in singulo: Single Molecule Biophysics

It's all in the swagger

2011-08-01T00:01:00.001-07:00

If I need to explain what this is to you, you shouldn't be reading this blog.

Happy Passover!

2011-04-19T20:15:00.000-07:00

Since we had our seder last night, some friends requested Diana's superb chicken recipe (nobody requested my brisket recipe, though. Sniff.) Reproduced here:

I used Rub with Love Chicken Rub http://store.tomdouglas.com/products/rub-with-love-chicken-rub. If you don't want to order it, you can make a reasonable substitute with 1/4 cup brown sugar, 4 tsp smoked paprika, 4 tsp coriander, 4 tsp garlic powder, and 2 tbsp chinese five spice powder.

Clean and rinse the chicken. Coat liberally with olive oil, then season with spice rub and salt and pepper. Place the chicken breast side down in the roasting pan. Roast for 15 minutes at 350 per pound of chicken. 2/3 of the way through the cooking time, flip the chicken breast side up and coat again with olive oil. Use a meat thermometer to test for doneness- the chicken can be removed from the oven when the temperature reaches 145 in the thickest part of the chicken (between the drumstick and the thigh). Allow the chicken to rest, tented with foil, for 15 minutes before cutt

On This Day In History

2011-04-01T14:18:00.000-07:00

For a few years at Princeton and U of I, I was in the habit of making posters for fake talks and hanging them around the physics department on April Fool's Day. Some of my favorites included:

Applications of Non-Linear, Non-Homogeneous, Non-Solvable Partial Differential Equations

and

Theoretical Biophysics Colloquium

Insane in the Membrane:

Insane in the Brain?

Prof. B. Real

Cypress Hill University

The Journal of Universal Rejection

2011-03-20T19:53:00.001-07:00

http://www.universalrejection.org/

This is so brilliant that I'm actually sad I didn't think of it myself.

"The founding principle of the Journal of Universal Rejection (JofUR) is rejection. Universal rejection. That is to say, all submissions, regardless of quality, will be rejected."

I may dig up "Quantify vs Quantitate" and submit it, but right now the Intarwebs have forgotten it, and I'd need to go back through my old archives to find it.

This Shit Just Got Real

2011-01-19T10:44:00.000-08:00

Because I know you've missed me.

A Discovery with Many Potentially Useful Applications

2010-12-03T07:26:00.000-08:00

Via regs to my inbox (it's not new, but still funny): Medical researcher discovers integration, gets 75 citations

For Hire: LabView coders and optics jocks

2010-11-19T10:00:00.000-08:00

I've been doing some work for a local biotech, and they're currently in need of somebody to do some short-term LabView coding and optics work, like in the next few weeks. It pays well, I just have absolutely no time for it right now. If you do, let me know! This could become a longer-term situation if it works out. The location is in silicon valley not far from Stanford. Struggling grad students welcome!

Graphene? Really?

2010-10-05T12:32:00.000-07:00

Can somebody with more condensed matter background explain to me why the 2004 discovery of graphene is worth the Nobel? It was less than 10 years ago, and although everybody is predicting lots of practical applications, so far there have been none. I presume that it's being used by a lot of people to test lots of theories about 2D electron transport and quantum behavior, but to me that makes it more of a tool for testing interesting theories than an interesting discovery in its own right. Of course, people do win Nobel prizes for tools (laser cooling, for example) but I don't see graphene as being in the same category of importance. Anybody want to tell me what I'm missing?

You call this programming?

2010-09-23T11:52:00.000-07:00

In the past couple of months that I've been learning Java on-the-job (i.e., incorrectly, with no formal guidance), I think I've spent the majority of my time doing the following, in order of how much time I've actually spent doing it:

1) Trying to convert properly between several roughly equivalent types in order to feed data from package X into a method from package Y.

2) Figuring out which package contains what I’m looking for.

3) Figuring out why eclipse is F’ed up.

God Man versus Science Hero!*

2010-09-16T16:58:00.000-07:00

Via BoingBoing

*Note: My views on theology, religion, deism, and atheism are actually complicated to enunciate**, and reference Gödel's Incompleteness Theorem, the problem of induction, and the semiotic fallacy, and are still evolving. I don't really endorse the view of SCIENCE!(tm) being in direct opposition to RELIGION!(tm). I just thought this was a funny cartoon.

**Maybe if you ask nicely I'll write about it someday.

Churn

2010-08-31T08:31:00.000-07:00

PacBio going public in order to raise...$200M? That's kind of a pittance compared to the $300M they already have from VC. Is that a bad sign? I guess I don't really understand the finance side of things.

And, on the heels of that announcement...

Helicos sues PacBio. The last refuge of scoundrels.

In Silico

2010-08-19T13:47:00.000-07:00

In case you've been coming here day after day, wondering why I have stopped posting, and where in the world is Carmen Sandiego, I thought I would update my (rapidly shrinking) fan base with my whereabouts: for almost a year, with the prospect of my funding drying up, and no publication in easy sight, I spent some time taking stock of my options, and deciding what I wanted to do with the rest of my life. And, the fact of the matter is: I was bored. I was unhappy. I really think single molecule biophysics is awesome, and fun, and there's great stuff happening. But I had discarded enough plastic pipette tips to last a lifetime, and was finding it increasingly difficult to care about the rate constant for phosphate release of E. Coli RNA polymerase in the presence of XYZ. Additionally, I had grown to really love the bay area, and didn't want to leave my friends, my girlfriend, and my hang glider behind.

My options, as I saw it, were:

Keep on keepin' on, and try to find a professorship at the University of Wallamaloo, or wherever I could, and hope that things would be more fun and interesting as a mid-grade intellectual at a mid-grade university.
Back out, and try to find another postdoctoral appointment doing something completely different, and hope that, four years down the line, at 38, I wasn't totally burnt out on that as well. I considered computational evolution, or even getting a masters in EE or CS, and seeing where that took me.
Get a real job.

I talked to a lot of people, and received some encouragement from some corners, most notably from Ben Ovryn at AECOM who strongly encouraged me to not give up on academic science. Just as conspicuously, I received no such encouragement from my research advisor, who, when I discussed my options with him, basically shrugged.

I applied for biotech jobs, software jobs, and a professorship at City College of New York, because I thought it would be fun to live there and teach there. I considered taking a year off to write a book, or become a professional hang glider pilot, or both. I thought of opening an artisanal sandwich cart in San Francisco with a friend of mine, because, let's face it, you can't get a decent deli style sandwich in the bay area. In the end, I had a job offer from a high flying biotech startup that would have required me to move to the east coast, and a job offer to work at a friend's software company, and I chose the latter.

So, this is where I am. I'm currently employed as a Forward Deployed Engineer at Palantir Technologies in Palo Alto. The software is incredible, the people are amazingly smart and fun, and my group is mostly comprised of Ph.D.s who left science to try something else, and wound up here. I do a bit of everything: I project manage, I code, I do some outreach, I integrate data, and I sometimes look for new and interesting ways to use our product. I've been here for four months, and it's been pretty much non-stop excitement.

I've learned a lot. First, that there are a lot of really smart people out in the private sector, if you look in the right places. Scary smart people, the kind that academics will tell you don't work in the private sector. Second, I've realized that many of the dysfunctional relationships I had in the academic world were not actually due to my personality flaws, but were largely due to the peculiar culture that tolerates (and in some cases rewards) dysfunctional interpersonal relationships in academia. It's refreshing to work with people who are smart, engaged, enthusiastic, and who genuinely want to work together to create something worthwhile and powerful. I think, to some extent, the archetypal academic interaction is the pissing contest, where people jockey for status, because status is the only currency in the academic world. All other forms of interaction are subordinate to the pissing contest. It's refreshing to step away from that world. And, third, it took me two or three months out of academia to realize how really bored I was with what I was doing. It's not that I think it's intrinsically boring; it's just that it wasn't really driving me to do more and accomplish more, but I had had myself convinced that this was the way to go, that this was interesting because everybody else said it was. With some hindsight, I can see that if I had found it really that fascinating, I would have been eager to get up and get in there to do more. And there just wasn't that drive, and it was making me miserable.

So, I'm here, I'm finally liking what I'm doing, and I'm liking the people I'm doing it with. I'm getting up in the morning excited to come over here and face the challenges of the day. I'm still advising the grad student who's following up on my work a little bit, and I'm even doing some consulting for a biotech startup in Silicon Valley, just to stay in the game for fun. And, if I ever start to get bored with what I'm doing, I'll remember what it feels like, and I'll do something else. I don't know if I'll keep updating this blog again. Now that I've come back and gotten the long-overdue explanation out of the way, I may just post little sciencey tidbits here and there to amuse myself. We'll see.

And, finally, if you're a bit bored or frustrated with academia, you have some programming/technical experience, and you want to work for a company that offers three free meals a day, free laundry, free massages, free beer and cookies, and some of the most interesting and clever people you've ever met, hit me up. We're hiring.

Judge Invalidates Human Gene Patent

2010-03-30T11:48:00.000-07:00

According to the Times, the finding casts doubts on pretty much all patents on human genes. Bad for pharma, good for the rest of humanity.

Worse Living Through Chemistry

2010-03-08T11:54:00.000-08:00

As some people have noticed, I'm not much of a chemist. I would go so far as to say that it's one of my weak points. But this list of "Things I Won't Work With" has to be some of the most interesting and funny reading I've seen in a while. People in my lab tend to freak out about things like acrylamide, ethidium bromide, and beryllium fluoride. I tend to think that as long as you don't ingest anything or get it in your eye, you're probably okay, and shouldn't freak out too much. And, this list really gives you a sense of perspective, e.g.:

You start off by making absolutely pure anhydrous hydrogen azide, which is a proposal that you don't hear very often around the lab, and is the sort of thing that leads to thoughts of career changes...The next step is introduction of the fluorine, and when elemental fluorine is the most easily handled reagent in your scheme, let me tell you, you're in pretty deep

Protons in zeptoliters

2010-03-04T08:56:00.000-08:00

Looking at Ion Torrent's new technology, they are detecting base addition by the release of a single proton. This seemed a bit far fetched to me. I mean, water is constantly in flux between the protonated and deprotonated state, so how could you detect a single new proton? So, a rough back-of-the-envelope calculation (just to prove I can still do it):

Assume that their nanofab chamber volume is about 1 zeptoliter (10^-21L). I got this number from one of Pacific Biosciences' papers, but I'm guessing the scale is quite similar. The concentration of one single hydrogen ion in 1 zL is then:

(1/6 x 10²³)/(10^-21) ≈ 2 mM. That is actually quite a bit! Thought about another way, though, pure water is at 55M concentration, so there are 55M x 6 x 10²³ x 10^-21= 33,000 water molecules in a single reaction volume, so you're trying to detect a single proton against a background of 66,000 possible free protons (two per water molecule.) That makes it sound a bit harder. In any case, it's apparent that it works!

Thanks!

2010-02-24T16:27:00.000-08:00

Just wanted to close out the BPS week with the following graph showing my traffic over the past 30 days:

That big jump there is when the BPS put my blog on the front page. Quite impressive! Thanks to everybody for visiting! Now that the BPS is over, I hope you stick around!

BPS Tuesday Reflections

2010-02-23T17:42:00.000-08:00

I had lunch today with a PI whose lab I applied to several years ago when I was looking for postdoctoral positions. I eventually settled on Steve's lab, but he's one of the nicest guys I've met, and we serendipitously got together at the meeting and had an hour or so to chat. It really gave me a lot of perspective on where my career has come from, and where it's going, the latter question being on my mind a lot lately. I think, if I'm coming away from this conference with anything, it's a commitment to do what I want, and what I think is interesting, rather than what other people think I should think is interesting, and damn the consequences. The fun science isn't usually the easy science, and the science that conventional wisdom holds to be "important" or "interesting" isn't always fun. If Gordon's Law of Maximal Uselessness holds true, and science fails 90% of the time, you're better off having fun than trying too hard to impress people, because your attempts to impress people will probably be futile anyway, and this way, at least you had fun!

