last week, and they liked mocking me so much as "assistant to a robot" that I thought I should post the story on here so more people can mock me. My first job in a research lab was the summer before starting my undergraduate career at the University of Michigan as a physics major--1992. I was really lucky get a summer job in one of Francis Collins' labs at UM. Yes, I am name dropping. The name I just dropped was that of Francis Collins, who was leader of the NHGRI from 1994-ish to 2008. Prior to that he was at the University of Michigan, with primary roles of hiring me as a work-study student and also leading teams that found the genes for cystic fibrosis, Huntington's disease, neurofibromatosis, and other diseases.
I have been lucky so often in my life, and in particular in my career "planning." I'll tell you some other day how lucky I got in obtaining my current job at UNM. This is how I obtained my first job in a research lab: I was friends with Dr. Collins' daughter, and I liked science. I knew he had a research lab because he had visited our classroom in Junior High to tell us about cystic fibrosis and genetics. So, I asked my friend if I could work in her Dad's lab. A few days later, she told me, "he says yes," or something along those lines. I was 17 years old at the time. But when writing this story, it seems like I was younger, as I recognize this strategy as the same one I used for obtaining a rollerskating "skate" with a girl in the 6th grade. I think the song was "Manic Monday."
I actually worked in a lab led by Chandra Sekharappa, who I think now has this lab. He was such a great guy and I am eternally grateful to him, Dr. Collins, and the other people in that lab who welcomed the unusual physics undergraduate to their lab. As I am writing this blog entry, a flood of memories are coming back to me. I learned so many things from working in this lab, and now, 17 years later, they are still coming back to me and helping me in my research (which coincidentally, or probably not coincidentally is tending towards genomics applications). In this lab is where I learned to pipette. I learned what PCR was. I unfolded paper towels for Northern blots. I "stuffed tips" (FYI: I could use each hand independently on two different boxes). I helped with "rows and columns." I washed dishes. Wow, did I wash dishes. I became obsessed with: -80 freezers; dry ice; vacuum-bake ovens; centrifuges; liquinox; reverse-osmosis water; latex gloves; latex gloves filled with water and frozen in the -80C freezer; and latex gloves in the vacuum-bake oven.
I cannot even come close to expressing how important this experience was to my career. Being immersed in this environment was so valuable -- whether I knew it at the time or not. The lab was focused on cloning the gene for early-onset familial breast cancer. (I believe another lab ultimately beat them by identifying BRCA1, but I'm not sure.) There was such a palpable excitement about the race to find this gene and I loved watching it. I distinctly remember that Dr. Collins welcomed me into group meetings, where the postdocs or grad students (I'm not sure what they were) would pass around these developed images of gels with the faintest of bands that proved something about their PCR reaction. I distinctly remember that they'd let the ignorant physics undergraduate stare at the film and then tolerate it when I said, "I think you're crazy, there's no band there." Somehow they kept inviting me, and they kept trying to explain to me "gene jumping" or "chimerisms" or "FISH" or other topics. The collaborative atmosphere in Chandra and Francis's lab is something I'm striving to replicate in our lab at UNM.
OK, now onto the good part. Of course, being the undergraduate in the lab made me a target for the grunt work. More than that, I wasn't even a biologist! So, it happened that the lab (or someone on the floor) had gotten their hands on a robotic system that could essentially print microarrays on filter paper. Or perhaps the predecessor to microrrays. The "robot" could print media from sixteen 96-welled plates onto a single filter paper. Then, these 4x4 arrays could be used for some kind of hybridization assays. This was a big deal, and the robot cost something in the 100's of thousands of dollars. Basically, you'd put a stack of 16 microtiter plates in the holder next to the robot. You'd set up the filter paper, and then the robot would proceed to: grab a plate; take lid off plate; put plate down; stick pins in plate; stick pins on filter paper; clean pins; put lid on plate; put plate away; repeat with new plate.
The problem was, the robot was controlled by some kind of SGI machine that nobody knew how to program. It cost a whole bunch of money to have the tech rep come out and program the thing. Everything about the robotic system worked well. Except, after taking the lid off the plate, it accelerated too fast, and media would splash from one well to another. This was terrible. I know what you're thinking: ask the physics undergrad to reprogram the robot! This is what I was thinking too when the grad students (or postdocs) explained to me the problem. I'm pretty sure I could have figured this out, no matter how obscure and proprietary the programming language. But, this was not my fortune. Instead, what they had figured out was that my $5.50 / hour salary was a perfect solution. I could perform the first part of the robotic sequence (grab plate; take off lid) and then at the appropriate time, hand the plate to the robot. So, this is when I took on my esteemed position as "assistant to the robot." I don't know how many days this lasted ... probably not too many, I think maybe for a few hundred plates or so. I do remember how utterly boring it was. I actually tried to read a book in 20 second increments while I tag-teamed with the robot.
Perhaps during my time as Assistant to the Robot, I impressed people enough to get my first promotion in the lab: to actual robot. (I previously mentioned my prowess at stuffing tips and unfolding paper towels, which probably factored into this promotion.) This job took most of a summer (1993 maybe?) and actually I'm pretty proud of it. My task was to copy the Washington University YAC (yeast artificial chromosome) library. I think it was about 200 96-welled plates and it took me most of a summer to make two copies. I became the most efficient plate-pourer of all time (in my own mind), and discovered that you can actually pour them so thin that even yeast can't grow. I wonder if these YAC libraries are still around nowadays?
Well, that's the anti-climactic ending to my story. I don't have a coherent point, and I know this goes against all of the how-to-be-a-good-blogger advice. My points are: (1) I collaborated with a robot in the past because it was cheaper than fixing the robot and (2) I had an awesome undergraduate research experience that has profoundly impacted my career. In regards to (2), there are so many lessons I can learn to help me in my current position as a research mentor. The main thing I have been thinking is that undergraduate research can be valuable for the lab, and incredibly valuable for the undergraduate. I feel like we're not even coming close to achieving what we could at UNM in regards to undergraduate research, and I would like to change this over the next couple years. I routinely meet Junior-level physics majors who are interested in research, but haven't yet been in a lab. We are next door to Sandia National Labs, and only 2 hours away from Los Alamos National Lab...both of which have amazing resources and opportunities for undergraduate scientists. And of course, we have plenty of our own labs at UNM. One of my goals over the next few years is to help our students find research jobs earlier in their careers...perhaps even before they start at UNM. Whether their jobs can be as prestigious as my own assistant to robot jobs, I don't know, but I can definitely strive for that!
SJK Note 4/2/09: I found a picture in my garage of the completed robot project. That's me admiring my 400? or so microtiter plates, all nicely stacked and labeled.
I live on a cul-de-sac where we are lucky enough to know and enjoy hanging out with many of our neighbors. Many have kids who play with our kids. It's like when I was a kid, and I thought those days had passed, but they haven't. (As an aside, I love hyphen-ating words, but it bothers me that cul-de-sac is hyphen-ated.)
Many of my neighbors really enjoy hearing about the science we're doing in the lab, and I really enjoy talking about it with them. This actually led to a very fun event we did during Winter Break where I brought in some neighbors to our Junior Physics lab course so they could get hands-on experience with some very cool physics. You can check out our OpenWetWare page (unfinished) for the event (sorry the facebook page seems to be private). A brief summary is that I only had to invest a few hours of time, and I think the attendees really enjoyed it. I know I did.
Recently I had an idea for science outreach that I'd like your opinion on. The idea is that I (or a student) will explain our research to one of our biggest neighbor fans. Then, we'll record an interview with him describing our science, what we do, it's importance, etc., from his point of view. Or we could do it with a couple neighbors talking. But the main point is that the non-scientists will be explaining the science to the (mostly) non-scientist audience on youtube.
There are a few reasons I think this may be useful and fun. First, I always find it informative and fun to hear people "re-describe" our research to someone else after I've described it (unless it's printed in a magazine). Second, I have an inkling that it would be effective for communicating to non-scientists. Third, the people I have in mind for this project are very good at picking out the essence of what I'm telling them, and distilling it down to the exciting parts in layman's terms.
So, do you think this is a good idea? Maybe it's been tried before many times, and if so, please send me the links. If we do give this a whirl, there is one thing I'd like to figure out how to do:
- Record video with two cameras (for example, one on me, one on him)
- Splice and edit the video to make a good video for posting to youtube
There was recently a very interesting thread regarding open notebook science in the Science 2.0 friendfeed room. This was in response to Michael Nielson announcing that Tobias Osborne had begun doing open notebook quantum information theory. I think this is fantastic, and my kudos go to Tobias (whom I don't know). The friendfeed debate had to do with whether Tobias's work can be called open notebook science, which has a specific definition.
The debate got me thinking again about something that's been bothering me recently. I've been having a hard time getting my thoughts straight, and that's still true. I'll quote myself and then try to clarify:
A really good motto for a scientist who wants to be open could be this: "Be as open as I personally want to be." This is very different than "be as open as possible." What I am specifically thinking is that young scientists (i.e., not yet beaten-down) seem to usually have very natural tendencies towards open science. But the overall level of natural talent for openness may vary enough that "open notebook science" may just not be the best method of openness for some people. But everyone can strive to "be as open as they want to be", and resist pressure to be closed coming from outside (fear of scooping; lack of technical means; resistance from colleagues). In contrast to these external pressures, I think it may be legitimate for someone to want to be open, but also maintain some privacy so they can get a personal reward of doing something all by themselves, for example. Perhaps posting all of their electronic notes 6 months or a year down the line.
"Be as open as I want to be." I don't know if that has value for anyone else, but it a very powerful mission statement for me right now. It's powerful, because I really believe in it, but I am not achieving it. I'll talk about that later in the post. But, first I want to talk about it in a more positive light.
What kind of openness should be required?
I am starting to decide that I'm not going to try to force my lab members to do specific kinds of open science. I am thinking instead that my goal will be to remove as many barriers as possible so that my lab members can achieve the level of openness they desire. I believe that adults have unchangeable natural talents, and I think that scientists will be cutout for different kinds of openness. For example, Anthony in our lab has recently started doing open notebook science, true to its definition. I am really excited about this. He is a natural for ONS. I don't think that he has any problem writing anything in public. In fact, I think his notebook being open is a motivator for him to make it even better than he would a private notebook. This is the way he's wired, and it's not surprising if you know him. In contrast, I think some people would find that their creativity and drive are seriously hampered by doing ONS. For example, me as a graduate student. I don't know whether doing ONS would have worked or not. I actually kept what I think is a very good electronic lab notebook. But it was private, and I don't know whether I would have taken as many notes (and dropped as many F-bombs) if I knew it was public. I also don't know if I would have reacted well to someone posting a suggestion to me when I was immersed in trying to figure out something by myself. I do know that I would have been fine posting my notebook in public with some time delay. In fact, if anyone posts a comment to this blog asking me to post my grad school notebook in public, I'll go ahead and do that...f-bombs and all.
So, while I don't think I'll require ONS for all lab members, I may have other requirements, such as delayed notebook publishing. What I am worried about is hampering creativity and productivity of young scientists by striving for inappropriately selected open science goals. I do want my students (and postdocs in the future) to strive for open science, but I want them to do it in the way that best leverages their talents.
I am failing at my own principles
"Be as open as I want to be." I and our lab have made some great strides in the past few months towards this principle. For me, I think the transformation was fueled by a strong belief in the power and even morality of open science. But it did take a heavy dose of "what the fuck" to spark the flurry of steps I took this past winter break. (I think that may be my first f-bomb while blogging; I feel alive.) I'm happy and excited about what we're doing. But I'm also not achieving openness as much as I'd like. And I'm confused. Two themes dominate my struggles with openness:
- The students in my labs and their scientific careers
- My collaborators, their careers, and my gratitude for their assistance and mentoring
Being scooped would be emotionally devastating. This is true. And it would have an impact on my lab and my students. This is what my students and I have been discussing the past couple years, and I think we've developed a collective (perhaps unspoken) understanding that we'll be OK even if that does happen. I think I can protect and rescue my students from that scenario. The collaborator issue is so much more complicated.
The collaborator issue is what is bothering me quite a bit now, and I really don't have any answer. Most of the scientists I know personally are "traditional." The ones I am trying to collaborate with are outstanding and highly respected by everyone, including me. The ones I am thinking about right now have put in a huge amount of effort helping me throughout various stages of my career. These traditional scientists, of course, are not Scientists 2.0, but they are fantastic scientists. I suspect, and in some cases directly know, that they would not approve of my science openness. So, I don't know how to deal with this external pressure towards closed science. The "what the fuck" strategy seems so disrespectful to people who've put energy into my career. But the "try to convince" them strategy is futile. "Showing them the way" will work...but at the risk of looking like "what the fuck" along the way and angering them. If we do get scooped, my students and I will be OK. But our mentors may never forgive us?
OK, I'm going to stop now...those are the challenges that are really bothering me this weekend.
I think it's been about a month since I started these blogs and joined friendfeed. It's been a whirlwind, really. I've e-met dozens of scientists around the globe in that short time, most of them much farther along than I and my lab are in terms of open science. The community of scientists out "here" is incredibly welcoming and helpful, and I want to send a thank you out to whomever of you read this post.
It's also been a time of huge change in terms of our lab's open science activities. We have started a lot of new open activities, and I thought I would make a list of them here. I'll only list those things that are new since mid-December, and I think it's quite a lot.
Blogging
Of course, I started blogging. We also started a blog that I and our lab members to contribute to. So far, only Anthony and I have contributed to it, but that will evolve over the year, I think. So far for me, blogging is a treat and I've been able to rationalize doing it based on potential synergies with the activities I'm supposed to be doing :)
Posting grants in public
We started posting our grants on Scribd. I chose this site from advice from Jean-Claude Bradley and Cameron Neylon. So far, I've liked the site as a place for sharing grants and other documents and it seems to work well. As an example, here is the grant we submitted last week. Posting grants has been really helpful so far and I expect it to continue to be helpful. We've received helpful comments from a couple people, and also made some science connections because of it. For example, Cameron and I realized we have a lot of science interests in common!
Paper preprint
A big step we took is we drafted our first paper out of our lab and we posted it on Nature Precedings. Larry Herskowitz is the lead author on this paper. We posted it a week ago, and we immediately received very helpful comments, questions, and suggestions from Richard Yeh. We're using OpenWetWare to talk about the paper with Richard and any others who want to join. My opinion right now is that OpenWetWare is a better place for these kinds of detailed lists of questions and suggestions, because we'll easily be able to break it into different topics, create sub-pages, and post supporting data, figures, etc. (In contrast, we found that trying to write the paper on a wiki just did not work for us at all.)
Open research projects
We have also taken some big steps towards "open notebook science" in the past month. We've been using a private wiki for about two years now, hosted by OpenWetWare. As I understand it, providing us with a private wiki was part of an experiment to see if it could draw in more users and lead them towards open science. You can't scientifically extrapolate from our experience, but then again, you don't have to approach it scientifically...so, my opinion is that providing the private wiki worked out beautifully for OWW's mission. I think they should continue to provide private wikis, including for select new users on a trial basis. It's quite possible (impossible to prove, though) that none of the open science activities I'm describing in this post would have been started had not Jason Kelly offered me the private wiki two years ago. Thank you Jason & all the OWW founders! I'd also like to thank Bill Flanagan who has helped me tremendously in many areas of the public and private wikis.
Having prepared via our "warmup time" with the private wiki, many of the students in my lab have begun to take open notebook steps in the past few weeks. You can find links to these on our open-research projects section. Anthony Salvagno has started doing real open-notebook science, keeping his daily notes on OWW, using the Lab Notebook system that Ricardo and others developed. Anthony is about to start learning molecular biology in our collaborator's lab, with guidance from Kelly Trujillo. The lab is not accustomed to e-notebooks, so it's going to be really tough for Anthony to not be driven to use a paper notebook. We'll see how it goes, I'm hoping he can show them the way!
Caleb Morse is embarking on some MediaWiki projects and we're trying to do our communication via OWW. There are many interesting things he might pursue this semester, many of them improvements to OWW and / or MediaWiki that can make the conduction of open research much easier. For example, he's currently working on modifying an extension to MW that uses cookies to prevent data loss when the browser crashes or closes while editing a page. This would be a huge plus for OWW.
Finally, Andy Maloney joined our lab in October and has learned to use the wiki very quickly. He recently took his first leap into the public wiki by posting his incredible instructions on how to build a laser diode control system from OEM parts. I'm also pushing him to post some of his earlier research accomplishments on OWW, including a custom microscope he built for imaging ultrasonic fields via the sonoluminescence. His Google SketchUp drawings and fly-by animations of the thing are amazing and I want you all to see them!
Open teaching
I've also started posting teaching material on Scribd. I'm trying to be careful about copyrighted material, so I'm not sure whether I can keep that up. One of the things I try to do after lecturing is to "debrief" to help with next year's lecture. So, combining blogging with Scribd is a good way to do that.
Back Pat
Looking back over that list of new things we started doing only recently has made me feel great about our lab. Obviously that rate of science "opening" can't continue. But I really do think we'll be able to keep up most of the things we've started, and I'm excited about that. On our private wiki, use a template that Anthony wrote for giving yourself a pat on the back. You just add {{BP}} to a page to use the template, and then you get an electronic pat on the back and feel good about yourself. Or at least some of use do. So, I'm going to put {{BP}} on this article and it's for me and all the students in our lab for these accomplishments. It's also a {{BP}} for all of the scientists I've been talking to recently and who have helped us take all these steps. They've provided very valuable advice and examples about how to do it, as well as encouragement and feedback for the steps we've taken. Thank you!
So, I just got back from a vacation--no internet access for a week! Ugh--I think some people find getting away from it all rejuvenating, but that is not me at all. In fact, this would be a complete non-talent for me. "Non-talent" is terminology from a book that I re-read while on vacation: "First Break All the Rules..." by Buckingham and Coffman. I first read this book several years ago, when I was immersed in the misery of being mismanaged. The concepts in this book are not complicated and to me even seem obvious (now that I've thought about them), but it still seems to be true that most managers ignore these concepts. Re-reading the book last week was even more illuminating, now that I've had a couple years of being a manager myself and can reflect on my own strengths and weaknesses as a lab manager and plan small changes that may have a big effect on outcomes for our students and the science we're doing.
One of my talents is the ability to read these kinds of management and leadership books without getting too hung up on the fact that they're not perfect science. Though, I do like this one especially because it is founded in a whole bunch of research (the authors are out of Gallup Consulting) and objective analysis. Via hundreds of thousands of interviews with employees and managers across all types of industries they tried to determine common qualities of managers whose groups far outperform the others. Thus, they tried to find out what great managers do differently than good and bad managers. The main points they found out ring very true for me, and really, THE main point is that great managers recognize the following things:
- By the time people are grownups, their brains have been "wired" in unique ways because of their genetics and their experiences growing up. These genetics and experiences produce a set of talents and "non-talents" for any individual. The authors refer to this as the unique "filter" each individual uses for their everyday experiences. The key point is that these talents are not teachable to grownups and great managers recognize this. Skills and knowledge contrast with talents, in that they are teachable. Learning skills and knowledge is easy for someone with underlying talent in that area. Learning skills and knowledge without the underlying talent is a constant uphill battle.
- In order to succeed and be happy in a particular job, a person needs certain talents. Great managers figure out what those talents are, and try to assess those talents when hiring people. Contrast this with the system most of us are familiar with, where people are assessed based on resumes and interviews which focus on skills and knowledge. Determining what talents a job requires is not easy. It's even more difficult for a manager to assess someone's talents. And possibly, for many people, the most difficult thing is for an individual to assess their own personal talents--I know it is very difficult for me.
- A great manager spends time helping his people discover their own talents and helps them make career decisions based on those talents.
I think while reading this book in graduate school was the first time I'd consciously considered talents existing for things besides athletics, music, acting. I think I easily accepted, for example, that professional musicians had innate "hard-wired" abilities that enabled them to enjoy the hard work it took them to achieve that kind of excellence. I knew I didn't have those talents and didn't entertain any notion that I could just "work really hard" to become a professional musician or athlete. But I don't think I ever considered the vast array of other ways people could be talented, or non-talented, and I think I was probably a subscriber to the popular notion that I could succeed at any kind of job I landed just by forcing myself to work hard. And if I was failing it was my own fault for not working hard or smartly.
While considering that last paragraph, I think it's not quite correct. Back then, I probably did recognize the existence of many talents, but I had not sensibly defined them. For example, I may have thought I had a "talent for science," since from 1st grade through graduate school I had received good grades and succeeded in science "things." Therefore, I would have deduced that I have a talent for any kind of career related to science: graduate student, professor, R&D, science writer, elementary school science teacher, science policy advisor, etc. In fact, I think I entertained the notion of all of those careers at some point. I probably made the reasonable step of considering whether I'd like those careers, but I did not even come close to considering that it was my own talents and non-talents that would determine whether those careers would be thrilling or miserable.
Ever since reading that book, I've been wondering about my own talents. Ironically, I'm untalented at discovering my own talents. I suppose some people are very talented in this. When I preach to my students about this topic, I'm often asked, "What are your talents?" I know that I have many talents, and some I know specifically. For example, I know that I absolutely love computer programming. I can work on data analysis applications for 16 hours straight days at a time and love it. This is a talent for me, and considering that I was spending 10 hours a day in 3rd grade playing around with BASIC on my Commodore 64 this is not a surprising talent. But it's one I don't get to use very much any more, due to my career choice. I also know that I have a lot of non-talents. I think it's just as important to discover these, and for me these are easier to find. I'm still not quite sure what it's called, but I have at least one non-talent that would be required for easy writing of scientific papers and grant applications. In contrast, I find these blogs fun and fairly easy to spew out--I enjoy this kind of writing, and I probably have some kind of talent that is being used by blogging. But there is something about the precision or brevity or efficiency or whatever about formal papers and in particular grant writing that give me serious writer's block. I have been writing grants for two years now and it is always unpleasant and very difficult. I feel like I produce good documents, but it is very far from easy.
That last point is the key: it's not easy. (And I don't enjoy most parts of it.) This is a great way of discovering talents. In the book, they cite a manager (anonymously, unfortunately) who developed the "Sunday Night Blues Test." He asked his employees to stop and think on a Sunday night whether they were happy the weekend was over, or whether they were a little depressed. (Assuming a five day work week.) The employees then were to consider what specific things they had planned to do the next day. Their level of happiness / unhappiness about their activities the next day would be a way of understanding what talents or non-talents they possessed. I like this test, and it's helped me quite a bit in assessing myself.
I've used a variation of the test in the courses I've taught, in the hopes that my students will learn something about themselves far earlier than I ever did. On the last day of class in the four semesters I've taught, I've presented them this last un-graded homework assignment. You can view it on this openwetware page. I ask them to reflect back on the semester that's ended and to ask themselves which courses they're most sad are ending and which they are elated to be done with. I ask them to think about specific assignments that were fun or others that were dreaded. I don't have any kind of evidence, but I feel like there's enough variety of things students are asked to do that they may be able to discover talents and non-talents this way. A few of my students "turn in" this assignment via email or WebCT, and I always find it fascinating and pleasurable to read what they have to say. Usually these are students that I've come to know a bit, so I can give them a little feedback on it too, which I enjoy. (This probably indicates a talent I have for getting true pleasure out of students' successes.)
I realize this blog is getting long. I think I did say above that brevity is a non-talent of mine. I'm considering breaking this into two posts, but instead, I think I'm going to leave it as one post glued together by this added paragraph.