I wandered around some posters, listened to some talks about chromatin, and am going to head off for dinner, then back again for the superresolution talks. I have some business at Stanford in the middle of the day that can't be moved around tomorrow afternoon, so I might just stay at home tomorrow, rather than come up for two hours and go back. So, keep your pants and your powder dry, science aficionados, and don't miss your flight!

Intarwebs Scarcity

2010-02-23T11:53:00.001-08:00

The lack of wifi in the conference rooms and the relative difficulty of getting on the conference center wifi even in the lobby is making this a bit rough. I'm back to phone blogging.

William Shih's talk on DNA origami was fascinating, but I didn't really get a sense of how likely some of these more complex structures were to form. They're pretty though!

After an excellent dinner with colleagues, much beer, and watching the American curling team get trounced by the Chinese, we came back for the national lecture, but got shunted into an overflow room. It seems like the conference planners just didn't plan for this vig of a conference.

The national lecture was good though. Roger Tsien really is a great speaker, and his work on genetically encoded EM reporters is really great.

Tonight there are three simultaneous sessions from 4 to 6 all of which I wan to attend: Biotechnology, Genome Organization, and Force Spectroscopy. Argh.

At The Chieftan with Block Lab!

2010-02-22T18:30:00.000-08:00

Thermo Fisher Makes $6B bid for Millipore

2010-02-22T14:09:00.000-08:00

Via my father, oddly enough (he's a transactional attorney, not a scientist, so I guess this is the closest our lives come to overlapping):

Feb. 22 (Bloomberg) -- Thermo Fisher Scientific Inc., the world’s largest maker of lab instruments, made an unsolicited takeover offer of about $6 billion for Millipore Corp., according to a person close to the situation.

More here.

On a more positive note

2010-02-22T10:45:00.001-08:00

I'm a bit of a curmudgeon (actually, I'm a lot of a curmudgeon) so it's easy for me to complain, and as a postscript, I thought I'd say some nice things:

The talk at imaging and spectroscopy on mNeptune looks like it will be incredibly useful. It's a new fluorescent protein that just sneaks into the water window. You can excite it with 633 nm, and detect it at 650, allowing you to do intravital imaging while avoiding hemoglobin absoprtion. I suspect many people will find that very useful.
Two different talks on superresolution imaging of neurons are starting to show the real promise of superresolution imaging. The attempt to use it to trace all the neurons in a brain sample looks very ambitious, and I appreciate ambitious. Of course, the problem is it's sloooowwwww. If you have to fix the cell, why can't you use EM? That's a genuine question, by the way. Why can't you just do EM on brain slices and trace neurons that way, with way more resolution than you can get with any fluorescence technique? There must be a reason this doesn't work. Are they hard to stain with EM probes? Do they degrade rapidly under EM? Inquiring minds want to know.

BPS Day 3: Monday, must be Paris

2010-02-22T10:16:00.000-08:00

Finally found 1) a seat, 2) an outlet, and 3) an IP address (the Moscone center wifi seems to be pretty overloaded. You'd think a famous important science blogger would be able to get an IP address, but I guess the hardware doesn't distinguish.)

Some thoughts on last night's single molecule workshop:

The workshop was chaired by Steve Quake, and the first talk went to one of his colleagues who basically used the time to demonstrate the commercially available sequencing machine that Steve's company, Helicos, has on the market. He talked about the science behind it, but it wasn't really a "workshop" insofar as he didn't demonstrate single molecule techniques that you could do in your lab. It was a promotional session for a self-contained commercial product for sequencing. I think this was in pretty poor taste. Aside from that, he spoke very highly of their read lengths, topping all of 35 bases. Steve Block very pointedly asked what he thought the upper limit on their read lenghts were, and the speaker started waxing about the biochemical limitations. When Steve pressed him for a number, he said, I think, 100 base pairs (though I might have misheard, and he may have said 500. But if he said 500, I don't believe him anyway.) The reason that Steve pressed him, of course, is the fact that Pacific Biosciences is now boasting an instrument with several hundred base pair read length, which suggests that the Helicos instrument has a very limited future. Of course, Pac Bio doesn't have an instrument on the market yet, and Helicos does, and there are a lot of advantages to being first to market. So who knows.
Zev Bryant's talk was interesting. He described double headed mutants of myosin that could be made to switch directions at will, and described processive motors made out of myosin heads that had basically protein logs between them. I'm surprised that you get processivitiy out of such things, but I guess if the ATP is low enough, the heads spend most of their time bound to the actin, so they're naturally processive. I'd like to see optically switchable myosins, and I'm sure he's working on it. Genetically encodable optical switches seem to be a growing theme, I'm seeing a lot of it all over the place here.
Adam Cohen's talk was a bit silly, I think. He used glass lenses on top of coverslips to create highly confined spaces, 1 nm up, between the glass and the lens, and looked at proteins diffusing. Things undergo confined quasi-2D diffusion, so they stay in the field of view longer without being tethered. But most people are trying to develop assays that get molecules further from the surface, to minimize surface effects. Here, the surface effects are huge, and this is sold as a benefit. The technique didn't solve any particular problem, it didn't present any new science, and it presents a host of new problems. On the other hand, at least it was fun, and fun is good.

At Hotel Utah with Assorted Weirdos

2010-02-21T19:00:00.001-08:00

New, Notable, Emerging

2010-02-21T16:13:00.001-08:00

The 'New and Notable' talks were quite interesting, and invigorated me a bit. It's always fun hearing about cool applications of new technology. I learned a lot, especially about optics from the talk on adaptive optics imaging.

I noticed a peculiar schizophrenia of mine though. When I hear about new techniques, I usually think, "That's cool, but what is it good for?" But when I hear about biological problems approached with established techniques, I usually yawn and think, "Nice, but not novel." I guess I'm looking for the rare hybrid of novel new technology being used to solve interesting problems, which in some sense is what biophysics is about (to ab experimentalist.)

Now at 'Emerging Single Molecule Techniques.' Guess we'll see if there are any unicorns to be had...

Day 2 morning: a minor complaint

2010-02-21T10:46:00.001-08:00

I got here in time this morning to see part of the nucleic acids/protein interaction talks. It was packed,with people standing along the walls. I stepped out, and when I came back, I was told by one of the Moscone droids that the room was full and I wasn't allowed in. That seems like pretty poor planning.

'New and Notable' is getting under way...

BPS2010 Day 1: Laptop Fail

2010-02-21T01:10:00.000-08:00

My laptop is failing to boot, gentle reader, so my BPS blogging may have to ve via my Palm Pre, and hence less verbose that is my wont. I'll try to work around it. Just letting you know.

Walking towards the conference center this afternoon, I was reminded of my first BPS, also in San Francisco. It was an unusually warm February, I was young and excited about science, and, arriving from the midwest's gelid winter, I remember feeling like this was one of the greatest cities in the world. Ten years or so on, and I'm no longer as fresh faced, but I still think San Francisco is my favorite city in the US. And considering that this may well be my last BPS, the symmetry is elegant.

The first talk out of the gate at the flurescence subgroup was Steve Blocks which was...not about fluorescence. I'm not sure why Steve was asked to speak (and neither was he, really), and he stuck mostly to the mechanics of the kinesin cycle. I think this was a particularly odd choice, since the fluorescence subgroup is usually technique-heavy (as the name implies). I think talking about optical trapping in general, as a technique, and comparing it's pros and cons versus fluorescence, would have been more interesting to the group at hand.

In the middle of the next talk, the power went down for about ten minutes. Nice work, Moscone center!

Eric Greene's work with "DNA curtains" looks very promising for biotech and research applications. (I'll include links and pictures later when I can get to a working PC.) By microfabricating onto the coverglass surface, they're able to make very reliable distributions of stretched DNA molecules, both with and without flow, and control the density very carefully. Looks very exciting!

During the cookie break, I hobnobbed with all the usual suspects: Ahmet Yildiz (a co-conspirator of mine in Paul Selvin's lab, now setting up his lab at Berkeley), Michael Woodside, Ibrahim Cisse (previously at Taekjip Ha's lab at UIUC and now post-docing in Paris), and Sterling Churchman (postdocing at UCSF) among others. Lab space, construction, the hiring of grad students and postdocs...all very exciting!

I stuck around to see the Young Fluorescence Investigator Award, which was given to JW Borst. In the past, the YFIA has generally gone to people associated with UIUC and/or the Laborator for Fluorescence Dynamics in some way or another. But since Enrico Gratton has moved the LFD to Irvine, I think it has diffused somewhat. I didn't know anything about Prof Borst's work before today, and was not totally blown away. He's using fluorescence lifetime imaging (FLIM) to look at interaction of different factors in the cell. It looks interesting enough, but it didn't seem particularly novel to me. Maybe I'm missing something.

I was also surprised by the choice of Dan Axelrod for the Gregorio Weber prize. Dan has certain made a significant contribution to fluorescence through his introduction of TIRF microscopy. But I seem to recall that Dan left U Michigan very abruptly about six or so years ago, leaving a few people in the lurch, and has been laying low in California since then, apparently doing experiments out of his basement. I guess it was an easy commute for him at least. He's still listed on the U Michigan web page as having emeritus status. Who knows.

The Block lab, past and present, gathered together for dinner after the afternoon's talks, and then half of the lab returned to go see the evening motility talks (by Steve Rosenfeld) and the other half went over to the W Hotel and continued to drink in earnest until around half past midnight. We had a good time. Tomorrow morning (if I get up in time): protein-nucleic acid interactions ahoy!

A New Era in Information Overstimulation

2010-02-18T12:41:00.000-08:00

I'm going to be experimenting with this thing the kids are calling the "IntarTwitters". I'll be Twittering about the meeting here, so you can follow me from talk to talk, listen to my approval and/or disapprobation at various talks, and possibly even engage in some two way (or more way!) dialogue about the meeting. Let's give this whole technology thingy a whirl!

A Bit About Me

2010-02-15T18:01:00.000-08:00

Thanks to the BPS, I will shortly have some new readers (hello, new readers!) so I wanted to give you a bit of an update about me, who I am, where I am, and where you'll find me at the BPS meeting this year.

I'm a postdoctoral fellow in Steve Block's lab at Stanford (he of the famous cappuccino machine) where I have been working on developing combined optical trapping and single molecule FRET, and using that to study ribozyme structure and function. My graduate work was done at UIUC in Paul Selvin's lab, mostly doing single molecule fluorescence (although we did do a bit of FRAP and confocal microscopy back when I was starting.) As the title of the blog suggests, I'm pretty interested in single molecule biophysics.

At the BPS on Saturday, I'll be attending the fluorescence subgroup (always a reliable gathering of UIUC alumni, and in particular people who studied under Enrico Gratton and/or Gregorio Weber), as well as sticking my head in the door at the motility subgroup. I don't do any work on motility personally, but just about everybody I've ever worked with does, so you kind of get exposed to it by proxy.

During the meeting proper, I'll probably be attending mostly the platforms on RNA, fluorescence techniques, and force spectroscopy. But I do occasionally like to show up to random talks that I don't know anything about, and see if I can learn something. Unfortunately, given Sturgeon's Law, these talks usually don't teach me much, and I wind up falling asleep.

The other thing I will be doing a lot of is drinking. I find that conferences in general are about 50% science, and 50% schmoozing, and the schmoozing almost always takes place over drinks. To that end, I will have friends in town, and I am going to make an effort to go out on Saturday night. If all goes as planned, I'm probably going to hit the lounge at the W Hotel near the convention center and catch up with old friends and new. Feel free to stop by!

P.S. I'm also currently looking for jobs! See the link on the right for my CV!

Meet your New Blogging Overlord

2010-02-03T09:33:00.001-08:00

That's right, fans and fairies, I've been chose to be one of a select cadre of 2010 Biophysical Society Bloggers. I will be blogging live (LIVE I TELL YOU!) from the 2010 BPS meeting right here in San Francisco*. As a results, I will be endowed with great super powers. And an iPod nano, apparently.

So, buckle your seatbelts! It's going to be quite a ride! In a couple of weeks, when they formally link my blog to the BPS home page, I'll write a formal introduction to the poor lost souls who haven't seen the true destructive power of this fully operational blogostation. Until that time, I should probably try to get back into the swing of things and, you know, BLOG about SCIENCE once in a while.

*Yes, I am not technically in San Francisco. I am in Stanford, CA, a whole 40 minutes away by car. But if you're reading this on the intarwebs, I'm probably a lot closer to San Francisco than you are.

BPS blogging

2010-01-06T09:02:00.001-08:00

Before everybody and their brother forwards me the announcement about the Biophysical Society looking for bloggers, I already send them an e-mail. Blogging has been light lately, due to a combination of holidays, data collection, job searching, and ennui, but I'll definitely at BPS, and I blogged BPS last year for free without any incentives. So all ya'll may be hearing from me again soon.

The Fat Man Cometh

2009-11-13T13:09:00.000-08:00

The Fat Alberts Man, that is. Just came back from hearing Bruce Alberts speak. He talked in general terms about his early career, his work on Molecular Biology of the Cell, his time as president of the National Academy of Sciences, and most recently about his work as editor of Science magazine. He had some interesting things to say, although nothing really ground-breaking. He generated a lot of good will by talking about his early graduate work and about how it was a complete failure, and how he literally failed his thesis defense and was required to go back and do another six months of research. One of the things I found most interesting, though, was his repeated insistence that young scientists need to come up with new, novel ways of doing things, and not just repeating the type of work that others have done before them, and about how he personally wanted to use the journal Science to encourage that sort of thinking. But this seemed to me to be highly ironic. Journals like Science and Nature, have a system of pre-peer-review editorial review, where they reject a large fraction of papers for not being interesting enough, or sexy enough, or relevant enough, irrespective of the quality of the science. This is actually the complete antithesis of what he seems to be striving for, and I think it's well accepted (at least among people that I know) that major journals play a pretty active role in discouraging experimentation on innovative systems with innovative techniques, because the journal editors just won't understand why it's interesting or important if it strays too far from the known corpus.

Compare this with the talk I heard at the Science Commons salon recently, by Peter Binfield, the managing editor of PLoS ONE. PLoS ONE operates in exactly the opposite fashion: they will publish anything, as long as the science is sound. They then rely on the community to rate the work based on relevance, importance, or whatever else they deem interesting, sort of like Digg or Reddit. The question, of course, is whether the Intarwebs-at-large is a better judge of what's interesting, useful, and innovative than the editors of Science. I'm not really sure. I'm not even sure that "interesting" is a useful metric. But, "interesting" is what interests people, so it will always have some relevance.

Pair Sciencing?

2009-10-16T22:51:00.000-07:00

I attended the Science Commons Salon last night and spent some time talking to intargoogles celebrity Joi Ito. He was very interested by my comments about the lack of a "Journal of Failed Experiments" and the question about why such a journal doesn't exist (even though most people agree it would be useful) and what cultural, institutional, and scientific barriers prevent it. The topic also touched on some questions about what Science(tm) could learn from Silicon Valley. Joi seemed to believe, as an article of faith, that making science more responsive to outside interests (money, medicine, engineering, et cetera) would be a good thing, and I was not entirely convinced of that, being a bit of a purist. I often like to point out that J.J. Thomson did not have cell phones and computers in mind when he discovered the electron. But I actually didn't broach this topic with Joi, preferring to try to glean from him what I could, rather than argue about Science(tm) versus "science".

One interesting idea I came away with was the thought that, if you look at most of the fast growing high tech firms, they gave up long ago on having extended 9AM meetings in which people put up PowerPoint slides and discuss their latest progress. This management model would be considered downright ossified in places that practice methods like "agile programming", and "extreme programming". (In the latter, for instance, 15 minute "stand up" meetings (nobody is allowed to sit) are the norm, to keep the meetings on track and short, and to keep people on the important stuff.) But, strangely, our project management style is exactly this, interminable 9AM meetings filled with PowerPoint slides and people falling asleep (literally, in some cases.) I started to think about some alternative ways to structure research, at a very basic level, and was thinking about an extension of the "pair programming" methodology, of which Joi seemed to be a big fan.

Imagine, if you will, the following: a research group is divided into two groups, 1 and 2. Alice, Barbara, and Cathy are in group 1, and Arthur, Bob, and Carl are in group 2. Each person is the lead on one project, so Alice has her own project, Bob has his own, et cetera. During the first week, one person from team 1 and one person from team 2 get together to work on the team 1 projects. So, for instance, Alice and Arthur work on Alice's project, Barbara and Bob work on Barbara's, et cetera. During week two, they switch, and work on the team 2 project with the same partner. In week three, now, they rotate partners, but go back to the team one project. So, now Alice works with Bob, Barbara works with Carl, and Cathy works with Arthur. Week three is for team 1 projects, and week 4 for team 2 projects. And so on, and so forth.

What would be the practical consequences of this arrangement? Well, for one thing, everybody is invested in everybody else's project, and everybody gets their name on every paper. One of the impediments to collaboration in the lab is the question of lead authorship: if I give over too much control to somebody else, I might lose my slot as lead author! But this system preserves lead authorship, which, although artificial, is extremely important for job searching and funding. The principle on each project is still the lead author. It gives everybody in the lab a broad range of experience working on a lot of projects, and it allows people with fresh eyes to contribute to projects, by bringing new perspectives, which is often what's needed. And, by maintaining the rotation, people stay up to speed on their peers' projects, and don't need to be retrained too often (hopefully.) I'm curious if this would be a workable lab environment. I can see pitfalls (what if Alice and Bob hate each other?). And, also, this organization isn't idea, because Alice never gets to work with Barbara. But, there's probably some simple permutation that could get us around that problem. In any case, I think it would be a bold experiment. If I ever have my own lab, it would be something I genuinely think I'd like to try.

You have mistaken me for someone who cares

2009-10-01T13:31:00.000-07:00

From: "Lynda T. Carlson, Director, Division of Science Resources Statistics"

Dear Matthew Paul Gordon,

Help! The survey is closing soon, and your perspective is important to us.

The National Science Foundation (NSF), Division of Science Resources Statistics (SRS) really needs your input on the survey of early career researchers with doctorates or equivalent degrees, including postdoctoral researchers (postdocs).

Dear NSF:
I asked you for some money a bunch of years ago, and you said "Go shove it, kid." So, allow me to return the favor. You can take your survey and stick it where the sun don't shine.
Sincerely,
Dr. Matthew P. Gordon, Ph.D.

Bad Bob! No biscuit!

2009-09-25T17:18:00.000-07:00

I like Bob Park's "What's New" newsletter, but he can be pretty shrill at times. And the times that I've written him to point out errors, I've gotten a cursory reply. If he's going to play the "I'm a physicist so I'm smarter than you" card, he should at least be, you know, correct. To wit, in regard to cell phones not causing cancer, we are told today, "[A]ll known cancer agent act by breaking chemical bonds, producing mutant strands of DNA." Uh, Bob, have you ever heard of HPV?

Arbitrary Friday: Happy New Year

2009-09-18T13:37:00.000-07:00

I'm spending today cleaning up and RNAse purifying a PCR, so it's a lot of waiting and not a lot else to do until I get back on the optical trap. In the meantime, thoughts turn to Rosh Hashana, the beginning of the Jewish new year on the lunar calendar, which starts this evening. The high holidays tend to make me lonely, and a bit homesick. I don't know a lot of Jews in the bay area, my immediate family all lives in Chicago, and my extended family lives on the east coast, so I usually spend my high holiday time in a contemplative mode (read: alone.) I go to the campus Hillel, I follow along with the prayers, and I think about my relationship to the ineffable, and how that relationship can help me be a better person.

I say "the ineffable" because my relationship to God qua God, which is to say, God as a disembodied entity, has changed radically over the last twenty years or so. In my youth (said the sage, as he shook his gray locks) I was a devout adherent to the Reform Jewish movement. I went to Jewish summer camp, I had my Bar Mitzvah, and I had a strong and personal relationship with God. When I prayed, it was fervently, and with intention.

But, as much as it sounds like a cliche, 10 years in the relentless, ruthless pursuit of empiricism at all costs has had its toll on me. I now think of myself as somewhere between deism and agnosticism. The more I learn about the natural world, and the more time I spend with my brain in a mode of empirical observation, the less room there seems to be for a God in the universe. At the same time, it's obvious that "God", as an idea, serves a purpose to people, giving them hope and meaning, so there's an incentive to believe in such a thing, an incentive that has nothing to do with what can be deduced about the world. Occam's razor thus cuts God to pieces*.

So, then why not atheism? Why settle for agnosticism? A few reasons. First: Gödel's Incompleteness Theorem puts limits on what we can deduce from purely mechanistic logic. No matter how ruthless our logic is, there are still statements that can be notionally outside of our ability to prove them. It's obvious that the Occam's-razor-appoach to God (i.e., why believe in God if we don't need one?) is not a proof, and one can readily construct ideas about God (such as deism) that are beyond our capacity to prove or disprove, at least within a logical framework. Does this mean that I believe in God? No. But it means that I accept that I cannot prove that there is none. And given the very idea of God as an interloper and creator of human affairs, it is not unreasonable to suppose that such a being might hide himself behind layers of obscurity.

On the other hand, logic itself is a system of belief, and it also has its dogmas, such as induction. We base most of our "logical" conclusions on induction, but induction is really only a rule of thumb, and one that we can't even prove: try proving the validity of inductive reasoning without using induction. (Go ahead, I'll wait here.) So, our instinct that logic is the only reasonable mode of interpretation of the universe is itself suspect. It tends to produce useful results, so I'm willing to stick with it for most things. But, once again, I'm not willing to rule out the possibility that there are other modes of understanding our experience and our universe that might not also be valid. As an example, we have an entire emotional life that is not governed by logic. We believe things that we have no reason to believe, we frequently know with great certainty things that are provably false, and we make errors in judgment all the time because of our feelings. We can, at a fundamental level, understand this by logic, by understanding the evolutionary processes that got us to this point, and by understanding the neurological processes that underlie these feelings. But that doesn't make the feelings any less real or urgent: you can explain lust as a biochemical reaction, but it doesn't make me want what I want any less. And I'm here, inside this meatbag, trying to make sense of a world distorted by these chemical reactions, and logic sometimes doesn't help with that. A different paradigm is sometimes needed.

So, all that said, what do I do on the high holidays? What do I do when I'm sitting there, being urged to repent my sins, and trying not to fall asleep? Why subject myself? The answer is kind of the same as the above: I'm still inside this meatbag, and I still crave meaning. I still need direction. And whether that direction comes from a book purportedly written by an entity, or from a feeling that I owe certain things to my fellow man because of some comsic duty, or because Dogar and Kazon command it of me, I have to find it somewhere. To do otherwise is to give in to nihilism, which may be logical, but isn't very satisfying. And, deep down inside, when the cantor intones the age old melodies of Kol Nidre, asking God to forgive me for the vows that I cannot keep, I can feel the stirrings of that truth, that urgent feeling I had at age 13, that there's something outside of myself that talks to me from without, but also from within, and that asks me to think of my life as part of a giant Rube Goldberg contraption with a singular end, to improve the world. And I am invited to examine those pieces, and see which of them are helping, and which are hurting. And to make a choice. And for who do I make that choice? אהיה אשר אהיה‎...I am that I am...

*Perhaps this is what was meant by Hattori Hanzo in Kill Bill Part 1, when he says, "If on your journey you encounter God, God will be cut" by the superb craftmanship of the sword he produced. The relentless pursuit of perfection in engineering leaves no room for chance, or God, if every factor can be accounted for and controlled. The perfect sword will indeed cut God.

The Elements

2009-09-15T11:34:00.000-07:00

I know I posted another video from this new They Might Be Giants science album, but this one is just too awesome to not post (via BoingBoing):

Not to be confused, of course, with:

Science is Real, Yo

2009-09-09T07:57:00.000-07:00

Finally, a use for carbon monoxide!

2009-08-28T11:11:00.000-07:00

Via my friend Don Weber*, via Slashdot, via Science (the journal, and, I suppose, thence via science, the epistemological pursuit), comes a report from IBM Zurich on imaging single surface adsorbed molecul es at the atomic level** using an AFM tip functionalized with carbon monoxide atoms. Imaging single adsorbed molecules, not in a lattice context, is very difficult. In this case, they were directly imaging Pauli repulsion, which is pretty neat. It's interesting to think, sometimes, that the fact that your coffee cup doesn't pass through the table is basically just the Pauli exclusion force at work. And here it is, again, writ very small. I don't know what the implications for biology are, since interesting biological molecules are generally not planar. But interesting work nonetheless. c.f. this work on im aging single spins using an AFM.