So, as I mentioned above, I re-read this book a couple weeks ago, and I must have marked up every other page and wrote down several dozen ideas it gave me for how to better teach, manage our lab, and be a better person. One of those ideas which I've followed through on is to work on identifying talents of the students in our lab. I have a few reasons for wanting to do this. The most important reason is that I want to maximize the success of every student that comes through our lab. I really believe that the more they can understand about themselves and their talents, the happier and more successful they will be in their next career step. The next reason is that I can manage the lab much more effectively if I know what talents and non-talents my students have. I'm not sure I have the talent to do this, but I am sure that it can't hurt for me to know more.
Believe it or not, I actually had a "talents" meeting with all three of my graduate students this week...between 2 and 3 hours with each person. I even went so far as to use the interviewing questions from the book. This was really cheesy, but my students trust me enough to have followed through honestly with the process. The questions are designed to reveal talents. I left the book in my office, so I can't quote any of them directly now, but some of the questions I found most revealing were:
- What keeps you working here? (in the lab)
- What is the best kind of praise you have ever received? What made it so good?
- What is a productive partnership or mentorship you've had? Why did it work so well?
- What are your current goals and what is your timeline for achieving them?
- How often do you want to meet with me to discuss your progress?
All the questions are good, but those are coming to mind now as having elicited responses that pointed towards talents or non-talents.
I don't want to get into any specific results here, because my students and I didn't really discuss yet whether this process would be open or not. Actually, what I'm hoping is that through this continuing dialog, it will become a habit of our lab to point out to each other obvious talents and even non-talents. I think we have a lot of respect and trust in each other, so it's likely we can achieve this kind of productive openness. In any case, without being too specific, I can tell you that I was really surprised at how much I learned from these meetings. Even considering that I already expected them to be productive meetings. Again, I think I am lucky to have very good and trusting students, so our dialog was very open. In addition to the questions from the book, I also asked each student to talk about their most productive time(s) in the lab so far. (Another variation on the Sunday Night Blues Test.) I found this incredibly useful.
One of the most humorous, surprising, and potentially useful result was what I learned about the students' and my own talent for competitiveness. If someone has this talent, they are driven to compete and win against other people. A different kind of talent is a need for achievement. This is different, because it is not relative to other people, but an internal measuring stick and a desire to constantly improve. It turns out I and one of my students have a strong competitiveness quality. This didn't surprise me too much. What did surprise me was that the other students did not have this quality. One common flaw of managers is to follow the golden rule of treating others the way you'd like to be treated. I have this flaw too. Up until this week, I think I'd pretty much assumed that everyone was competitive. But what I discovered is that's completely not true. I had also down-played my own competitiveness, and I now realize it's an important part of me and my motivations. So, what can I do with this information? I'm not sure, but given how surprising some of it was, I don't see how it can make me a worse manager. Just a simple example is that if you try to motivate an achiever and a competitor by having them compete against each other it's not going to work well. I don't think I've tried do that, but as a manager I'm always doing something , whether or not I'm trying to.
I'm going to try to wrap up this wandering post now. If you have a talent for reading management or self-help books, I strongly recommend you read the book I've linked above, "First Break All the Rules." If you don't have that talent, I do recommend trying out different ways of discovering your own talents. During the few weeks I've been on FriendFeed, I've already seen a few people making or considering career moves. I think talents are the number one thing that will determine whether these moves produce success and happiness. A perfect example is the ineffective way in which university faculty are chosen. Successful graduate students and postdocs are evaluated for professorships based upon their achievements, skills, and knowledge as researchers in the lab. The job, however, is not at all similar. I am now a manager, teacher, grant-writer, leader, and I don't know what else...but I'm not doing research in the lab very often if at all. In light of the selection process (and the utter lack of training), it's not surprising that there is so much struggle seen in this career path. Luckily, I think I do have enough of the talents required for my job, and I can ultimately succeed.
One requirement for the dossier is the "expanded statement of scholarly professional achievements and future goals." I deduced from the outset that most people weren't going to look at my dossier, and those that did would look at this section (as opposed to the interminable appendices). So, I knew the smart thing was to spend most of my time on this statement. I didn't do the smart thing, however, so I ran out of time to revise my statement as much as I would have liked. This is a common occurrence with me, and is part of my lame time management "strategies." I don't think my statement was too bad, though, and I think if people read it they'll get a good impression of my real goals over the next couple years as a professor here. I figured I would post it here on my blog, so I'm posting it below. The only changes I'm going to make are a few minor changes and insertion of some hyperlinks here and there (we submit the dossier on paper still!!!) if I think they're helpful. I really welcome any comments, questions, and critcisms!
Here is the statement (converted from Word format):
Science goals: Our lab's research area is in experimental single-molecule biophysics. To us, that means that we are primarily physicists by training, and we are applying our physics skills (building instruments, data analysis, automation, nanoscale physics) to problems in molecular cell biology. In order to maximize our impact, we seek collaborations with outstanding biologists with whom we can identify key open problems and design new experiments. Currently, our research focus is on the molecular aspects of DNA damage repair and gene transcription—two important research areas for understanding and developing treatments for all types of cancer. For example, we are using biophysical tools such as optical tweezers (an instrument that can apply and measure tiny forces on single biomolecules) to develop methods for mapping DNA by unzipping single DNA molecules extracted from living cells.
People goals: Young scientists will be the key to our lab’s success and to the long-term impact of our research. We seek to recruit diverse people with strong talents for experimental research and a passion for biophysics. Mentoring in ethical science and professional development of young scientists in the lab is a key goal and will be partially achieved by open communication and involvement of lab members in all aspects of lab operations, including funding, teaching, and outreach.
Funding goals: Our research requires people, instruments, and supplies, and thus substantial ongoing funding is essential. My goal is to obtain multi-year renewable funding that is sufficient to fund a lab of several graduate and undergraduate students and all necessary supplies. An NIH R01 grant ($200K / year direct for 5 years) is a major goal and is an ideal funding level. An NSF CAREER award ($100K / year direct for 5 years) would be a significant achievement and sufficient in combination with student fellowships. Numerous other sources of funding for our type of research are available (particularly shorter-term “idea” grants), both from public and private sources and we will pursue all of these, including after obtaining a big NSF or NIH grant. Graduate students and postdocs will also be encouraged to apply for fellowships from NSF, NIH, and other sources.
Impact Goals: First, we believe that open sharing of our plans, methods, data, results, software, etc. is the best way to speed the progress of science, the understanding of our results, and adoption of our methods. Thus, “open science” is a major goal, and one aspect of this is the traditional goal of publishing in high-impact peer-reviewed scientific journals and presenting regularly at national meetings. Second, we strive to leverage our exciting research in our teaching and service goals (below). Third, we will maximize impact through training and mentoring of students and postdocs who will make further innovations in their future careers beyond our laboratory.
Research accomplishments:
- Interdisciplinary collaboration. We have established several valuable collaborations.
- Our collaboration with the Mary Ann Osley lab (UNM Dept. Molecular Genetics and Microbiology) has resulted in generation of key biological materials (such as DNA constructs), some preliminary data, letters of support for grant applications, student fellowships, and two conference presentations.
- Collaboration with the Steve Brueck lab (UNM CHTM) has resulted in a NanoLetters publication, letters of support and preliminary data for grant applications, and student fellowships.
- Collaboration with Evan Evans (Physics, U. British Columbia; Biomedical Engineering Boston U.; Adjunct Chemical Engineering UNM) has resulted in Evans bringing two state-of-the-art single-molecule manipulation systems to the CHTM, joint recruitment of a postdoctoral researcher to UNM (funded by Evans NIH grant), and initiation of a joint research project.
- Collaboration with Karen Adelman lab (NIH National Institute of Environmental Health Sciences) has led to letters of support for grant applications and agreements to share biological materials for upcoming single-molecule research.
- We are planning collaboration with Susan Atlas lab (UNM Physics and Cancer Center) and Chris Lorenz Lab (Mechanical Engineering, King’s College London) and have submitted proposals with each lab as co-PIs as well as obtained letters of support for other grants.
- Instrumentation. Graduate and undergraduate students have played major roles in all aspects of lab start-up—providing valuable fundamental knowledge at the expense of slowing down construction. We have currently built prototype low-power optical tweezers (OT) and stretched single-DNA molecules using DNA constructs we have produced at UNM. Construction and calibration of a high-power OT system will be completed in Spring 2009. Also, partnership with Evans lab and student knowledge of OT has resulted in access to Evans’ state-of-the-art and fully calibrated OT system that he has recently (November 2008) completed transferring to a lab we share at the CHTM.
- Lab IT infrastructure. We have in place very successful hardware and software that will serve all of our needs in data storage and backup, global sharing of data and methods, and collaboration. One key to this is a 2 terabyte RAID-5 server with VPN firewall running Windows Server 2003, Exchange Server 2003, and Internet Information Services (IIS) that was setup by a talented UNM ECE undergraduate (Caleb Morse). Another key component is a MediaWiki-based lab wiki (courtesy of OpenWetWare) that we use for all lab notebooks, lab communication, and some communication with collaborators and grant writing.
- Major results and preliminary data. Our most major research achievement has been proof-of-principle for “shotgun DNA mapping,” led by Ph.D. student Larry Herskowitz. Larry is currently writing a paper for submission to Biophysical Journal, will present a poster at the 2009 Biophysical Society meeting, and we have submitted a patent disclosure to the STC. Our collaboration with the Brueck lab has resulted in a 2008 NanoLetters publication. We have also developed two fully-functioning software applications for stochastic simulation of eukaryotic gene transcription that we hope to publish in 2009. All of these results will provide key preliminary data to strengthen grant applications in 2009 and beyond.
- Student recruitment. We currently have three physics Ph.D. candidates in the lab, all funded by fellowships--two have NSF IGERTs (two years of funding) and one has a CHTM / Emcore fellowship (8 months of funding). Two of these students have been in the lab from their second semester (spring 2007), while one student (R. Maloney) passed all of his exams and carried out significant research in the Thomas lab before transferring to our lab in late 2008. A “post-bacc” student, Diego Ramallo Pardo, performed research in our lab for over a year as part of the UNM PREP program and he is now at Stanford biophysics graduate school. An undergraduate physics major (Linh Le) is currently carrying out honors thesis research in our lab. We hosted an NNIN REU student summer of 2008. Finally, an ECE undergraduate and a biochemistry undergraduate student have carried out research for credit in our lab since early 2007.
- Funding. We obtained an American Cancer Society (ACS) starter grant for $22,500—this is an institutional research grant led by Janet Oliver in UNM Pathology. This is an important foothold in cancer research funding and is seeding preliminary results for NIH, NSF, DoD and other applications. Numerous national peer-reviewed grant applications have been submitted—none have been funded so far, but we have received much positive feedback.
- I have also participated in a number of grant writing workshops, including a year-long monthly NIH grant writing workshop (led by Laurie Hudson, UNM College of Pharmacy), a one-day NSF grant workshop (led by UNM Chem. Eng.), and an NIH NIGMS mock review panel at the Biophysical Society Annual Meeting 2008.
- Open Science. We have implemented mechanisms for carrying out open science: OpenWetWare lab site with numerous protocols published; Optical tweezers control software project on Sourceforge; Lab server with Windows Server applications for sharing data over internet. I was also mentioned in an article about Open Science published by the Howard Hughes Medical Institute (HHMI). (12/27/08 Note: I don't like the way I was quoted, though!).
Upcoming Research Goals:
- Funding
- Continued attempts to obtain major multi-year funding. (Maybe get lucky with a pending grant!) In 2009, planning NIH R01 to National Human Genome Research Institute, American Cancer Society (national) Research Scholar Grant, resubmission of NSF CAREER, resubmission of Human Frontier Science Program (HFSP), DoD Breast Cancer Research Program Idea, and other opportunities that develop.
- Improved networking with program managers in Washington—face to face meetings when possible.
- Mentoring graduate students in obtaining NIH NRSA (fellowship) and other funding.
- Science
- In 2009, we hope to achieve major progress and publications in three areas: shotgun DNA mapping; unzipping analysis of chromatin and RNA Polymerase II transcription complexes; nanochannels analysis of DNA and chromatin. These projects will be led by the three graduate students as major focuses of their dissertations and will be in collaboration with the Osley, Brueck, Adelman, and Evans labs.