*Before I went to grad school, Don and I worked at a now defunct software company together in Chicago called Geodesic Systems, and shared an office with two other people. I once gave a lunchtime talk on biophysics, back when I had never given any talks and didn't really know how to give a decent talk, and Don fell asleep in the middle of the talk. His comment upon mailing this to me was, "I didn't even fall asleep while reading it!"

**More memories: We did an AFM lab when I was an undergrad, with a "teaching" AFM, trying to image a HOPG lattice. The AFM was suspended from the ceiling using bungee cords as a method of noise dampening. Unfortunately, in the other half of the lab, people were trying to do Compton scattering, which involved moving lead bricks around. We would sit, holding our breath, as line after line of the image would form, and then somebody on the other end of the lab would drop a lead brick on the ground: BANG! And the image would do the optical equivalent of a phonograph needle squealing on a record. Fun times, fun times.

Weekly roundup

2009-08-20T13:47:00.001-07:00

Steve Quake sequences his own genome, one molecule at a time (Nature Biotechnology)
SMB writes up the Aspen conference on SMB as a guest editor at Current Pharmaceutical Biotechnology, hosting a special issue on single molecule biophysics. Steve's essay is free, but the rest of the articles you have to pay for, I guess, or. At least, Stanford doesn't give me online access. (Your guess is as good as mine as to what any of this has to do with pharmaceuticals.)

Meanwhile, in other parts of the scientific world...

Arbitrary Friday: Argh

2009-08-14T17:39:00.001-07:00

My experiment may be made of fail, but at least there's funny stuff on the intargoogles to cheer me up, with the knowledge that there are some really dumb people out there. Some of my recent favorites:

There I Fixed It

Passive Aggressive Notes

DNA synthesis with ATTO dyes?

2009-08-04T15:30:00.001-07:00

Does anybody know if there's a DNA synthesis company that will make oligos modified with ATTO dyes? I've looked at IDT, Midland, and Sigma-Aldrich. I want to do a quick-and-dirty experiment which will be easier if I can just buy a pre-modified oligo, and if it works, I can then maybe buy amine-modified oligos and label my own.

Arbitrary Friday: The Easiest Nobel Prize?

2009-07-31T14:02:00.000-07:00

Let's say you're 18, you're just entering college, and you have decided that your life's goal is to win a Nobel Prize. You don't care which, you just want to taste that sweet Swedish gold. So, what's your best bet? Which is the easiest prize to get?

I'm going to rule out physics, chemistry, and medicine right off the bat. That may be my biophysics science bias showing, but seriously. I don't think you can count on any of those as a good bet. The odds are really astronomical, even if you're fucking brilliant to begin with.

I'm also going to rule out economics, because it's a fake Nobel prize. We're talking the real thing here.

That leaves us with Literature and Peace. I've done my share of writing (including several chapters of a never finished book, and two ten minute plays, one of which was a musical about the life of the Danish astronomer Tycho Brahe, titled Uraniborg), and it's really hard. And I've gotta say, when I read really good writers, I'm usually just left drained, unable to comprehend how they quite do it. Like Michael Chabon, or David Foster Wallace. You can't emulate that, you can't fake it. Writing is hard, certainly hard in a different way than physics, but I think it's even harder to get good at than physics is. I think you pretty much have to be born a writer, there's no two ways about it. You can't just work really hard and get really good at it.

So, that leaves us with Peace. I would say, based on the history of the Nobel peace prize, Peace is definitely the way to go. If Yassir Arafat and Henry Kissinger can win the Nobel peace prize, I think it strongly suggests that there is a serious dearth of people out there trying hard enough, and there must be a few openings. In fact, if you consider the aggregate contribution to overall peace, I think you would probably rank higher than Yassir Arafat if you simply consistently opened doors for old ladies. And let's not forget Mother Teresa, that sainted old lady who won the Nobel peace prize for denying the poor the one thing that would have really actually helped them, which is to say birth control. So, given some of the less than stellar contributions made by these people, I think you've gotta put your money on the peace prize. There seem to be a few different ways to go about it, but I think that if you're genuinely interested in trying to bring peace to the world (or at least genuinely interested in trying to win a Nobel prize), and aren't too worried about material wealth, the field is pretty much wide open. You just pick a cause and run with it until you're out of breath, and hope that people notice.

Sick Day

2009-07-29T12:15:00.000-07:00

[Editors note: This got stuck in my draft queue and didn't get uploaded. I'm feeling better today, but am still having some stomach issues. Hopefully I'll be okay by the weekend.]

Been at home clutching my stomach for most of the morning, but I'm now sitting upright and eating cereal, and think I might be able to go into the lab in the afternoon. Meanwhile, I share with you: Acoustically driven programmable liquid motion using resonance cavities, in PNAS.

One of the problems with microfluidics is that, no matter how micro you make the fluidics, you still need big computer controlled pumps to run everything. The above paper has attempted to solve this problem in a very elegant fashion, using resonant cavities to apply pressure, with the pressure controlled by externally generated sound waves, allow you to control your microfluid device with a veritable symphony:

Of course, if you had six or eight of these things in your lab, it might quickly turn into a cacophony, a la the acoustic memory scene in Cryptonomicon.

Recent Literature

2009-07-28T15:01:00.000-07:00

Some recent entries of interest in the single molecule literature:

A former colleague of mine, Anne Gershenson, now a professor at Brandeis, has written a review of single molecule enzymology for Current Opinion in Chemical Biology. It holds up as an example the work on HIV-RT done by Elio Abbondanzieri, formerly of the Block lab, now at the Zhuang lab. But it's a good examination of the state-of-the-state-of-the-art.
The Bustamante lab has published new work on optical trapping of frameshifting psuedoknots in PNAS. People have been working for some time to understand what exactly is the origin of psuedoknot frameshifting efficiency, with mixed results, but figure five is where the money is here, strongly suggesting a relationship between unfolding force and frameshifting efficiency. I haven't read the whole thing, though, so I will reserve further comment.
Helicos has a paper in Nature Methods reporting on a "virtual terminator nucleotide" for sequencing. These appear to be nucleotides that can reversibly terminate elongation, like a di-deoxy nucleotide that can be un-di-deoxied, if you will. This ensures that the next base added in a single-molecule addition assay is really only a single base, but that further bases can still be added afterwards, elegantly fixing accumulated off-by-one errors.
Also, Hagar Zohar from the Muller lab at Berkeley writes in with news of their new web page of links to resources for single molecule biophysics, put together by a grad student organization called the CharISMA Idea Lab. I added a link on the right as well.

Arbitrary Friday: Danger Edition

2009-07-10T11:35:00.000-07:00

People often think of scientists as men in lab coats and wire rim glasses living lives of quiet desperation. While the quiet desperation is true in most cases, the idea of scientists as nerdy milquetoasts has remained pretty well embedded in our cultural consciousness (see, for instance, the execrable TV show "Big Bang Theory" for countless examples), in spite of a plethora of counterexamples. Richard Feynman was of course famous for his womanizing, lock picking, adventure seeking, and numerous practical jokes. The late great David Schramm was a 240 pound red haired demon who climbed mountains and tragically died at the fairly young age of 52 while flying his own single engine airplane. But, even apart from the famous and infamous, scientists that I know are generally a sensitive, artistic, and adventurous lot. They play piano, banjo, and rugby, they dance the salsa, they climb mountains, and that's just counting the people in my lab.

On the other hand, scientists are, by and large, a careful lot. They calculate, they consider, they assess risk, and they eschew it in most cases. I grew up in a Jewish household in the suburbs, where danger seemed to be all around, where taking the bus to the mall seemed fraught with opportunities for death and dismemberment, and where even a jungle gym presented terrifying, murderous possibilities.

But, lately, I've definitely taken a turn for the more dangerous. For starters, as bland as it seems, moving to California was an adventure for me in a lot of ways. I was moving far from my family, far from any of my friends, to a place I had never lived, with a lot of distinct cultural differences, and with very little context to guide me. And, in a lot of ways, my Grand California Adventure has been a fantastic success. I've taken all sorts of risks and experienced all sorts of new things (some of which are not really appropriate for discussion here.) But, I have also definitely started to incorporate danger into my life in more tangible ways.

About six months after moving here, for instance, I finally went and bought my first motorcycle, a 1997 Harley 883 Sportster (which you will find pictured to the right.) Hardly the most dangerous motorcycle in the world (it has trouble getting above 80 miles an hour), but a significant departure for me. Of course, I didn't just go out and buy it: I started even before I moved by taking a course from the Motorcycle Safety Foundation, and simultaneously studying up on motorcycles, riding, and what kind of bike I should get as a beginner bike. (Motorcycles for Dummies suggested the Sportster as a good intro bike, and I've been happy with it in that respect, although I'm starting to feel like it may be time to get something with a bit more oomph, that handles a bit more solidly.) Which is to say, I didn't plunge into it with abandon: I carefully selected and pursued my choice of danger, and mitigated the unecessary risk.

Not long after that, I was driving up to San Francisco, and passed by Fort Funston. All of a suddent, I realized that hang gliding was not just something that people did in movies: I was in California! There were mountains! If you had the desire (and the money!), you could fly. And so I got myself a block of lessons, and, well, the rest is history:

So, the question I ask myself is: why? Why live dangerously? My parents certainly ask me that. Is it just to impress the babes? (I hope not.) Is it because I'm some sort of thrill junkie? Honestly, I don't feel like the risks I'm taking are that unreasonable in a visceral sense, even if they are statistically more likely to result in me dying in a horrible accident than if I were to not pursue them. Therein, though, lies the answer, I think. William Gurstelle, and author and recent guest poster on BoingBoing, was discussing his new book, Absinthe & Flamethrowers: Projects and Ruminations on the Art of Living Dangerously. He hypothesizes that "the golden third", living in ways that are more dangerous than average, but still short of making pipe bombs out of match heads, is correlated with overall happiness and contentment. Fair enough, it seems like I'm toeing that line. But, still: why? Why does it make me happy? Why do it?

I don't really know the answer, but I suspect that there is an element of control involved, or, more precisely, lack of control. Most of us spend a lot of time exercising control over our lives, and, as discussed above, scientists want to control everything. (Even our experiments are sometimes called "controls"!) But sometimes, it pays to let go of that. It pays to intentionally step out over the ledge and look over. Because, not everything in life can be controlled. And if you spend all of your time in your bubble of control, in your circumscribed safe space, then what the hell are you going to do when the shit hits the fan? How are you going to cope? How are you going to deal when you're not in control? I've gotten into near accidents on my motorcycle; I've had the wind shove my glider around and nearly lost control; and it's pretty damn scary. But, your blood gets pumping, and your heart takes over, and you learn a little lesson about yourself, and how you react, and you internalize that. Flying is fun! But sometimes you crash, and in life, the decisions with the most importance almost never happen when you're in control, they happen when things are flying off the handle, and you don't have the time for sober reflection.

Total internal pedantry

2009-07-07T14:58:00.000-07:00

Glancing over some new articles on single molecule stuff, I came across the following curious title:
"Ultrastable combined atomic force and total internal fluorescence microscope." Surely, this had to be a mistake, but no, the article actually uses the term "total internal fluorescence". Now, certainly, I have been accused of being a pedantic word nerd at times, but this construction really irks me. For those of you still scratching your head, the correct term is "total internal reflection fluorescence microscopy", or even just "total internal reflection microscopy." But, the the term "total internal" refers to the reflected excitation light, not the fluorescence emission. "Total internal reflection" (TIR) is actually a quite common phenomenon in physics and has applications far beyond fluorescence microscopy (for instance, fiber optics are based on TIR.) "Total internal fluorescence" on the other hand seems like it would be useless: the fluorescence is totally internal, and never gets out, so what's the signal?

Just to make sure I wasn't smoking crack, though, I checked around the intergoogles a bit. On Pubmed, for instance:
"total internal reflection fluorescence": 629 hits
"total internal fluorescence": 11 hits

But, this hit in particular startled me. It lists in the references:

E. Sund and D. Axelrod, “Actin dynamics at the living cell submembrane imaged by total internal fluorescence photobleaching,” Biophys. J. 79, 1655–1669 (2000).

If no less a luminary that Dan Axelrod, the GODFATHER of TIRFM, could use the term "total internal fluorescence", then clearly I was way off base. Fortunately for me, clicking through the link reveals that in fact the authors had misquoted the title of the paper! The actual title, as you might imagine, is "Actin dynamics at the living cell submembrane imaged by total internal reflection fluorescence photobleaching."

In other news, I have heard tell around the water cooler that certain Block lab associated people have been selected for various Biophysical Society awards at the 2010 meeting, but since the BPS website doesn't have any info on it, I'll keep a lid on it until a formal announcement is made.

OMG ROTFLMAO LOL NIH NCBI HIV TAR

2009-07-02T13:11:00.000-07:00

Via boingboing: from the land up north, we get NCBIROFL.COM, a collection of published bioscience papers that are probably only slightly more absurd than your own research. Although I must point out that they're a bit behind the curve: the June 30th entry has already been widely hailed, having won the 2003 IgNobel prize in physics.

Watch Yer Mouth

2009-06-17T13:20:00.000-07:00

I read way too many political blogs, so although only tangentially relevant, here are some interesting tidbits I read today:

First, over at Crooked Timber (one of the few blogs where I bother to read the comments), Michael Bérubé offers a writeup of some developments in free speech in higher education. He points to the case Hong v. Grant, which basically states that a university can administratively punish a professor for job-related speech which is not related to teaching or research (committee work, for instance.) Hence, this chilling letter from UC Davis to the Faculty Senate:

According to recent court rulings, your speech and behavior in job-related duties as a public employee rather than a private citizen have no First Amendment protection. This means that disciplinary action may be taken against you (including dismissal) for statements you make in the course of your employment. According to recent court rulings, your speech and behavior in job-related duties as a public employee rather than a private citizen have no First Amendment protection. This means that disciplinary action may be taken against you (including dismissal) for statements you make in the course of your employment. Any activity performed on the job falls within this purview. According to the recent court rulings, speech and actions in shared governance activities are certainly not protected...In light of the present deep economic recession and dramatic cuts under discussion at UC Davis, faculty participating in shared governance are in a position in which they may voice strong views and concerns that could lead to lawful but punitive reaction by the administration, including denial of merits and even dismissal. Given the legal and policy realities at hand, we highly recommend that you use caution, restraint, and judgment in your speech and actions in all job-related duties.

So, as Eric Rauchway put it, "If I follow the logic correctly, Hong is obliged to participate in the administration of his department. But the definition of 'actively participate in the interworkings and administration of his department' appears here to be, 'say only those things which won’t lose you a merit increase.'"

I find this particularly interesting as a scientist because we tend to think that "academic freedom" debates mostly apply to people like Ward Churchill, and not to scientists. Not so! Now you can get canned for being a loudmouth at your departmental committee meetings. And there are no shortage of loudmouths in the sciences, that's for sure.

On a completely unrelated note (except for the fact that it's about politics): The Great Paul has pointed up some very interesting legislation:

On Monday, Sens. Jon Kyl (R-AZ), Mitch McConnell (R-KY), and Pat Roberts (R-KS) introduced the “Preserving Access to Targeted, Individualized, and Effective New Treatments and Services (PATIENTS) Act of 2009,” a new bill prohibiting Medicare or Medicaid from using “comparative effectiveness research to deny coverage.”

This really just leaves me speechless. The War on Science continues unabated. At least the Republican Party is consistent on that front.

More 3D tracking

2009-06-09T16:51:00.000-07:00

Another entry in my ever growing docket of 3D tracking techniques: A nice paper in Nano Letters from Yale Goldman's lab on a new method of 3D single molecule tracking using a system they call "Parallax". Their data is very nice, and they manage to achieve something that I was actually trying to do in grad school: visualize 3D helical motion of myosin VI around an actin filament. The technique is very nice, and is a somewhat simpler realization of a system proposed earlier here. It utilizes a splitting of an image into two halves with slightly different optical path lengths, which causes the images to move differentially in the X-Y plane based on their localization in the Z plane. Worth a read! Their use of mirrors instead of prisms is quite clever.

Focus on Microscopes

2009-06-04T13:00:00.001-07:00

Nature has five articles focusing (ha ha) on new types of microscopy, including Stefan Hell's STED (with brief mentions of PALM and STORM), and Sunney Xie's foray into Raman spectroscopy. They also have the gigantic (a 13 meter electron microscope) down to the tiny (the 3 cm microscope-on-a-chip). Written in conversational style, nothing too heavy. Some fun summer reading!

If I Only Had a Brain

2009-05-26T16:24:00.000-07:00

Via the always awesome Makezine blog*, this is an interesting article promoting "The Importance of Stupidity in Research." It's worth a read. The premise is that research, actual honest-to-goodness groundbreaking research, involves a lot of flailing about in the dark and feeling stupid, and people tend not to be accustomed to that feeling, because it's the opposite of how you're supposed to feel in your classes, where you're supposed to always know the answer.

This meshes well with a truism that I've been known to spout, which is, "If it was easy to do, somebody would have done it already." At least, for really novel and groundbreaking research, that's true. I suppose there's plenty of fill-in-the-gaps type of stuff that people have to do, the sort of stuff that requires labs full of technicians and grad students using time-honored techniques and a lot of elbow grease. But I think that's almost an entirely different category of research.

On the other hand, the converse of this sentiment was expressed once by Albert Young** when I was at Princeton, and he said, "90% of physics is just not being stupid."

*Speaking of which, if you're in the bay area, you should definitely attend the Maker Faire this weekend.

**Remembering Albert's name took a Herculean effort of googling. Basically, I had to remember that he was a classmate's thesis advisor (to whom he imparted the wisdom), and then I had to find a catalog of Princeton theses and look up that classmate's thesis. Albert is now apparently at NC State in the physics department, according to the intarwebs.

Dueling acronyms

2009-05-25T10:19:00.000-07:00

Courtesy of Greg Snyder:
SHRiMP: Accurate Mapping of Short Color-space Reads

Not to be confused, of course, with:
SHRImP: Single-molecule high-resolution imaging with photobleaching

It's all in the placement of the capitalization (apparently.)

I also note that the first author of the SHRiMP paper is one "Stephen Rumble," who I can only assume is a third cousin once removed of Stephen Quake.

Nanorobotique

2009-05-15T12:01:00.001-07:00

From Laboratoire De Nanorobotique (how freaking cool does that name sound?) at the École Polytechnique de Montréal:
Magnetic sensing bacteria are used as an external propulsion system to direct a solar-powered microsensing device. No published details yet as far as I can tell, but that is really awesome.

Non-Blinking Quantum Dots

2009-05-12T14:58:00.000-07:00

Quantum dots are cool. They're bright, small, and they don't photobleach. The problem: they blink, and the "off" state can last a long time. Certain preparations can reduce the blinking, but personally my luck with this has been pretty middling. Now, apparently, a group of researchers has produced non-blinking quantum dots. All I can say is: wow! And: when can I buy them?

Arbitrary Friday: Sandwiches

2009-05-01T16:48:00.001-07:00

Thinking lately about what it is I want to do with my life when I get out of here, and I have been thinking about things like professorship (hard to get in any place I want to live), biotech (I don't really want to spend the rest of my life at the bench), software (my first real job, and always a convenient fallback), VC (will six figures soothe a tortured soul?), and other possibilities. But, six or seventh down the list, I think I'd like to open a sandwich shop. Not really, of course. There's no better way to lose your shirt than to open a restaurant. But, I do love sandwiches. I mean, I lurrrrrve me a good sandwich. And I would love to spend my days perfecting the art of the sandwich, serving them to others, and making the world a better place by making it more sandwichy. Here are some of my favorite sandwiches:

Primanti Bros in Pittsburgh. They put the french fries in the sandwich!!!
Bat 17 in Evanston. Man do they make a good sandwich. Everything is toasted and smothered and cheesy and goddamn now I'm hungry.
The Bread Company in Urbana, IL. Their swiss bread is amazing, and they make a really mean tuna salad.
Jimmy John's. As fast food goes, these guys are the best. They use very high quality ingredients, and their selection is great. I would take a Jimmy John's over a Quiznos or a Subway anyday. Or over almost any other fast food, for that matter. And they're also headquartered in Champaign-Urbana.
Lutticken's at Stanford. Lutticken's isn't amazing, but it's certainly the best you can get locally. They don't do sandwiches well here on the west coast, in my opinion, but Lutticken's gets points for their excellent Dutch crunch bread, their very tasty meatball subs (both meatful and meatless), and for being locally owned.
Hoagie Haven in Princeton. Whenever I go back to Old Nass, I try to stop by The Haven for a peppersteak hoagie. They are legendary, for good reason. Fried on a greasy grill, and stuffed into your eager mitts at 1AM. Nothing satisfies like a Hoagie Haven hoagie.
Mr. Beef in Chicago. Italian Beef is to Chicago what Cheesesteak is to Philly, and nobody does it better than Mr. Beef. Portillo's can stuff it, they don't even come close. One glance at the wall covered in the media coverage and the unsolicited celebrity endorsements is enough to convince you that the place has a well deserved reputation. (I've read two different interviews with Chicago native Joe Mantegna in which he extolls the virtues of Mr. Beef, apropos of nothing, he just feels the need to tell the world.)

I think you get the idea. I have to go make a sandwich now.

STEAMpunk Imaging

2009-05-01T13:52:00.000-07:00

Holy Fast Fourier Transform, Batman! This is some seriously fast imaging: Serial time-encoded amplified imaging for real-time observation of fast dynamic phenomena. They claim imaging with 440 ps shutter time. Yowza! This is a pretty complicated engineering feat, but they dumbed it down into a really cute movie:

Basically, the way to understand this is that the two main time limiting steps with CCD imaging are CCD readout time and the inherent dark background, which requires you to have a minimum number of photons per image to not get swamped. The latter has been addressed in recent years by the advent of on-chip amplification, but it's still not perfect.

STEAM imaging (as they call it) is quite different. It takes a short laser pulse, which has an inherently broad spectrum due to the fourier transform of the pulse, and turns that spectrum into a 2D "spectral shower", where different colors map onto different parts of the image. The reflected light is then re-collected, and turned back into a pulse such that different parts of the spectrum arrive at different times. Then, each pulse carries the 2D image information in the time varying intensity of the pulse. This is amplified optically using a doped fiber (very high bandwidth, no electronics required), and it can be read out by a single pixel photodetector. The pulse intensity variation is mapped back onto a 2D image for human consumption.

Obviously, the system as designed can't be used for fluorescence. But for bright field imaging of metal particles (which they demonstrate in a microfluidic system) it's excellent. They image quite large particles (10 - 20 microns), and I'm not sure how well this would work with smaller particles. But, they suggest that this is intended specifically for biological applications several times in the paper, so I presume there's no intrinsic limit in that sense. I'm waiting to see if this will be available commercially any time soon.

WolframTF?

2009-04-28T11:21:00.001-07:00

Wolfram Research is pimping a new, as yet unavailable offering called Wolfram Alpha. I honestly have no idea what he's getting at here, but I'm intrigued. He doesn't give any concrete examples of how this would be used, so I have no way of knowing whether this would even be relevant to my life, but, in classic Wolfram fashion, he seems to suggest that it will be relevant to everybody's life and will, in time, become the most important thing in the universe. However, via Crooked Timber, I see that there is going to be some sort of demo/webcast/talk or something, so maybe it will become more clear at that point.