- Also in 2009, we hope to initiate research and obtain preliminary data to initiate the collaborations with Atlas and Lorenz labs.
- People
- I do not plan on soon expanding beyond the three graduate students plus the shared postdoc with Evans. I do plan on maintaining the level of undergraduate involvement in research by recruiting REU students, undergraduates from outside physics department, and future honors thesis candidates in physics.
Teaching
Teaching Goals:
My primary mission in any course is to help students achieve goals that will benefit them in their future careers. These goals will differ depending on the course, level, and target population. Some goals will be specific learning outcomes (e.g. physics concepts) whereas others will be a broader foundation of the students’ careers (e.g. attitudes towards science; general research skills). I also strive to enhance my courses by leveraging exciting results from my research group and implementing educational innovations. While setting these goals is important, so is measuring progress—thus I intend on implementing assessment (pre- and post-testing) that is backed by education research. Finally, in any course I teach, I am a role model, leader, and motivator for the students in their university careers. Thus, I seek to maximize my accessibility to the students by facilitating many modes of interaction, particularly by leveraging modern communication, including email and messaging on WebCT and wikis.
Teaching Accomplishments:
- Two courses developed (Physics 102 “Intro Physics” and Physics 307L “Junior Lab”) with above average ICES scores.
- 27 PowerPoint lectures, hundreds of quiz and exam questions, and dozens of clicker questions and homework puzzles developed for Physics 102. Implementation of Just in Time Teaching (JiTT), peer instruction, and interactive lecture demos. Use of WebCT Vista for quizzes, homework, and communication with students. (12/27/08 Note: please let me know if you would like these materials, I am happy to share!)
- Wiki-based TA / instructor collaboration system developed for Physics 102. Mentored TA and two graduate RAs through process of developing and presenting one lecture.
- Innovative “open science” wiki system implemented for Physics 307L—completely electronic and public lab notebooks, lab summaries, formal reports, and instructor feedback.
- Attended American Association of Physics Teachers (AAPT) “New Faculty Workshop” in November 2008. Learned about a variety of research-proven physics instructions methods and where to find further information and teaching resources.
Upcoming Teaching Goals:
- Implementation of research-proven assessment in all courses (pre- and post-testing).
- Refinement of teaching strategies, based on published physics education research that I learned about at AAPT workshop.
- Presentation at UNM teaching conference and possible publication of innovative teaching strategies I’ve implemented so far. (12/27/08 Note: I am starting to do this with my new teaching blog.)
- Teaching a third course in P&A department (probably calculus-based intro physics).
Service
Service Goals:
University: My goal for university service is to help guide and improve research and education in the department, college, and university through active participation in a few committees. Local community: My goals for service in Albuquerque and New Mexico are (a) to improve science education, (b) recruit minorities to the university sciences, and (c) improve the understanding and enjoyment of science by non-scientists. Nation: My goal is to make an impact on biophysics at the national and international level by committee service in the Biophysical Society, journal referee and grant reviewing service, “open science” leadership, and recruitment and mentoring of young scientists, including minorities.
Service Accomplishments:
- Participation in numerous committees in department, CHTM, and university-wide.
- Minor committee member for two Ph.D. students outside my lab.
- Several outreach activities with students and teachers in NM at middle and high school levels.
- OpenWetWare leadership—especially electronic lab notebooks.
Upcoming Service Goals:
- Participation in another P&A committee within the next couple years– graduate recruitment desirable.
- Service on Biophysical Society national committee ( I have volunteered and expect to be appointed in 2009).
- Continued leadership in Open Science via involvement with OpenWetWare.
- Expanded journal referee and grant review service.
- Expanded local community outreach. I want to continue my lab’s involvement in local science fairs and I would like to develop partnerships with local science teachers as part of likely NSF CAREER award resubmission in 2009. I would also like to expand UNM’s role in local Habitat for Humanity projects, based on what I learned via participation in Sandia National Labs’ successful Habitat for Humanity program—but this will likely have to wait a few years.
Today I set up three blogs that I am going to start using soon: Steve Koch Science (this blog), Steve Koch Research, and Steve Koch Teaching. I'm planning to use this science blog for posts about open science (aka Science 2.0), lab management, or other science professional issues which don't fall in the teaching or research areas. The research blog will be about our research, grant writing, etc. That leaves teaching for the teaching blog. I'm still not sure whether it will make sense for me to have three separate blogs, but I think it may...I'm modeling this after Rosie Redfield's research and teaching blogs. In addition to her blogs, I'm also inspired by some other people such as Maureen Hoatlin's lab twitter and friendfeed, Cameron Neylon's "Science in the open" blog, The Science Commons blog,
Posts
Last week, I submitted my third and final attempt at the NSF CAREER proposal. As with my prior two attempts, I pledged to publish the proposal openly, and I'll stick to that pledge. Despite my sleep deprivation, if I had been satisfied and proud of the proposal, I would have taken the time to post the proposal right away last week. The truth is, though, that I am demoralized and embarrassed by the proposal--all due to my own shortcomings. Well, I painted myself into a corner by promising to publish the proposal openly, so I can't hide it permanently. But as a compromise with myself, I am allowing myself to publish only the Specific Aims section now, which I am reasonably happy with. A copy can be found on slideshare: CAREER: Open-science studies of effects of water isotope and osmotic stress on biomolecular interactions. I will publish the disastrous remainder of the proposal once I have the stomach to do so in the next few weeks (before it goes out for review).
I remain happy with the Specific Aims, which many successful grant writers argue is the most important section of the proposal. What I like most is that I decided to elevate "open science" to be one of the three specific aims. I also love the science I am proposing and would love to have my students focus on this research plan over the next five years.
So why a failure? Well there are many failures, the worst and most embarrassing is that I completely ran out of time and did not submit even close to a decent final product. I guess those of you who can't avert your eyes from the worst train wreck will see this when I post the full version in a few weeks--and I'm not kidding. As I mentioned above, this is all my fault. I made a huge mistake and attempted to completely rewrite the proposal instead of tweaking the 2009 version. The 2009 proposal was declined. The reviewers were very thoughtful and liked the research plan and loved the "broader impacts" of the open science, as I described in another post. They just did not believe I could carry out the research as we did not have enough preliminary data. I think I would have had more than a 50% chance of getting it funded this time, if we'd generated a lot of preliminary data supporting the proposal over the past two years. It would have been relatively easy to revise the proposal and assuage the reviewers' concerns. However, we failed at generating much of this preliminary data. We did get some data, but not enough, and have been stymied in large part due to lack of funding. My lab was very lucky to receive funding for an unrelated project from DTRA, and thus we spent most of our resources (time and money) on that project (kinesin) as opposed to generating preliminary data for the DNA unzipping work.
I could have added in a lot of new data (and "spin") and I think the tweaked CAREER proposal would have had a shot at getting funded. I also think it would have been reasonable for NSF to fund it, because given the amount of funding ($150K / year for 5 years), we would have received the necessary resources to pursue the research. So why didn't I go this route? I wrestled with the decision for many weeks with no path obvious to me. I ultimately went with my gut and decided to scrap most of the proposed DNA unzipping research and to instead rewrite the proposal to focus on the solvent effects of water on kinesin and protein-DNA interactions. There were many pros and cons I weighed, consciously and sub-consciously, but I'd say the prominent reasons for rewriting were the following: (a) I'm worn-down by years of pursuing the DNA unzipping project without the proper financial or human resources, (b) I'm fascinated by the question of whether deuterium is essential for some cellular processes (c) I don't have the ability or desire to manage a lab that is pursuing two large and separate research projects and (d) our funded project--studying the molecular motor kinesin--is going very well, is exciting, and, frankly, seems much more doable since we've had two years of sufficient funding for it. While the kinesin grant saved my lab and allowed the graduate students to remain in our lab, it did have a side effect of diverting most of our resources from the project we had been pursuing to map native chromatin by DNA unzipping.
In retrospect, I think I made a good decision, but I waited much too long to decide, a huge mistake. I spent as much time as I could on the rewriting, but just flat-out failed. Big time. So badly I still don't have the stomach to talk about it. Because of the deadline and the point I am in my career (tenure decision this academic year), delaying submission was not an option. So, I submitted a version that is very poor in many areas. I feel bad about wasting the time of reviewers, including those from 2009 who obviously spent a lot of time coaching me on how to improve the proposal. I hope, maybe, that some of my ideas despite being poorly written will still be enjoyable to the reviewers. What I feel worst about is that I really like the research proposed in the Specific Aims. I think it's the research path I should pursue and the students would succeed and make a big impact. And I totally squandered the opportunity to have it funded by the NSF CAREER program. So, even a week later, I remain embarrassed, disappointed, disgusted, etc.
I suppose there are bright sides. As we all know, research funding rates are very low anyway--so even a perfectly-written proposal would have been lucky to have been funded. And, if I don't piss off too many reviewers, I can still pursue funding via the many other funding avenues that I need to pursue anyway. And if I don't get the funding, I think the ideas are still worth pursuing. So, by openly publishing the entire mess, maybe another group of researchers will be encouraged to pursue the open questions with their own resources.
SJK August 18, 2011: As promised, I have posted the full Project Description. Here is a link on SlideShare: http://www.slideshare.net/skoch3/2011-nsf-careersteve-koch-full-project-description
But that's not what I want to talk about tonight. Tonight, I want to ask the question: Have life forms adapted a use for deuterium? Or is it merely tolerated? To talk about this, I will go back to really fun 1933 letter to JACS by Gilbert N. Lewis1. I found this paper because of our work with D2O in the lab and my quick realization that my initial assumptions about D2O were way off. I had assumed that D2O was pretty much like regular water, just a bit denser. I completely missed the point that D (deuterium: one proton, one neutron) is chemically very different from H (hydrogen or protium, one proton, zero neutrons). This is because the reduced mass of an H-X bond is substantially different from a D-X bond, and thus the binding energy is substantially different. (X refers to some other atom such as oxygen or carbon.) It turns out that the chemistry of D is so much different from H that relatively pure D2O is toxic to eukaryotic lifeforms! D2O also has many other amazing effects on life forms and biomolecules. For example, it stabilizes microtubules2, which is a major reason it is toxic3. It also increases the thermostability of proteins4 or even whole fruit flies5. Last fall, I summarized some of the things I learned about D2O in a group meeting.
So, while I was naive in 2009 (and likely continuing 2010->), Gilbert Lewis was amazingly prescient in 1933. In his letter to JACS, he says, "Sir: Even before I had succeeded in concentrating the isotope of hydrogen, I predicted that H2H2O would not support life and would be lethal to higher organisms." Don't you wish research letters today began so strikingly??? What a breath of fresh air(rogance)! The letter goes on to describe a beautifully simple experiment that he was able to carry out to demonstrate the toxicity of D2O to tobacco seeds. He used tobacco seeds because they are tiny and he only had a small amount of D2O (that he purified himself). He showed that 6 tobacco seeds in regular water sprouted nicely over the course of two weeks. Whereas 6 tobacco seeds in reasonably pure D2O did not sprout at all. Tobacco seeds in 50/50 D2O / H2O (which would be 50% H1H2O) sprouted, but slowly. At the end of the letter, Lewis says, "I have long desired to determine the proportions of isotopes in living matter, in order to see whether the extraordinary selective power of living organisms, which is exemplified by their behavior toward optical isomers, might lead to a segregation of isotopes in some of the substances which are necessary to growth. The marked biochemical differences between the two isotopes of hydrogen lends a further incentive to this search." It's not exactly clear, but I have to guess that Lewis was wondering whether living organisms would use D and H differently, and whether he could detect this via deviations from the ratio of D to H in (standard mean) ocean water.