As a bit of background: I did my doctorate at U of I, where Steven Wolfram is nominally an adjunct professor in the physics department (although I never, ever saw him in the building.) Wolfram, the company, is based in Champaign, and Wolfram, the person, gave a CAS/Millercomm lecture when I was there about NKS. It was interesting, as it went. People have very diverging opinions about it, and they're closely linked to their opinion about Wolfram himself, who is a very brilliant but very polarizing personality. (He published his first paper on high energy theory when he was 16.) Nigel Goldenfeld, who I consider myself privileged to think of as a friend, thinks very highly of Wolfram's work. But, he also published a paper which tends to seriously undercut some of the premises of Wolfram's magnum opus, A New Kind of Science. Then, there is also this famous review/screed from a fairly well informed player, albeit one with an axe to sharpen, titled A Rare Blend of Monster Raving Egomania and Utter Batshit Insanity. It's a very amusing read, and offers an interesting perspective, but it is tainted with a heavy helping of argumentum ad hominem (which is what makes it so much fun to read.)

In any case, you are welcome to draw your own conclusions, but I predict, if the past is any guide, that Wolfram Alpha, whatever it is, will be interesting, in a parochial sort of way, but will be far from game changing.

UPDATE
Here's the video. I'll have some more comments after I can carve out an hour and a half to watch it.

Arbitrary Friday: Why Dating Sucks for Scientists

2009-04-24T11:57:00.000-07:00

Seeing as how I've let the professionalism of this blog slip pretty far already, I figured I'd continue the trend, with due credit to Michael Bérubé's fantastically witty blog, and institute an "Arbitrary Friday" policy in which I get to blog about whatever I feel like on Friday. For our inaugural installment: why it sucks to try to date as a scientist, or, How I Learned to Stop Worrying and Love Masturbation. (I warned you that the professionalism was going south.)

I am a 32 year old man. My brother, sister, and most of my contemporaries have long since settled down and started procreating. But, here I am, still prostituting myself to the gods of interwebs dating, trying to find "The One." Or even just "The One who doesn't annoy the shit out of me the first time we meet." So, are there special impediments to dating as a scientist? (Or, can I at least tell my mother that there are, so I appear to have some sort of excuse?) Sure! Here are a few:

Time. I know everybody's busy, and there are plenty of jobs that require just as much time commitment as being a researcher. But scientists have a special relationship to time. We have to work when the instrument is available. We have to be there to watch our gel. We have to come back in at 9PM to take the cells out of the incubator. Want to go out Wednesday night? Sure! Except that I have trap time Wednesday night, and then I have to be in at 6AM to start an incubation. Trying to set up a date around these constraints is like trying to color between the lines, whereas love is like scribbling all over the page with a red sharpie. They're not compatible. You can have your cells, or your romantic weekend in Tahoe, but not both.
Location. Most universities are in shitholes. Take it from me: I spent seven years in Urbana, IL. Dating in a town like Champaign-Urbana is not pretty. That's why most graduate deparments with a reasonable gender ratio are incestuous to the point of nausea. By year three, everybody has slept with everybody. (Luckily, the physics department generally doesn't have that problem, since the gender balance is so skewed that "dating" within the department is only slightly better than "dating" in a prison.) And, if you're a postdoc, kiss even that goodbye. I don't take classes, I don't get invited to student functions, and if I did, I would be the old man in the room anyway. But even here, in Palo Alto, which is a cosmopolitan mecca compared to Champaign-Urbana, location is a problem. You live in San Francisco? Sure, I only live a 40 minute drive away (if it's not rush hour.) Wednesday night? Sure, I can take off from work at 7, meet you there at 8, we can spend all of two hours together, and then I can go home. Oh, that's assuming I don't have the trap that night. (See "Time" above.)
Social Retardation. This one kind of speaks for itself. Because, seriously, if you had an ounce of charm, would you have majored in physics? No, you'd have been having way too much sex in college to have the time to study for that kind of shit. This one does get better with age, though, fortunately. Silicon Valley, for all its flaws*, is full of women who think nerds are hot. But, the average Silicon Valley nerd is a BSE working at a software company, and, as nerd cred goes, the physics Ph.D. is pretty much the trump card. This helps compensate for the fact that, at parties, I would rather stare at my drink and try to calcuate the Reynolds number in my head than risk the potentially devestating consequences of talking to a woman I've never met.
Inability to Lie. I know this is one of my problems, and I think it's a problem for scientists in general. Example from a recent date: a girl tells me she likes acupuncture. The correct response would have been, "Oh, that's interesting." The response I gave: "Acupuncture is bullshit." She gamely tried to describe her positive experience with it, to which I responded, "Yeah, well, the placeob effect is very powerful." She said, "Well, I guess we'll just have to agree to disagree." This, for a normal person, is a red flag to change the topic as fast as possible. Not for yours truly, though! I proceeded to explain that there is no empirical evidence supporting acupuncture, no scientific model for how it should work, and basically tell her that she is wrong, wrong, wrong. Why would I do this? Simple: I cannot tell a lie. Faced with a factually incorrect statement, I am constitutionally incapable of letting it drift off into the aether uncorrected. Other things I am unable to lie about: how much I like you or don't like you, how much I disliked the restaurant that you chose, how annoying your best friend is, and how much I want to sleep with you. (On the up side, I don't really want to date somebody who thinks acupuncture is for real anyway.)

These are a few of the special circumstances facing scientists as they go off into the dating world, I think. I'm sure there are others I'm not thinking of at the moment.

*The huge imbalance in the male:female gender ratio being the most obvious. The usual trope about dating in Silicon Valley, from a woman's perspective, is "The odds are good, but the goods are odd."

Ow, The Stupid! It Burns!

2009-04-23T00:09:00.001-07:00

The further exploits of our favorite single-molecule-biophysicist-turned-political-appointee, as he tries to explain "science" to the primitive denizens of Beltwayistan.

Kick Your Ass with Science

2009-04-15T09:54:00.001-07:00

Hey homies, I know it's been a while since I rapped at ya, and I have no excuse. Just postdoctoral life taking its toll. Plus, hang gliding season is here, and I've been excited about that. But I stop by this humble blog to present you with two offerings. First, via Nature Methods, single molecule structures:

A new generation of X-ray sources known as X-ray free-electron lasers (XFELs) is being developed, and the first source, at the Stanford Linear Accelerator Center in the United States, is expected to be up and running as early as mid-2009. Researchers believe that these brilliant lasers, which come with up to a billion-dollar price tag, will facilitate single-molecule structure determination. "We think that these X-ray lasers are going to transform structure determination in the way that lasers transformed spectroscopy about 40 to 50 years ago," says Abbas Ourmazd, a physicist at the University of Wisconsin, Milwaukee.

I'm still waiting for my table-top water-window x-ray source so I can do single gold nanocrystal tracking with x-rays.

Second, via Pharyngula, Kick Your Ass With Science:

Overheard in the lab this afternoon

2009-03-07T17:07:00.001-08:00

A (non-scientist, non-academic) lab visitor, getting a lab tour, upon meeting a graduate student and hearing that he was in his third year: "Oh, so you only have one year left!"

BPS: Home again, home again, jiggity jig

2009-03-04T11:36:00.000-08:00

Went to the emerging single molecules technologies platform today, and caught the last four talks or so. The Pacific Biosciences presentation was very impressive. As a byproduct of their sequencing technology, they were able to measure a large number of interesting rates and parameters on the elongation activity of T7 DNA polymerase, and produced statistics very similar to the ones our lab has produced on RNA polymerase about sequence dependent pausing, for instance. One of their big innovations is the development of these dNTPs with fluorophores on the end of the phosphate. It seems to me like rATP with this kind of fluorophore could be very useful for general biophysical studies, and I wonder if they would consider making it available to the wider community (at a price, of course.) We certainly know enough people at PB to find out.

I headed back to the hotel, packed up, grabbed some lunch, and headed out to the airport, but I got bumped off the flight in exchange for a free round trip ticket (not like I was going to go into the lab after getting back anyway). I got put on a later flight at 6PM, so with four hours or so to kill, instead of sitting at the airport, I called up the airport Hilton and got them to send around the courtsey shuttle. It's much more pleasant than the airport, and I'm currently ensconced in an easy chair in the lobby, about five minutes away from the airport, with a pile of papers that I printed out at my hotel, and wifi. Could be worse. Now the question is: where should I go with my free ticket? Suggestions?

BPS, Day something or another

2009-03-03T08:00:00.000-08:00

Tuesday, must be Paris. At the "Emerging Single Molecules" talk, I think I saw the first thing this morning that actually really impressed me. Steve Chu's group is trying to push the limits on single molecule colocalization. The approach is pretty much the standard two-color co-localization system, but with some very high tech stuff to bring it as close to the theoretical limit as possible, including:

Active stabilization of the optics to prevent image drift
Active stabilization of the sample to keep it in the optimal part of the field of view
Calibration of CCD non-homogeneity to average out errors due to pixel-to-pixel variations

They demonstrated an accuracy of about 0.2 - 0.4 nm, which is pretty amazing.

Thompson et al has been cited and mentioned specifically in every talk so far.

Somewhat interesting talk on single molecule SEM on gold nanocrystals by Yuji Sasaki. I believe I heard him speak about this work when he was doing this with X-rays, and obviously this is a lot more convenient. Unfortunately he only had a very tiny amount of control data, but it was a 30 frame 10 ms time resolved image of tethered brownian motion. Seems cool. I actually thought about doing this some time ago with SEM, but since I know nothing about SEM, didn't really know if it was feasible. This looks promising, but complicated.

UPDATE: At the microfludics/nanofab workshop. Bob Austin's talk was really something, talking about microfluidics devices for separation using a really novel method, what he calls "bump arrays". Very neat stuff, some very cool pictures and movies. In typical fashion, Bob spent a lot of time talking about the Navier-Stokes equation in excrutiating detail, probably just to piss off the biologists. I studied the N-S equation in great detail when I was in his lab, and even I had some problems following his point at times, but the results were indisputably amazing. Some videos available here, but not as cool as the ones he showed, they don't really convey the gee-whiz factor.

BPS, Day 3

2009-03-02T06:11:00.000-08:00

Got some quick dinner last night after the afternoon session and went to hear the single molecule workshop, hear Richard Ebright and Paul Selvin speak, but then cut out early to have a drink with Steve Block, Arne Gennerich, and Michael Diehl. My head has taken a definite turn for the worse, and yesterday was a long day on only 4 hours of sleep, so I slept in a bit this morning. Lessons learned so far at BPS this year: never ask people, "So, are you up for tenure yet?"

UPDATE:
Back at the hotel, waiting for my college roommate Garf to come pick me up for dinner. I attended some of the sessions on intrinsically disordered proteins, but was not really impressed. How would one assay for protein disorder at the single molecule level? That's one problem I'm starting to think about. Saw some neat posters, there seem to be a lot of people combining optical trapping with fluorescence in one way or another. Once again spent more time schmoozing than actually looking at posters. Had lunch with an old friend of my dad's, Peter Ford at MIT. He was one of the people who inspired me to go into physics in the first place (he was a central character in my college admissions essay), and it's always good to see him. He took me to Sel de la Terre, which was fantastic. Highly recommended.

BPS, Day 2

2009-03-01T07:49:00.000-08:00

Gah, was out late whooping it up with the Block Lab, first at East Ocean City Restaurant (colloquially referred to as "Illegal Seafood"). We ate one of these, among other things:
We then went out drinking more.

I have a head cold and didn't sleep well last night, so I'm functioning on four hours of sleep and a lot of coffee. I did make it for the 8:15AM session, and ran into pretty much the whole Selvin lab (past and present) at Jeff Reifenberger's talk on his work at Helicos. Then I went over to the RNA folding session.

Saw some very interesting stuff this afternoon on HIV RNAs, and then came down to the optical spectroscopy session, and dear Lord it is packed to overflowing with people who want to hear about STED, STORM, and all that jazz. Literally, there are people sitting in the aisles.

UPDATE
Lunch with Ziggy in Chinatown, then back for posters. I usually don't last more than 45 minutes at the posters, I have such a short attention span, with all those people around, but this year I was there for a good 2 - 2.5 hours straight, there were so many people to talk to. Saw some old friends, and met some interesting new people, saw some good science, though nothing that totally blew me away.

Worst poster title:

Worst excuse for a poster EVAR:

Arrived at BPS

2009-02-28T08:46:00.000-08:00

Free wifi at the convention center, huzzah. Got a workout in this morning, and am going to split my time between the fluorescence subgroup and maybe duck into the intrinsically disordered proteins subgroup for a bit. Most of the rest of the Block lab will probably be at the motility subgroup. Then, Block Lab dinner tonight with current and former Blockheads.