To me, this is a fascinating question. Do cells use D for specialized purposes? If not, do they use pumps, etc. to increase the concentration of H inside cells and reduce the toxic effects of D? When I mention this to most scientists, it seems to set off their "crackpot" sensors, which is understandable. I mentioned this to Steven Benner at a DTRA program review a few weeks ago and his crackpot sensor initially was triggered. He said, "Deuterium is only 1 hundredth of a percent [of the total hydrogens in regular water]." I said, "But that's 17 millimolar!" He said, "OK, well you changed the units on me..." But then he changed his tune a bit and I think he considered it plausible.
0.03% does sound trivial. But the way I look at it, biology has somehow evolved to make use of different divalent cations in much lower concentration, such as magnesium, zinc, calcium, etc. And it can distinguish between potassium (K+) and sodium (Na+). How much more different are K+ and Na+ from each other, compared to the difference between D and H? I actually don't know, but my intuition would say it's in the same ballpark. I find it remarkable that regular water has 17 millimolar of deuterium "contamination" in it, and up until 2009 it never occured to me that it could matter! As an example, if you're studying a proton pump at the single-molecule level, 1 out of six thousand events may be artificially slowed because D is in there instead of H. This could make a difference, especially if studying events like pausing. (There is a recent paper by Yuan and Berg that studies isotope effects in the bacterial rotary motor that I have not yet read carefully6.)
So, at some level it seems important to remember that there's a lot of deuterium in regular "pure" water. But more interesting to me is whether life has adapted uses for this deuterium. I think if Lewis had had easy access to deuterium-depleted water, he would have investigated this right away. But as far as I know, deuterium-depleted water didn't become readily available until many decades later (I could be wrong on this). I think Lewis' tobacco seed experiments are the perfect place to start studying this effect. My hypothesis is: tobacco seeds in deuterium-depleted water (<1 part per million D; Aldrich product no. 195294) will sprout more slowly than in "regular" water with approximately 150 parts per million D. To test this, we only need:
- Tobacco seeds (cheap, right?)
- Deuterium-depleted water $25
- 500 microliter microfuge tubes, a camera (maybe microscope?), and some time
I'm obviously not the first person to think of this. I'm sure Lewis thought of it, but didn't have the resources. D-depleted water is cheap nowadays, probably because of its use in NMR. A google search for "deuterium-depleted water" is ruined by a huge amount of links to products about the use of D-depleted water for curing all kinds of cancer. This is unfortunate. Digging around, I was able to find a couple peer-reviewed papers investigating the effects of deuterium depletion on life. The first I found is by Somlyai et all in FEBS 19937. They claim to prove that "naturally-occurring deuterium is essential for normal cell growth." This paper has been cited 10 times, and of those 10, I think only two investigate deuterium-depletion effects. Those two are by the same research group. Their results would be striking, but it is not convincing for at least two reasons. First, their level of depletion was not substantial: 150 ppm to 30-40 ppm (compared to <1 ppm which we can achieve now). Secondly, they investigate the effects on human cell lines. As far as I know, human cell lines are finicky...much, much more finicky than tobacco seeds. I think it was a mistake to jump right into cell lines.
The results of Somlyai et al. may be true, and if so would be exciting. Not, in my opinion, as an immediate cure for cancer, but rather as a fascinating new area of cell biology to study. I think a quick extension of Lewis' beautiful tobacco seed experiments is a great first step. If we don't see an effect? Try again! Maybe try mustard seed too. Steven Benner, indicated the next step (paraphrasing from fuzzy memory): grow yeast or E. coli in D-depleted water. Check for which genes are mutated. Those genes are candidates for encoding proteins that utilize deuterium for the benefit of the cell. Or proteins that sequester D, I suppose.
So, what do you think? Should we try this experiment? I think so, and I'll write up a proposed protocol in my OpenWetWare notebook soon (I hope).
PS: In addition to the short letter by Lewis I talked about above, I highly recommend reading a longer letter to Science in 19348. In his first paragraph he says, "Several months ago the experiments were interrupted, and since there may be no immediate opportunity of resuming them it seems best to publish the somewhat sporadic results so far obtained." Don't you wish you could publish your own sporadic results in Science? It's a very interesting paper where he describes further tobacco seed experiments as well as microorganisms, flatworms, and mice.
References (Send me a note if you'd like the PDF for the ref. 1)
1. Gilbert N. Lewis (1933). THE BIOCHEMISTRY OF WATER CONTAINING HYDROGEN ISOTOPE Journal of the American Chemical Society, 55 (8), 3503-3504 DOI: 10.1021/ja01335a509
2. Panda, D., Chakrabarti, G., Hudson, J., Pigg, K., Miller, H. P., Wilson, L., et al. (2000). Suppression of microtubule dynamic instability and treadmilling by deuterium oxide. Biochemistry, 39(17), 5075-81. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10819973.
3. I think there is a study from 1935 that looks at cells in D2O and sees larger spindle apparatus in mitotic cells, but I can't find the reference now.
4. Sen, A., Balamurugan, V., Rajak, K. K., Chakravarti, S., Bhanuprakash, V., Singh, R. K., et al. (2009). Role of heavy water in biological sciences with an emphasis on thermostabilization of vaccines. Expert review of vaccines, 8(11), 1587-602. doi: 10.1586/erv.09.105.
5.Pittendrigh, C. S., & Cosbey, E. S. (1974). On the Very Rapid Enhancement by D2O of the Temperature-Tolerance of Adult Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 71(2), 540-543. Retrieved from http://www.pnas.org/content/71/2/540.abstract.
6. Yuan, J., & Berg, H. C. (2010). Thermal and solvent-isotope effects on the flagellar rotary motor near zero load. Biophysical journal, 98(10), 2121-6. Biophysical Society. doi: 10.1016/j.bpj.2010.01.061.
7. Somlyai, G., Jancsó, G., Jákli, G., Vass, K., Barna, B., Lakics, V., et al. (1993). Naturally occurring deuterium is essential for the normal growth rate of cells. FEBS letters, 317(1-2), 1-4. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8428617.
8. Lewis, G. N. (1934). THE BIOLOGY OF HEAVY WATER. Science (New York, N.Y.), 79(2042), 151-153. doi: 10.1126/science.79.2042.151.
FriendFeed thread:
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The NIH has a specific definition for "new investigator", which is any investigator who has not been PI on any PHS-supported project other than a "small" one, such as a K-award or R-21 grant. New investigators get many benefits in review of R01 grants, including:
- Instructions to the study section to go easy on the new investigators (again, see the link from the Center for Scientific Review).
- Center-specific practices to increase paylines and grant duration for new investigators. For example, the NCI in the past extended the payline from the 11th percentile to the 16th percentile. The NHGRI was not as specific, but they also increased the payline and also strive to support new investigators for 5 years.
New PIs and Early Stage Investigators (ESIs) are invited to apply for Recovery Act Challenge Grants in Health and Science Research. Because the awards made under this program are substantial competing NIH research grants, recipients will not be considered New PIs or ESIs when they apply for NIH research grants in the future.
Thus, if I were to win a two-year RC1, I would no longer be considered a "new investigator" for future R01 applications. This is a serious issue to consider. Two years of funding would be great, but five years of funding would be much better. Furthermore, this rule, combined with other language in the RFA makes me wonder whether new investigators will be frowned upon overall in the review process?
Does anyone else have any thoughts on this issue? I am heavily leaning towards not applying for RC1. But I also know that I'm biased by the fact that I just submitted a couple grant applications (to other agencies) and the thought of doing another one in the next three weeks is really not appealing!
SJK Note added 8:06 PM: Another negative is that there are no resubmissions of RC1s, since it is a one-time program.
SJK Note 4/2/09: Friendfeed comments.
In this post, I want to elaborate on why I think our ideas are important but unique, and therefore not in direct competition with most of the leading labs in the single-molecule manipulation world today. The table below illustrates why I think we can lead a new era of experiments in an under-tapped area of single-molecule analysis--"single-molecule genetics." I am using a 2x2 matrix to analyze the research space. This is a technique I learned during the end of my graduate career when I interviewed and almost landed a job with Boston Consulting Group (BCG, a company I highly respected). The top row represents ensemble assays where the properties of many molecules are averaged together. The bottom row represents the single-molecule analysis research world. The left column represents experiments where the system being studied has been reconstituted from purified components. The right column represents experiments where the system being studied was intact, with only a few specific genes having been mutated or knocked-down*.
The top left quadrant represents what people refer to as biochemistry research, whereas the top right quadrant would be genetics**. The vast majority of the important discoveries in biology in the past half century would be in the top row (ensemble assays). Single-molecule assays in the bottom row have been very valuable, but are only now becoming more widely available. In my opinion, the vast majority of single-molecule assays have been in in the bottom left quadrant, which I am calling "single-molecule biochemistry" for convenience. For example, the Steve Block lab has made a number of breakthroughs in this quadrant. The Block Lab is a good example, because the research and papers produced by the students and postdocs in this lab over the past couple decades are of the highest quality and have played a key role in defining the single-molecule field. One of their areas of study is RNA Polymerase, where they have applied forces to recombinant E. coli RNA Polymerase during elongation in all sorts of manners: opposing elongation, assisting elongation, pulling on the RNA transcript, etc. Another main area of the block lab is the molecular motor kinesin. They have used optical tweezers to make many important discoveries about the mechanochemistry of this amazing enzyme. From these two areas combined (which still account for only part of the Block Lab research), they have something like 10,000 Science, Nature, and Cell papers. And as far as I know, all of that research has been done using dozens of different recombinant RNA Polymerase and kinesin heavy chain (KHC) motor proteins. So, as far as my matrix goes, they have made a huge impact on the bottom left quadrant -- "single molecule biochemsitry."
As I've said, I think the bottom right quadrant has so far been under-utilized. I am calling this quadrant "single-molecule genetics," to highlight what I see as the untapped power of combining proven single-molecule analyses with existing genetics techniques. When I say "untapped," I don't mean to imply that there aren't existing studies in this quadrant. I only mean that most of the research (and money) from single-molecule manipulation groups I am familiar with has been going into the SM biochemistry quadrant. This includes groups such as those of Steve Block, Carlos Bustamante, Evan Evans, Mark Williams, Jeff Gelles, Vincent Croquette, David Bensimon, Steve Kowalczykowski, Julio Fernandez, Matthias Rief, Herman Gaub, Sanford Leuba, Rich Superfine, Michelle Wang, and many others. I believe the labs I just mentioned perform research primarily in the "single-molecule biochemistry" quadrant. There are many examples of outstanding single-molecule analyses in the bottom-right quadrant. One of my recent favorites is from Osheim, Sikes, and Beyer where they used electron microscopy (EM) visualization of chromatin fibers extracted from Drosophila to study Pol II termination at the single-molecule level. "DNA fiber analysis" is another great example of research in this quadrant. The biomembrane force probe that Evan Evans' lab uses also lends itself to research that I would put in this quadrant. For example, the work of Heinrich, Leung, and Evans, studied ligand-receptor interactions on living human neutrophils. Another important example is from Cui and Bustamante, who studied the mechanical properties of individual native chromatin fibers from chicken erythrocytes.
The Cui and Bustamante work is closest to the killer application we are pursuing. We are working to use single-molecule DNA unzipping to map the positions of nucleosomes and polymerases on specific native chromatin fibers. This will be different from the Cui and Bustamante work in a number of ways. First, we expect to be able to map the positions of nucleosomes and polymerases with close to basepair accuracy. Second, we will analyze positions on site-specific chromatin fibers. Thus, we will know which gene it is, where the promoters and terminators are, etc. You can read more about our ideas in a recent minigrant proposal which I posted on Scribd. (This was funded by the way!) Our single-molecule research will complement the ensemble studies currently used -- commonly Chromatin Immunoprecipitation (ChIP). Because we will analyze chromatin extracted from living yeast cells (and higher organisms in the future), we will be able to study chromatin remodeling as genes are turned on or off and in any mutant strains we'd like. This is the same genetics as is carried out in the ensemble assays (top right quadrant), and in fact, our collaborators (Mary Ann Osley lab) currently do much research in this quadrant. We think our single-molecule method will be particularly good for addressing many open questions related to chromatin remodeling during transcription. For example, the Osley lab recently showed that a yeast double mutant deficient in FACT and H2b-ubiquitylation has an interesting phenotype that seems to have some kind of misassembled chromatin. Deciphering this chromatin structure is difficult with ensemble assays, and single-molecule analysis can shed a lot of light on this question. For example, if the chromatin is being assembled with histone tetramers instead of octamers, that should be clearly visible in the single-molecule unzipping signals.