UPDATE
Kind of disappointed with the biological fluorescence subgroup, the talks this afternoon were very technical and not terribly interesting, to me at least. Skipped out a bit early before the business meeting, and ran into some old UIUC LFD people (back when the LFD was at UIUC.) Also bumped into Anne Gershenson (former Selvin lab postdoc now at Brandeis) outside the intrinsically disordered proteins subgroup. One thing I'm finding is that people who I haven't seen in a couple of years need to look at my nametag because they don't recognize me with short hair, sans glasses and 20 unneeded pounds (c.f. here). But the up side is that people I don't care to talk to I don't even need to worry about! They won't know it's me anyway.

UPDATE 2:
Dave Piston's talk on the history of fluorescence microscopy was very entertaining ("From Pond Scum to Single Molecules.") Apparently, the foundation for most of the superresolution technologies that we've seen recently were predicted in a paper in 1932. Dave said at the end of the talk before taking questions that he was afraid that somebody who had been at a 1908 meeting that he referenced might come forward to correct him about something, at which point Watt Webb took the mic (natch.)

BPS ahoy!

2009-02-25T15:42:00.001-08:00

That's right kids, it's time for the 53rd Annual Biophysical Society Meeting! I may do some live blogging while I'm there, but my proposed itinerary (with some overlaps that I will negotiate in real time) can be found here. Some of the highlights (in my personal, highly myopic opinion):

My former colleague from the Selvin lab, Jeff Reifenberger, will be giving a platform talk on his work with Helicos, Steve Quake's company (8:15AM Sunday)
Lots of talks on superresolution microscopy at the imaging and optical microscopy platform on Sunday morning.
A Sunday workshop on Advanced Single Molecule Fluorescence Techniques in Vitro and in Vivo, featuring Richard Ebright, Paul Selvin, and Jeff Gelles.
Bob Austin will be giving a talk at the Nanotechnology/Microfluids workshop, which is surprising since, as far as I can recall, he almost never comes to BPS. So, that should be interesting.

There will be tons of interesting stuff, of course, and I'd be interested in hearing other peoples' opinions about what not to miss! Feel free to post comments with your thoughts.

iTrap

2009-02-24T10:33:00.000-08:00

From Hands-on with optical tweezers: a multitouch interface for holographic optical trapping:

I was scanning this paper for some sort of scientific justification. Near the beginning, they say, "The widespread deployment of multiple-trap optical tweezers..." Really? I'm in the optical tweezers field, and obviously it's a different part of the field altogether, but I seriously have my doubts that these instruments are widespread. I don't even know what they're used for. I looked around Arryx's web site, and found:

Because our technology can use multiple laser beams at low power to hold an object, it is ideal for handling cells and other sensitive objects and materials. The BioRyx 200 system can be used to collect specified types of cells from a mixed suspension, manipulate cells for enhanced viewing, measure cell-cell interactions and cell-object interactions, and hold sample material for further investigation or isolation.

Okaaaayyyy...I don't do cell biology, but I don't know any labs that do that have one of these. But, whatever, they've been in business for a while (I even know people who work at Arryx), so I'll give them the benefit of the doubt. But "widespread" may be pushing it a bit.

The other bit of justification was:

We believe that the capacity for true real-time independent control of numerous
simultaneous traps, coupled with visual feedback directly beneath the user’s fingertips, besides providing increased experimental throughput and faster training of the operator, will open many doors in interdisciplinary research. For example, this system could be used in studies of motile cells, or single-cell microsurgery.

Cell motility studies with optical traps, like this one from 1989? I don't mean to sound like a playa hater, I understand the gee-whiz factor, it's pretty neat. But, let's just say that I'm glad that this was done in the UK, beacuse I would hate to think that they were spending my tax dollars on it.

More on imaging single spins

2009-02-19T15:12:00.000-08:00

Dan Rugar spoke on Tuesday about their new work on imaging single spins, a topic I've blogged about before. He provided some interesting new data, as well as some interesting benchmarks. Right now, they can detect about an attonewton, but the force from a single nuclear spin is closer to about 10 zeptonewtons (1e-20), so they're still trying to get the resolution down to the single atom level. (Their previous work on single spin detection was on electron spins.)

The main way of driving the noise down is to use ever higher field gradients. A normal medical MRI uses a field gradient much less than 1 tesla/meter, but by using teeny magnets, they can get about 5 megateslas/meter, or about 50 Gauss/nanometer. It's still not quite good enough, though, and apparently they are not sure why they're not getting better field gradients. The gradients are off from their calculations by about an order of magnitude, for unknown reasons.

He did show some nice images of single tobacco mosaic virus particles:

But the 3D scan shown here contains about 8000 points, at 1 minute per point, so it required about 135 hours to collect! His comment about the time, though, was interesting: if you're talking about getting full scale 3D images of every single atom in an object with atomic resolution, and the ability to resolve chemical species, then the current technology you're competing against, X-ray crystallography, has a time scale of several months to infinity. So, 135 hours isn't so long to wait.

Speaking of Gauss: Steve Quake is now apparently blogging for the New York Times as a guest blogger. Check it out. His first column described the life of an academic researcher for those outside of the field, and his next column explored the divide between pure and applied sciences, in which he compares himself to Archmides, Gauss, and Lord Kelvin.

On the home front, I've been recently thinking about giving it all up and opening a sandwich stand. Or, perhaps, when I finish here, getting a degree in ECE from Stanford. Honestly, I think I'll do just about anything to stay out of the workforce until at least 2012 at this point.

Super Duper

2009-02-05T11:23:00.000-08:00

I just stuck myself in the thumb with the Hamilton syringe that I use for loading radioactive RNA into gels. Hopefully I'll get some cool super power as a result. But it was hammerhead ribozyme RNA. Does that mean I'll turn into a human/shark mutant hybrid with the capability of breathing underwater and tearnig people apart with my super powered jaws? I hope so, beacuse that would be way cooler than turning into a human/viroid mutant hybrid. That would just suck.

Obamania, 2004 edition

2009-01-28T11:18:00.000-08:00

Apropos of nothing, I just wanted to post this photo for fun. Back in 2004, when I was at the University of Illinois at Urbana-Champaign, working on my PhD in physics, I was president of the Graduate Employees' Organization, IFT/AFT local 6300. Our union represented the approximately 1500 teaching assitants and graduate assistants, but a lot of the benefits we negotiated for (like healthcare improvements) extended to research assistants as well, so we really represented the whole graduate student community. We had just inked our first contract after 18 very long months of tense negotiations, and celebrated by suing the university for violating the dues collection provisions of the contract (they claimed that their transition to a new payroll system made it impossible for them to actually abide by the contract that they had so recently signed, but a little bit of legal leverage did wonders for their abilities to collect our dues.)

At about that time, a young and energetic state senator had just swept the Democratic primary for US Senate (against one of my father's law partners, no less), and due to a recent scandal involving the Republican candidate and Seven of Nine, was poised to become the junior Senator from Illinois. The union office got an urgent call from his campaign manager (a guy who I recall went by "Rocket"). Apparently, the Champaign County Dems needed a university group to reserve the ballroom at the Student Union, because non-student groups couldn't make such reservations, and would we be so kind as to handle it? I had heard Obama speak a few weeks before, when we were lobbying the state lawmakers in Springfield with the IFT, and he delivered a great address to the group, the details of which I can't remember now. All I remember was that he seemed electrifying. I dashed off to the Union and reserved the ballroom, and he showed up, and gave his stump speech to a packed room.

After the event, we gave him a t-shirt, I got to shake his hand, and he posed with us. If you look closely, you can see my face (with glasses and long hair, ah graduate school!) in the back row, two faces to the right of the now President of the United States. And that, dear children, is the day I met Barack Obama.

Reviews of single molecule protein folding

2009-01-27T16:31:00.000-08:00

Two review papers on studying proteni folding by single molecule FRET, in two journals, by two giants, in one month. What are the odds? I shall have to add these to my always-growing "to read" pile.

Uli Neinhaus, Single-molecule fluorescence studies of protein folding
Bill Eaton, Protein folding studied by single-molecule FRET

Incidentally, I was drawn into the field by the Levinthal paradox (like many biophysicists, I suspect), and I did my undergraduate thesis work in Bob Austin's lab on microfluidic mixers for studying protein folding. So, the physicist in me always hankers a bit to return to the protein folding problem, even though the field is pretty much saturated, and it's unrelated to my current work. Bill Eaton always loomed large in my mind, like a demigod almost, because of those formative years, and I sent him an e-mail when I was shopping around for postdocs. He actually replied and told me that he would love to have somebody with my experience in single molecule fluorescence, but that he didn't have the fundnig at that time. So, it was a no-go.

On a totally unrelated note: I know everbody is looking for jobs right now, but I have two close friends looking for employment in the private sector. One is postdoc with a lot of experience in genomics and single molecule fluorescence, and one soon-to-be-minted PhD studying cancer bio and the cell cycle. The latter is looking mostly in the bay area, the former is open in terms of location. Both are people I would highly recommend for their dedication, their patience, and their intellgience. It's hard out here for a pimp these days, so if you have any interesting leads, feel free to forward them my way, and I will forward them on!

Technique of the Year: Superresolution Microscopy

2009-01-15T13:53:00.000-08:00

Nature Methods has selected as their "Method of the Year" superresolution microscopy, encompasing both optical approaches (STED, 4Pi) and labeling methods (PALM, STORM). I've blogged a lot about superresolution microscopy, its ins and outs, advantages and disadvantages, so I'm glad to see that I've been backing the right horse in terms of impact.

A minor (and very self-absorbed) quibble I will point out: In his review article Microscopy and its focal switch, Stefan Hell cites Norbert Scherer's paper on NALMS, but doesn't cite my paper on SHRImP. The papers are almost exactly the same and came out in the same issue of PNAS, except that ours appeared first (i.e., it was a lower page number) and was submitted several months before theirs.

Happy New Year!

2009-01-13T10:22:00.000-08:00

Hola Amigos, I know it's been a while since I've rapped at ya. I don't really have much of an excuse, since I spent most of the holidays here in the lab and, unlike most of the Block lab, I didn't attend the Single Molecule Biophysics conference at the Aspen center. (For those who are interested, you can see the race results from the conference ski race sorted by best handicapped finish here. Steve, who grew up skiing in the Swiss Alps, placed third.)

As for me, I spent a very frustrating few weeks trying to eliminate RNAse, and I think I found the source, finally, but it was a hair pulling few weeks which left me drained and uninterested in blogging, or doing much of anything else besides consider new career options. Fortunately, due to the miserable state of the economy, my other choices were "soda jerk" and "trust fund brat", so I was forced to continue along my chosen career path, and I'm still here. Bill Scott said to me a couple months ago that a scientist is like a human diode: you go through months, sometimes years of miserable and utter failure, for a few moments of brilliant success (if you get that far), and then it's back to failure. This lifestyle does not mesh with my personality very well, unfortunately, and sometimes I feel like I'm being driven slowly towards insanity. But, it doesn't help when the winter solstice is nigh and the lab is completely empty. With humanity back, spring approaching, and the RNAses at bay (at least for now), I think the worst is over.

In other news, Steve Chu's confirmation hearing was today, and in spite of some unfortunately honest comments about coal that he made back before he was supposed to be playing politics, it sounds like he's going to sail through. (I believe, at my suggestion, he was awarded the "Lamest Excuse for Not Showing Up" award at the Aspen meeting, since he was originally supposed to attend but then cancelled.) It will be nice having an actual scientist in charge over there, but I think the political rhetoric is a bit much. I think cold atom trapping is great and all, but “One of the great, brilliant thinkers of his generation," as Dianne Feinstein put it, is kind of over the top. I will happily entertain comments from those who disagree though.

Twas the Fourth Night of Channukah, and All Through The Lab...

2008-12-24T09:51:00.001-08:00

...not a creature was stirring, etc. Just wanted to give a shout out to the Members of my Tribe, bravely holding down the fort while everyone else enjoys their ham and figgy pudding. All the equipment is available, and I have Mr. Ipod to keep me company! And, if you're in the bay area and are bored tonight, swing by the Latke Ball, that's where I'll be!