By pursuing research in the "single-molecule genetics" or bottom-right quadrant, I think we are poised for making important contributions that complement the other quadrants. I just illustrated how we can closely complement ensemble genetics experiments (ChIP). Further, we complement single-molecule biochemstry experiments in the bottom-left and ensemble biochemistry in the top-left. As far as Pol II experiments go I don't believe any single-molecule force v. velocity transcription assays have been carried out yet. The work of Shundrovsky, Hall, and others in the Wang lab in terms of unzipping reconstituted mononucleosomes is in the bottom-left quadrant, and it certainly complements our work, because we're relying on their results to know what to look for when unzipping native chromatin fibers. And we'll do some of our own work in this quadrant in terms of unzipping Pol II in vitro transcription complexes for a similar purpose. In contrast to nucleosomes, we expect the Pol II unzipping signature to look distinct for unzipping from upstream versus downstream. If so, this will allow us to determine the sense versus antisense orientation of polymerases on native chromatin fibers, giving us single-molecule insight into a very exciting area of eukaryotic transcription. (See, for example, a recent antisense transcription paper from Core, Waterfall, and Lis.)
OK, hopefully I succeeded at least a bit in describing how I think we can lead a new area of single-molecule research: single-molecule genetics. I'd be curious in hearing whether this "2x2 matrix" helps you at all in looking at the research space. I find it very useful -- but on the other hand, I also really enjoyed a business course I took, and I thought the interview process for BCG was really fun. So, I may be a little different. If you do find it useful, I have some other 2x2's I can talk about. For example, Single-molecule/Ensemble versus With Force / Without Force.
*Footnote on "in vivo" terminology.
I am using "in vivo" to designate that the biology occurred in the context of a native cell, even if the analysis of the molecules was carried out with an in vitro assay. This would be true, in Chromatin Immunoprecipitation studies of chromatin remodeling during transcription, for example. The transcription is carried out in the nucleus, then the cells are fixed with formaldehyde and analysis is carried out in vitro. I am consdering this an "in vivo" experiment, in contrast to studies where the transription has been carried out in vitro -- such as in the amazing reconstituted systems of the Reinberg lab and others.
Certainly the holy grail of "in vivo" would be to know the 3-D position and chemical nature of every molecule in real-time while the cell is still living. And many single-molecule researchers are making big strides towards this goal by visualizing and tracking individual molecules inside living cells. However, my focus here is more on the arena of single-molecule manipulation.
**Footnote on doo doo
I may not be getting the of biochemistry and genetics exactly correct, and I do know that there is some ongoing rivalry between these two fields. John Lis, one of my science heroes who taught a molecular biology course I took told us two quotations. I wish I could remember who to attribute these to:
Famous geneticist: "Genetics without biochemistry is doo-doo."
Extremely measured response from famous biochemist: "Biochemistry without genetics is an exercise in frustration."
SJK Note 1: I don't even know enough to know whether I've remembered these correctly. Possibly interchange genetics<-->biochemistry, etc. but you get the point: they are complementary research fields and there is a rivalry.
SJK Note 2: If you know a source for these quotes, please post a comment! I couldn't find it on Google. Also see some interesting related discussion on friendfeed.
We submitted our proposal for the internal American Cancer Society (ACS) Institutional Research Grant (IRG) yesterday. I've uploaded it to Scribd, in case you'd like to look. I am really happy with it! And I am really proud of the students in my lab for both their help on the proposal, and for their accomplishments in getting our new lab to point we are now. I feel like this year is going to be a whole lot of really great science and many accomplishments from them. I'd also really like to thank Mary Ann Osley and Kelly Trujillo, our collaborators at UNM, for help in writing this and developing the ideas. These ideas were developed with the help of Karen Adelman (NIH NIEHS) also. Thank you everyone!
I've uploaded a draft to Scribd of the specific aims section for a miniproposal I have due on Friday. The proposal is for $30K from an American Cancer Society (ACS) Institutional Research Grant (IRG) for one year of research. It is a renewal of the previous IRG we received which provided us with $22,500 for one year of research and for which we have been extremely grateful. While that kind of funding is much smaller than the NIH R01 funding we're striving for, it makes a big impact on our lab. I think any lab would appreciate that kind of funding, but it's particularly valuable to us in this start-up phase.
The proposal is due Friday (Jan. 23). To me, these specific aims seem very clear and I like the way they're written...so I think it's almost finished. But if you do happen to read it before Friday morning (or even after), I'd love to have your comments!
And, I should mention that this proposal is 7 pages in "NIH-style." That means it has sections of:
- Specific Aims
- Background and Siificance
- Preliminary Studies
- Research Plan
PS: Thank you to Anthony, Andy, and Larry for help in writing this, and for all the help from our collaborators, Mary Ann, Kelly, and Karen!
Today, our lab created a sort-of-complete draft of the first paper to come out of our lab. I wrote briefly about it on our kochlab research blog and also posted our draft on scribd. I don't want to re-blog everything here so I'll just say that we're really excited about the paper and if you happen to click on those links above, I (we) would love to hear your opinions.
I'm really proud of the lab members, and especially Larry, who did most of the programming and produced the results that are in this paper. He produced much of this during two amazingly productive months last year (say August/September-ish) when he was seemingly-happily working 7 days a week with many 10+ hour days. If you happened to read my previous blog about talents in the lab on my science blog, you may have just realized that that kind of dedication and productivity is indicative of some kind of underlying talent that Larry has, and I wholeheartedly agree. Larry and I recognized this during our recent "talents meeting," and we're wanting to analyze that time period as a way of more clearly seeing what these strong talents are.
In contrast to the research productivity, we've been wanting to draft this paper for several months now, and up until today it was painful for both of us. I definitely committed some management sins (I'm avoiding a euphemism we use in this situation), but I think he's forgiven me by now. Last week, we fully consciously realized that the writing process we'd been attempting was failing and so we decided to try something new. The process we had been trying was to collaborate on our private wiki by having Larry draft sections and I and others commenting on his work and making suggestions. There are probably many reasons this failed and I know many of them are due to non-talents I have with writing and management. The new process we tried today was to just block off a whole day in a conference room to work together towards a single outcome: to produce a document in Word that was a reasonably coherent draft of the paper that we could distribute to our friends and collaborators for advice. Anthony, Linh, Larry, and I did this today, and I think the experiment was highly successful. Certainly the draft we produced is very rough, and none of us will be surprised if >75% of it is changed as we revise and pound on it in the coming weeks. But I think we surpassed the outcome we were looking for and for sure we have achieved a very solid foothold towards our goal of actually publishing this paper in a refereed journal.
This process took us about 9 hours together, plus who knows how many hundreds of hours of discussions and prior writing attempts that we built upon. We were able to fight through several instances of writer's block today, particularly with the introduction, and I think the clear outcome we were pursuing was a huge help in pushing us through this. Many may question whether it's practical for me (or any of us) to schedule an entire day for writing a paper draft, and I hold the same question. I'm not sure whether we can or will need to do this in the future, but given the success, I think we'll try. Time like this is precious for all of us, but we received quite a valuable payout. I present my first lecture tomorrow (in about 13 hours) and I haven't made any preparation except for what I have from last year and a bunch of mostly subconscious scheming and worrying. I'll talk about this on my teaching blog, perhaps later tonight. I'm super-happy about the progress we made today, and very proud of my students ... and I also now have a really uneasy feeling in my stomach in anticipation of being unprepared for the onslaught of teaching and the grant deadlines. I should mention that the uneasiness is probably compounded by hunger, which would be the subject of another blog that I don't have.
I found out today that my NSF CAREER award proposal was declined. This was completely expected, and as I mentioned in my previous blog I have been looking forward to the constructive feedback that I know I need. Whether consciously or not, though, I now realize I was unrealistically hoping that I would receive mostly positive feedback and a few easy things to improve upon. Thus, my first read-through this afternoon of the detailed reviews was very surprising and wickedly demoralizing. Let me try to think of some other emotions: bewilderment, depression, frustration... OK that's enough. I think the most demoralizing aspect was that a response shared by many reviewers was that the proposal was poorly written and confusing. This must be true, given that the sentiment was shared, but as of now, I have no idea how to overhaul the proposal to correct for this, and I'm dreading having to figure that out.
At this point (5 hours later), I have carefully re-read all of the feedback, and my emotions are much more tempered, and a couple new ones have emerged: hope, gratitude. The gratitude is for the many scientists (5 reviewers, plus program manager, plus panel members) who clearly invested a huge amount of time in reading (and re-reading and deciphering my bad writing) my proposal and composing very detailed and thoughtful feedback. I truly feel badly and frustrated that I can't thank these reviewers personally, due to their anonymity. Really, the only thing I can do is to do my best to follow all of the advice they have given and correct all my mistakes with the resubmission this summer...and I plan on doing this.
Following advice of Jean-Claude Bradley, Cameron Neylon, and others, I have posted most of the potentially interesting and non-confidential parts of the proposal on Scribd. I am new to the site, but I think this is a link to the proposal. WARNING: reading the proposal has been deemed difficult and perhaps a waste of time by at least 5 respected scientists!
I am not going to post the reviewers comments, since I think they had the expectations that I would not share them. I will give a brief summary here.
Overall
- Two panels reviewed the proposal. Both panels ranked it low priority (approximately 50th percentile or worse). Ouch! One panel was the Molecular Genetics panel and the other was a special interdisciplinary panel between Mathematical and Physical Sciences and Molecular and Cellular Biosciences for interdisciplinary proposals such as this.
- I have feedback from 5 anonymous reviewers. I don't know how they fit into the two panels, or whether it's a 3rd source of feedback for the program manager. 4 reviewers understood the impact (in my opinion), whereas one reviewer seemed to hate my writing and didn't seem to understand because of that.
- All panels and individual reviewers had significant concerns about the proposal. There was no way this thing could have been funded without some kind of empty senate seat under my control.
- Involvement with OpenWetWare and open science was noticed and cited as a big positive for the broader impacts.
- Dearth of preliminary data / overly ambitious / seriously concerned about feasibility of any aspect of the proposal. This is very reasonable and somewhat expected. The students have been working hard on this project, we already have some significant preliminary data (related to "Shotgun DNA Mapping") and I expect a lot more before July of this year. I had sent in an update about the shotgun DNA mapping results in October, but based on reviewer feedback, I think that the program manager did not send this update to anyone. Another way I will address this issue is to re-organize the proposal (somehow) to make the feasibility more obvious.
- Poorly written and confusing. This sentiment was pretty much shared by all reviewers and even included in one panel summary. I have re-read the proposal many times since July and never really considered that it was so confusing. I was modeling the format after a couple funded CAREER awards that I had seen (in other fields, though). Well, clearly I need to improve this somehow and I don't have any good ideas. I feel bad that I caused so much trouble and wasted so much time of the thoughtful reviewers. One of the reviewers basically admitted to giving up, which I don't really blame him, given the comments from the others. I feel like I've been told that my baby is ugly and just can't see it. BTW, my kids are fantastically cute.
- Too many specific aims / third aim not well developed. I can see that this is true. One thing I stupidly didn't realize is that the reviewers basically expect NIH-style things such as "specific aims." I had actually suspected it would be viewed negatively if made it look too "NIH-ey." I will think a lot more about this, but right now what I'm thinking is that I should focus the science solely on Pol II transcription (ditch the DNA damage repair), and then reorganize the aims to be (1) shotgun DNA mapping (2) unzipping in vitro Pol II complexes and (3) mapping pol II and nucleosomes on native chromatin. This would be organized from most feasible to least feasible.
- Most of the reviewers specifically mentioned that involvement with OpenWetWare was a big positive for the broader impacts. This was really good to see, and perhaps the most notable thing to people who happen to read this blog.
- All reviewers agreed that the impact would be very high (if successful). Further, I think some were even intrigued / excited about the idea. Many of the reviewers understood and seemed to agree with a main point I was trying to sell: that the combination of single-molecule analysis with yeast genetics is a potentially powerful and unique tool for chromatin biology.
Overall, writing this blog entry has been therapeutic and also constructive. And if you do happen to skim any of the proposal, I welcome harsh criticism--I can stomach it!
SJK Note added Feb. 5, 2010: I did end up submitting again in 2009. The quick report is that I rewrote it in NIH style, and improved writing thruoghout. The reviewers liked the science, but lacked confidence in me as a PI, due to lack of preliminary results. Fair criticism that I think I can correct this year. Most importantly: the panel LOVED open science as broader impacts. Here're some links for my 2009 NSF CAREER proposal:
- FriendFeed thread discussing broader impacts feedback.
- Slide 6 of this presentation shows some of the positive reviews of open science from panel.
- Link to 2009 proposal on Scribd.
Any day now I should be hearing the results of my NSF CAREER award application. I've talked about this in one of my earlier blogs, where I pointed out that there is very little chance the grant will get funded--this is due to overall odds and the fact that it's my first submission. The latter point reduces the odds in two ways. First, I've been told by numerous sources that there is a bias (whether intended or not) towards 3rd-submission proposals (by rule, the final submission). The other reason it being my first submission reduces my chances is likely by far the most strong -- I have a lot to learn from the feedback I will receive! My resubmission in July 2009 will be much stronger due to this critical feedback as well as the very cool preliminary data my students have been acquiring (and which I hope to start telling you about in a couple weeks).
(As an aside, I feel compelled to insert this note: If you're my NSF program manager and you happen to have the time to to read this random blog, and you are in the middle of dialing my number to tell me that my grant was funded, and are now having second thoughts after having read that paragraph above, PLEASE KEEP DIALING!)
Aside from the fact that I lack some talents helpful for grant writing--and therefore find it painful--I did enjoy aspects of the NSF CAREER award writing. This is because the award is, by design, tailored towards research university professors and has required components on research, education, broader impacts, etc. This made me think deeply about my whole career (research, teaching, service, family) and even now when I go back and read my proposal (6 months later), I am excited about the integrated career plan. One particularly satisfying aspect was that I was able to include (admittedly vague) plans for open science in a very natural way and aligned with the mission of NSF.
So, I am really looking forward to the feedback about this proposal, and I think it will be the most helpful feedback I will have received so far. Up to this point, I have received some helpful critical feedback from the DoD Breast Cancer Research Program (BCRP) Idea Award (although that backfired on me...subject of another post), some internal awards, and that's about it. Many of the other programs--private foundations--provide little or no feedback (usually none) as a matter of policy, which makes the rejection somewhat less rewarding (ha ha). I am still considering the idea of posting my whole proposal (perhaps on Scribd per Cameron Neylon and Jean-Claude Bradley's suggestions). Until I figure that out, I figured I'd post the first page of my proposal, which gives an overview of my career plan 6 months ago. Please give me any negative or positive feedback you have!
The long-term mission of our laboratory is to enable important discoveries in molecular cell biology by innovating new biophysical methods and culturing interdisciplinary research and education partnerships. The specific research goals of this 5-year proposal are to develop new methods for single-molecule analysis of DNA and chromatin extracted from living yeast cells, and thus open a new research area that combines the powers of single-molecule and genetic approaches. Our long-term mission is also supported by our specific educational and broader impacts goals in this proposal, which will multiply the impact of our research goals. These include participation in Open Science, integration of research and university education, and community and local school outreach. Together, these research and education goals in this proposal will establish a successful career path for this PI as leader of an exciting biophysics research laboratory collaborating with leading chromatin and transcription biologists, successful university educator, and recruiter of underrepresented minorities to research careers.
Research Overview
DNA in eukaryotic cells exists as chromatin, which is repeating units of DNA wrapped around histone proteins. These DNA-histone units are called nucleosomes, and play a fundamental role in both positive and negative regulation of proteins that require access to the DNA code. Cells have a variety of enzymes that can modify the structure of the chromatin by moving, removing, or adding histones, or by modifying specific amino acid residues on the histones. This chromatin remodeling affects the ability of other proteins to access the DNA and has a profound impact on critical processes such as DNA repair and gene transcription by RNA polymerase. Understanding of these dynamic processes is currently hampered by the inability to characterize with high spatial and temporal resolution the changes to chromatin inside living cells. Therefore, we are developing biophysical tools with single-molecule sensitivity to address this need. One of the main goals we are pursuing is to develop a single-molecule method (see Fig. 1) for mapping proteins on chromatin that will far surpass the capabilities of the currently most powerful technique—chromatin Immunoprecipitation (ChIP). We are also pursuing other goals for analysis of genomic DNA and chromatin with optical and magnetic tweezers and nanostructured devices. The unifying themes of our research goals are single-molecule analysis and chromatin biology, and we are seeking to build a career foundation in a new arena of single-molecule biophysics applied to in vivo systems.
For about a year now, I have been using Dynamic Page Listing (DPL) for a variety of purposes on our private lab wiki (hosted by OpenWetWare). I find it very useful for keeping track of ideas, grant writing, and assigning goals and tasks, among other things. In this post, I want to talk about using DPL for goals and tasks, which I think is a system that could help out other people who want to carry out open science using MediaWiki with the DPL extension installed.
I met with an ECE undergraduate student today, Caleb Morse, and we decided to try out a small "open research" project on OpenWetWare. We are following advice in responses to my earlier blog (see the friendfeed discussion), and are going to try to do a small project completely openly. Thus, for this project we're starting from scratch and going to try to record everything on the wiki and other various public resources (to be determined: blogs, etc.). Our hub for this project will be this page on our lab wiki, and as we get it going, I'll describe it in a future post. We're going to use DPL Goals to help us in this project, and so today I set them up for Caleb on OWW and I also wrote an OWW help page and an example user to help others who may want to try it out.
What are DPL Goals?
What this system amounts to is really just a method for tagging and displaying tags with simple "AND / OR" logic. The only reason I have to write this article is because there isn't yet (as far as I know) a good way for tagging and good, simple tag filtering in MediaWiki. DPL is really good at doing this, but it's a powerful and complicated extension, so it's a little confusing to set up the system I'm describing here. The system basically works like this:
- Pages are created to describe goals or tasks. Categories are added to these pages to (a) mark them as a goal, (b) assign them to a specific person, and (c) optionally categorize them further, such as "high priority."
- Task List or Goal List pages are created to display any pages across the entire wiki database which have been marked as goals or tasks for a specific user. This listing page updates dynamically whenever another page on the wiki is added.
The following figure shows a screen shot of an example page for listing goals and task pages. Each of the links is to a separate page somewhere on the wiki (it doesn't matter where) that can have a lot of detail about a research goal, or could have no text at all, with the title simple being a task reminder.
There are four lists presented in the previous figure. The wiki code for this page has four blocks of DPL code to generate the lists automatically and dynamically...as tags (categories) are added or removed from pages around the wiki, the list will be updated (when the page is refreshed). Two of these blocks of DPL code are shown in the next figure.
You can see that the code isn't too complicated, but it's not completely straightforward either. I should note that this is just one particular way of displaying pages. DPL is quite powerful, both in it's extraction of pages (and bits of pages) and in the ability to format the results. What I am showing is a very simple usage with just page titles that tends to work well for me.
The DPL code necessary for generating the display page is a little bit complicated, but only needs to be generated once (and you can tweak the display later if you like). In contrast, the wiki code needed to make new pages show up in the list is very simple--This is why I think the method can be helpful to me and potentially others. I show in the next picture the basic use of MediaWiki categories, which is not too complicated.
The use of templates, which I won't show here, can make it even easier. The template method is actually what I use, and it's exceedingly easy to remember and quick to use. Furthermore, if OWW or your site decides to make tagging easier (check boxes, or tagging like on other sites), the method should get even easier. Along those same lines, what I'm describing is still a kludge and a much better method may already exist or may be introduced soon. I think it's easy enough to do and has been so helpful to me that I think it's worth implementing if you don't have a better option.
What next?
As I mentioned above DPL is very versatile, and what I'm describing is a very limited application that has been very helpful to me. I use the same basic paradigm for many purposes on our private and public wiki. Many of the pages on OpenWetWare tend to be long articles, in the style of wikipedia. On the other hand, scientific research tends to generate bits of information here and there--this makes it much more convenient for me to make small entries that have some tags (aka labels, categories) so I can aggregate them on some other page. I'd say I spend 80% of my private wiki time with this method. For example, when grant writing, I'll take notes without worrying where I list the page, and then I'll just add an "NIH R01" tag to the page so I can find it later. If you use MediaWiki and especialy OWW, I think you'll like this method. Here are two more links to DPL uses I have on OWW public wiki:
- An aggregation of ideas I have for possibly improving our Junior Lab course next year.
- Various pages with ideas for improvements to the wiki (I don't really use this very often, but it's a good example of what can be done easily).
Welcome to my research blog! If you've read any of my teaching or science blog, you may know that I made the highly questionable decision of having three separate blogs. So far, this decision is bothering me, and not a single post has fallen nicely into any of those areas. I'm still hoping this isn't a big deal or too annoying to any readers I may have.
This research blog has been the hardest one to start, because I am still wrestling with issues of open science. Being partially open is difficult (and this time consuming and distracting difficulty is a big argument in favor of being completely open). But I am still concerned about taking a full-on dive into open science. I truly feel that my main worries are the risks it presents my students and (and to a much lesser extent, my collaborators). This risk arises because the students' careers are tied strongly to the success of our lab. So, any risks to our publications, and particularly our funding directly impact the students (and of course my career). It's actually not a fear, but I think it's a consciously planned precaution. My instinct, actually is to just say "f it" and to immediately put everything into the open--my gut tells me that this would actually lead to much more and quicker research success. I think my students would mostly agree too. However, I think this may add risk to our lab's success. My students are already taking a big risk working with the new un-tenured, un-funded guy...so I'm hesitant to pile on extra risks. Thus is my justification for our open science baby steps.
Given that sort of thought process, I thought my first blog post here could be about our research lab principles (including thoughts on openness), as opposed to directly about the science we are pursuing. To do so, I posted on our public wiki an old (very old by web standards) early 2007 draft of a lab philosophy that I have had posted on our private wiki. I'm hoping it can evlove into a set of principles that more than just me try to improve on.
I always cringe when I re-read something I've written some time ago (so I guess I should group all of my blogs together into one called "Steve Koch Cringes"). This draft of our lab principles is no exception. But I'm resisting the urge to edit it now and I've just posted it as is. If nothing else, it's a good snapshot of what was going through my mind as a new, confused, but concerned professor. Now I am a rapidly aging, still confused, still concerned professor...whose having a lot of fun with all of the great students he has.
I feel like it's a waste or confusing to copy over the entire post to this blog entry. I also fee like it would be difficult to relink everything, so if you're interested, please do follow this link.
Posts
I'm in the process of reorganizing my site and as a result my frequency of posts have plummeted. Unfortunately this will continue until I'm ready to make an announcement. Stay tuned...
It's been quite awhile since I've posted on here and for that I apologize.
The International Balloon Fiesta is upon us here in ABQ. I'll have my official report for the Great New Mexican Adventure up soon, but I thought I would share all the pics I took from my first ever trip to the fiesta. Check them out at my new photo site photos.iheartanthony.com.
I've contacted the Susan G. Komen affiliate here in NM but let's get as many people together for this as possible. I want to donate in a big way and the only way I can is by donating the money that you provide by pledging for the tshirts. Let's fight the disease together!
The original design can be seen below:
My mom had her breast cancer race at Central Park in NYC and she brought some friends with her. One of them named Stacy is a breast cancer survivor. Click the jump for a couple pictures from their fun day (and to see my t-shirts in action)...
| From left: Robin, Stacy, my mom (Barbara) |
| ...smile for the camera! |
| The finish line! |
...is not in this post, because I have not received it yet. Apparently when you ship 2Day with Fedex, you are prone to two different meanings of 2Day shipping. The first meaning is two days later. So if you are sent a package on Thursday (which is when my new phone was shipped) you will receive it on Saturday.
As I've mentioned several times here, there is usually one day during the Spring and the Fall where the weather drastically shifts from cold to hot/hot to cold. Today was that day. Last week temperatures were in the mid to high 90's and today temperatures never got out of the 60's. Looks like the Prickly Pear saw it's shadow...
The Very Large Array is a system of dish telescopes that act as one single telescope using the principle of interferometry. In an interesting twist, not only do they all act in unison for one telescope, but combined they are also a part of another interferometric system known as the Very Long Baseline Array, which the Arecibo telescope is also a part of.
Getting to the VLA is quite an easy trip, take I-25 south until you reach Socorro and then take US 60 West until you see giant dishes on the side of the road. It is a 2 hour drive from ABQ, which would make this the most boring day trip ever. Luckily I was on my way home from the Lightning Field and this trip required just pulling over for a pit stop.
This particular day, the VLA was stretched out in a particularly long pattern. Each telescope is movable and the array has several different configurations available to meet the needs of the scientists. Sometimes the telescopes are packed in tight, while other times the telescopes are spread out over many miles. The reason for this is because the distance between the two farthest dishes (known as the baseline) is similar to the diameter of the interferometric telescope (bigger baselines yield less resolution though).
As we approached we could see telescopes for many miles in each direction all pointing toward the NE section of the sky collecting data (it doesn't have to be dark to do radio astronomy!). And I took pictures of the telescopes way off in the distance (there is a slideshow below and I encourage you to look at the full resolution images to see how far away I was when I first spotted the array).
Once you arrive there is a little museum that talks about radio astronomy and what we've learned about the universe because of it. There is a movie that plays that talks about the telescopes (that I didn't watch) and you can go on a walking tour to get up close to one dish, view the control room, and walk around the main campus.
The museum isn't that great and could clearly use some upgrading. There is a gift shop too that has some merchandise (Stef bought a coffee mug) but I didn't find much of it appealing. The walking tour is great though. There are plaques explain the physics of parabolic dishes and as I mentioned above you can walk right up to a dish just to see how big it really is (and it is big!). When you get to the control room you are given a (relatively) bird's eye view of the array and even just the addition 30ft can give you a whole new perspective on the impressive achievements of the telescopes.
Despite how poorly I portrayed the experience, I had a good time at the VLA, but I could be corrupt because I used to be very interested in astronomy, spent a summer at the Arecibo telescope, and enjoy the occasional night of stargazing. I did spend a considerable amount of time taking pictures, just staring at the vastness of the configuration, reminiscing of my time in radio astronomy, and talking to Stef about the work she did at the site (she helped setup the Long Wavelength Array which is a system of arrays of antennas around NM, with one site at the VLA, designed to study low energy signals from space). If you are ever driving to southern NM for a trip or to the Lightning Field, then it is definitely worth a stop to the VLA, because after all science is fun!
Information:
Location: Plains of San Agustin about 50 miles west of Socorro
Website: VLAsupported by NRAO
Free Admission
Rating: Awesome
When you make your reservations for the Lightning Field the first thing you'll notice is the price ($250 per person during July and August, $150 per peson for May, June, and September, $100 per person for students) then you'll notice that the location of the Lightning Field is shrouded in mystery. You are told to drive to the offices in Quemado and from there you will be picked up and brought to the location. The final thing you will notice is that there is a disclaimer that says "A full experience of The Lightning Field does not depend upon the occurrence of lightning..." While reasonable it sounded like the operators were trying to keep visitor hopes down.
Knowing New Mexico weather, I knew that rain wasn't likely and that thunderstorms are more prevalent in late summer (hence my planned visit for Labor Day weekend), but not something to set a clock to. I wasn't too worried about the chance of seeing lightning, but I was hopeful. I was more worried that seeing a bunch of poles in the middle of nowhere turned out to be the most boring experience of my life. I'll get to that in a moment.
The drive to Quemado is about a 2-3 hour drive depending on how fast you go and which way you go. If you start by going east on I-40 you'll be treated to spectacular scenery as you drive through Malpais National Park. If you start by going south on I-25 you'll be treated to a glimpse of the VLA (Very Large Array). I took both routes, going the I-40 route towards Quemado, and then returning via the VLA.
Upon arrival you'll notice that Quemado is a really small town with just a few buildings. You'll also notice that you CAN'T find the Dia office. That's because it is the most run down building in town and has the smallest sign possible. I took the liberty of documenting that for any potential visitors because NO ONE in the Corrales office or the Quemado office bothered to answer the phone with regards to finding the site. So the building below is what the Dia Quemado Lightning Field office looks like.
The next image is the sign telling you that this is the building you want to be at. Yea not too visible...
A man named Robert eventually picks you up from the Quemado office and whisks you away to the cabin that you will be staying in for the night. On this particular adventure it had been raining quite a bit and the roads were very muddy. That made the ride very, very fun (or scary depending on your idea of fun). I have to say this drive was the best part of the trip. Nothing like getting the blood pumping before a relaxing evening on the prairie.
Once you get to the cabin, Robert tells you everything you need to know, how to contact him in case of an emergency, and some safety precautions. Then he drives off never to be seen again, until the next day. From here on out you are free to do as you please. It is just you, the Lightning Field, and in my case 4 other people who you hope won't get on your nerves for the next 24 hours.
The pole grid is literally just a few hundred feet from the cabin, and once you get there you are encouraged to spend as much time in the field as possible. There is a packet inside the cabin with some facts about the construction of the field. Unfortunately I could not find this information on their website (or anywhere else for that matter) but it is rather interesting. It definitely helps you appreciate the scope of the project.
Which brings me to my next point, how is the experience? If you take the Lightning Field at face value it is pretty weak. You are in the middle of nowhere, left alone, with a field of a bunch of metal poles and you aren't likely to actually see lightning strike the field. If you go to the Field with that in mind and never open your mind it will be as exciting as I've made it out to be.
If however you enjoy the outdoors, you spend a lot of time walking around the Field, in the Field, and enjoying everyone you traveled with you might enjoy the experience. I myself did enjoy the experience, but with that said I don't think my life is complete because I've seen it and I don't think I would miss anything if I never heard about it. But let me tell you about my experience (which after this very long intro is really what this is all about)...
Walking around and in the field you definitely get the feeling that there is more effort put into this than meets the eye. It took more than just one person to design the Field and being there really hammers that home. As you touch the poles you realize they are more sturdy than just a piece of metal casually placed in the ground. You look at the tops of the poles and you realize they aren't just regular poles, someone meticulously crafted the tips to be perfect (the fact sheet something about the curve of the tip matching the arc of a 6m circle). You also realize that every tip is perfectly level creating a plane, and that each pole is precisely positioned within a fraction of an inch. Walking around the field you also realize how many poles there are (400) and how long it took to put it all together. Once you consider all that and whatever thoughts about the meaning of life pop into your head, then you begin to appreciate it.
As an idea, I still don't really appreciate it. The Lightning Field in principle still seems silly, I mean it's just poles on a field. But I definitely appreciate the amount of effort that it took to construct such a silly principle. I appreciated the time I spent in nature, I appreciated the time I spent with my girlfriend, and I definitely appreciated the drive out to the Field (and living to tell the tale). So all in all the Lightning Field was a positive experience, plus I got a ton of great pictures.
If you don't like nature, don't enjoy the company of others, and don't like being without your iPhone, then you probably won't like the Lightning Field. If however you do like those things and can appreciate great works of man no matter how pointless they may seem then you will most likely enjoy the Lightning Field. If you do decide to go, definitely convince a group of friends to go as the bonding you will experience will make the entire experience way more enjoyable.
Information:
Location: Hidden NE of Quemado
Supported by Dia Art Foundation
Rating: Awesome
Hypotheses in the comments please.
I'm back from the technological abyss known as Quemado. Tomorrow I'll post the full review of my trip to the Lightning Field. I captured some excellent pictures so stay tuned...
View Larger MapJust letting the world know, in case I end up lost in the wilderness, you will know where I am. This will also be the next stop on the Great New Mexican Adventure. On top of that I will be doing some scientific work. If you want to see what I'm up to read about it over at IheartAnthony's Research, otherwise I'll see ya soon!
I made this poster as part of my official duties as a member of the GPSA (Graduate and Professional Student Association) to make students aware that the GPSA is hosting a social "hour" at Marble Brewery on Sept 6 at 7pm. The catch is that you have to talk to people, but if you like doing that and you like eating free nachos (I wish it were free beer though) then you will love this. Maybe I will see you there?
My mom is running/walking in the Susan G. Komen Race for the Cure which takes place in Central Park, NYC on September 18, 2011 to support breast cancer. I made this t-shirt for her and her friends and all the money that I would normally make from it will be donated to the event. There is nothing that says you too can't support the cause if you can't make it.
IheartAnthony's Research
This officially marks the split of my science and everything else, which has been something I considered for a while. One day there will be no more Randomly Grad Life and this is just the first step in the process, but I promise that day isn't very soon. I will be returning to blogging very soon and when I do I promise it will be spectacular.
I've been really slow on the blog front lately, but I've got a lot on my plate and so the blog hiatus will continue until I can hit a groove with everything in my life. Until then I'll be posting in random fashion and I'll start/continue with this interview I did for a good friend of mine.
Los Alamos is on the map once again because of two main factors. The first is because of the Las Conchas wildfire that has been inching closer to the labs everyday. The second factor is because everyone knows what the labs there do and this is even bigger because of the Japanese nuclear reactor failure after the earthquake and tsunami. Now the news is trying to fear monger and make the nation aware that this could be the great US nuclear failure.
Well if you came here searching Los Alamos fire, Las Conchas Fire, New Mexican forest fires, LANL labs fire, or anything that has the search term fire and something NM related you are in for a rude awakening. The labs aren't going to burn down and there is not going to be a US nuclear disaster right now.
(Disclaimer: I have no knowledge of the contents and practices of Los Alamos National Lab, but I am speaking on behalf of logic and my experience of safety procedures as a scientist). Regardless of what we know goes on up there, or what we think we know, whatever nuclear material is stored up there is underground in hardened facilities to protect the said material from disasters of both a natural and man-made origin. There is no way that if the fire burned the facility there would be a leak of reactor proportions.
Not only that but, in light of the Japan situation, there is no way the US government would allow a disaster of that proportion to happen on American soil this near in time to the Japanese situation. Within 24 hours of the initial reports, the governor of NM called in the NM National Guard to immediately provide support. If the fire were in real danger of consuming the lab, federal support would begin IMMEDIATELY. There would be no wait.
Don't pay attention to the headlines of reports. They all say the same thing, which is something along the lines of "Fire races toward national nuclear lab." If you read the articles themselves they will mention that the labs are near the fire, that the fire has burned a lot, and that the town of Los Alamos has been evacuated. They may or may not mention that the line of contact is at the labs, meaning those fighting the fires are focusing their efforts on protecting the labs and the town.
As I last heard it, the fire was 15% contained and that was last night. Today more support is expected and conditions can only improve. So stay calm, relax, and use your heads. Don't just read the headlines of print or CNN. They are designed to peak your interest in the story, not to be the base of the story itself.
With that said there are a lot of people displaced because of the fire and they need support. Here's how you can help:
- visit http://www.rrfb.org/ and donate money, food, or personal care items
Update: Stef pointed out to me that this is technically bday present number 2. Bday present 1 was a waffle iron with which I will make yummy vietnamese waffles. Yummy!
On this day 27 years ago, I was born. And that means in 3 years I will be 30...