(h/t to The Poorman Institute for the video!)

Thoughts from a Biophysicist on Attending the American Society for Cell Biology Conference

2008-12-18T13:08:00.000-08:00

I always approach meetings with a combination of excitement and dread. My inner-child-scientist is always excited; new science! New people! Interesting talks! Gadgets! Data! Fun!

On the other hand, I've been to enough conferences to know that, in reality, I tend to spend a lot of time bored. I don't have a great attention span in general, and I have a very low tolerance for bad talks. And, as Sturgeon's Law tells us, 90% of all talks are bad talks. So, conferences require a great deal of mental energy to stay alert, awake, and engaged. And don't even get me started on posters; trying to absorb scientific data from a 4' by 3' board covered with 12 point type while surrounded by hundreds of jabbering people is close to impossible for me.

That being said, I always come away with something, a few kernels, and its these things that make it all worthwhile. Plus, the science is really only half of the reason to go to a conference; the other half is the networking: seeing old friends and colleagues, gossiping, finding out who's hiring whom, and ingratiating yourself with your betters. And, that's really the fun part, since that part usually involves beer.

In the past, I've been to the Biophysical Society Meeting, but since ASCB was in San Francisco this year, and I had some money from my F32 grant to cover the registration costs, I thought I'd give it a shot and see what it was like.

One thing that struck me is that there are several different ways that you can break down the participants into groups, and the meeting seemed to use each of these at different times: by technique, by disease, or by molecule of interest, for instance. Biophyscists tend to be very technology/technique oriented, so I attended several technique-oriented sessions, on single-molecule techniques, and imaging and biosensors. Unfortunately, the single-molecule material being presented at ASCB was not, by and large, ground-breaking work, from a technique standpoint. It was mostly the usual suspects: centroid tracking of molecular motors, microtubule studies, and optical trapping of polymerases were all covered. It seemed disjointed, I think, because the ASCB is such a biology-oriented meeting, and having technique talks lumped together without regard for the biology didn't seem to be in the spirit, in some ways.

On the other hand, there was a lot of good stuff at the biosensors and imaging sessions. The Hahn lab at UNC has developed a genetically encodable photoactivatable protein, which could, in theory, do for photoactivatable proteins what GFP has done for fluorescence microscopy. The Smith lab at Stanford had some amazing mouse brain images at the single neuron level developed with a new technique they call "array tomography", which involves physical sectioning of the tissue into ultrathin slices prior to imaging. There were also numerous talks on new photoactivatable proteins for use with PALM, although few actual applications.

I also got to see some friends who I haven't seen in a while. Arne Gennerich was there, who is flying between UCSF and Albert Einstein, in the process of setting up a new lab there. We talked about hang gliding, motorcycling, hot dogs, and shoes. And some science. Josh Shaevitz was also there giving a talk, allowing me a glimpse into the origins of the crap hat.

Betsy Villa, a friend from grad school, was there, on her way from Munich to Mexico for xmas. One of the things we talked about was the difficulty for a biophysicist of figuring out what's really novel, and what's just run-of-the-mill at a cell biology conference. For instance, on the last day, I spent most of the day at talks on non-coding RNA, which included a lot of material on microRNA. There were a lot of people doing screening assays to figure out which microRNAs affected which tissues, and in what ways, but there was very little discussion of what the mechanistic details were; the emphasis was more bio-informatical (if that's a word), trying to establish simply links between particular miRNAs and particular genes. After watching several of these talks, it all started to blend together for me. Was this really the state of the art? Or was this simply something that you could do that would be low-risk and produce lots of papers, something to help you keep your grant and get tenure? I wasn't sure.

One thing I was sure of was that almost none of this material would have been comprehensible if we hadn't gotten as far as we did into our Fat Alberts Club at lab. I'm very grateful that we stuck it out as long as we did, even if we didn't get to the end of the book.

I may add some other thoughts as they occur to me, but that should give you the basic flavor, and I have to go finish cleaning up my labeling reaction stat.

Off to see the wizard

2008-12-13T10:05:00.001-08:00

Catching the train to head up to ASCB! See you there!

Microscopes for Fluorimeters: The Era of Single Molecule Measurements

2008-12-11T11:28:00.000-08:00

Just in time for the ASCB meeting this weekend, Ron Vale has a review article in Cell titled Microscopes for Fluorimeters: The Era of Single Molecule Measurements (samizdat copy on the Vale lab web site here.) In it, he points out the fascinating tidbit that the typical forces observed in force spectroscopy measurements (~5 pN) are actually several orders of magnitude less than the gravitational attraction between you and the journal you're reading (assuming that your'e reading it in hardcopy, in journal form, which is almost certainly not correct. But still.)

I'll be at ASCB this weekend, and I will not be liveblogging, but I will do a post-meeting roundup on some of the stuff. One thing to make sure to attend will be the subgroup meeting on Saturday, At the Limits: Optical Methods for Single Molecules, Cells, and Organisms, from 12:30 to 5. Ron Vale will be speaking there, along with lots of other fun people.

Steve Chu Named Secretary of Energy by Obama

2008-12-10T15:32:00.000-08:00

Steven Chu, Nobel Laureate, single molecule biophysics pioneer, and current director of LBNL, has just been named Secretary of Energy for the Obama administration. How awesome is it that we have an incoming president who actually wants to put a Ph.D. and Nobel Laureate in charge of energy? Compare that with the Bush appointment: a political hack (and founder of the Federalist Society) who perpetrated the Hydrogen Hoax.

Apropos of nothing, a brief personal story about Steve Chu: For the UIUC Physical Revue one year, I wrote and sang "I Am The Very Model of a 'Sperimental Physicist" (preserved for posterity by the Internet Wayback Machine.) In it, I sang:

"I've got so many articles, my Erdős number's less than two/I'm published more than Rutherford, Yukawa, Gauss, or Steven Chu!"

I wrote it that way because the meter worked and it was funny. But, apparently, TJ Ha, who postdoc'd with Steve Chu (and with whom I co-authored a paper) was talking with him at BPS that year, and mentioned the song, which elicited the reply, "That's odd, I don't publish that many papers." Well, at least he's not getting tapped for Secretary of Humor.

Single Dancecules

2008-12-05T10:26:00.000-08:00

I did my doctoral work at UIUC, and it is traditional there for physics grad students there to try to meet actual real women by going to dance classes. Salsa was the usual choice, but I would frequently see signs up in the physics department for Argentine tango. So, the following comes as no surprise to me: Via Greg Laden over at Scienceblogs.com, we find the following video of Markita Landry from Yann Chemla's group at UIUC, doing an interpretive dance of her thesis, titled "Single Molecule Measurements of Protelomerase TelK-DNA Complexes":

Real-Time DNA Sequencing from Single Polymerase Molecules

2008-11-25T16:53:00.001-08:00

Just coming down the line now is this paper in Science on single molecule sequencing using fluorescent bases incorporated by DNA polymerase. Besides the huge "Wow!" factor, this paper comes out of Pacific Biosciences in Menlo Park, featuring two Block lab alumni, Adrian Fehr and Ravi Dalal. In addition, I just noticed that the first first-author (as opposed to the six other first authors) is none other than John Eid, one of my contemporaries at U of I, who worked with Enrico Gratton in the Laboratory for Fluorescence Dynamics (now at UC Irvine).

Hola Amigos

2008-11-25T11:08:00.000-08:00

I know it's been a while since I rapped at ya, but I wanted to just point out a couple of interesting recent papers.

Elio Abbondanzieri has struck again, this time with a paper in Science, about shuttling of HIV RT. I havent' read the paper closely, but the title is reminiscent of the Ha lab work on Rep helicase, in which they also used smFRET to demonstrate shuttling along short oligos.
I spied this paper sitting on a colleague's desk, and perused it briefly. Another entry in my fetish for single molecule 3D tracking techniques.

Also, apropos of nothing, I thought I'd just point out my new blog, 82 Eateries. This is a solution to the age-old problem of "where to eat?" When we don't know where to go, we start driving on El Camino, and stop at the first place we find that we haven't been to yet. Then we write it up. It's an experiment in gastronomic geography, if you will.

Postdoc position available in the Muller Lab

2008-11-14T11:17:00.000-08:00

Hagar Zohar from the Muller lab at Berkeley contacted me and asked me to post an opening for a postdoc in their lab. We here at In Singulo aim to please! Details:

Post-doctoral Position Available: Biochemical synthesis of DNA binding proteins

for single molecule studies

A post-doctoral position is available in the area of single molecule detection of specific DNA-protein complexes using fluorescence microscopy. Protein probes are designed to bind sequence-specifically to target nucleic acid sequences; the ultimate goal is to engineer a microfluidic genotyping tool. Qualified candidates will have expertise in biochemistry and molecular biology including recombinant DNA technology, protein purification, DNA-protein interactions, nucleic acid enzymology, PCR, and related methods. Previous experience in single molecule studies is preferred, though not critical for the position. The primary initial focus will be protein probe design and synthesis; this work will be coupled to on-going efforts on single molecule studies in microfluidic devices. This project is part of a larger collaboration with the Shaqfeh group at Stanford.

This position is available immediately, and will remain open until filled. The initial appointment will be one year; renewal will be subject to mutual agreement and the availability of funds.

Interested candidates should send a letter of application, resume, and the names and contact information of three references to: Professor Susan Muller, Department of Chemical Engineering, University of California, Berkeley, 94720-1462 or via e-mail (preferred) to muller2[at]berkeley[dot]edu.

People Who Have Too Much Time On Their Hands, Election 2008 Edition

2008-11-12T15:49:00.000-08:00

Nanobama.

Stone Cold Cruzin'

2008-11-07T10:51:00.000-08:00

I have just been advised that Michael Stone has moved back to the bay area (broadly speaking), and is now on the faculty at Santa Cruz. Right down the road!

A Plethora, Nay, Dare I Say, A Veritable Cornucopia

2008-10-27T11:16:00.000-07:00

Holy jeebus, I finally got around to looking at what Pubmed sent me for "What's new for 'Single Molecule'" last week, and there is too much there to even begin to consider reading. Rather than try to read all of this and summarize, I just want to point out what look like some highlights based on the abstracts. When I get a chance to read some of this later on, I'll try to fill in the details:

Force spectroscopy

Theory, analysis, and interpretation of single-molecule force spectroscopy experiments: Olga Dudko's group updates their highly important theoretical work on interpreting non-equilibrium single molecule folding and unfolding experiments with this new paper. From people who read the pre-print, I understand the functions they give in this paper give much more robust fits than the ones in their previous work.
Length of Time's Arrow: Gavin Crooks (of the Crooks Fluctuation Theorem fame) has a paper in Phys Rev Lett which uses the reversible folding and unfolding of RNA molecules to investigate fundamental questions of why time runs in one direction. That is some seriously hardcore physics, and one of the rare few examples of "biology in the service of physics" rather than "physics in the service of biology." I hope I haven't forgotten too much stat mech to make heads or tails of this, but I'm going to give it my best.
Remeasuring the Double Helix: While not strictly about force spectroscopy (nor actually single molecule, for that matter), this paper from a group here at Stanford uses small angle X-ray scattering (SAXS) to investigate the bending behavior of small DNA molecules, a very hot topic. This relates to single molecule force spectroscopy because some experiments show the apparent behavior of short molecules differing markedly from the behavior seen in single molecule pulling experiments of longer molecules. This work supports the view of Jon Widom's work (among others) showing much higher flexibility than expected for short double stranded DNAs.

Fluorescence

Single-molecule spectroscopy of fluorescent proteins: ~~Vijay~~ Vinod Subramaniam is an expert on photophysics of fluorescent protein, and as these proteins are getting used more and more for single molecule assays, their photophysics in the single molecule regime are more important. This looks interesting.
A stochastic single-molecule event triggers phenotype switching of a bacterial cell: I haven't been following Sunney Xie's work very closely, but they have been working on single molecule detection of gene regulation, and this new work continues along that direction. Probably worth a look-see.

UPDATE: A reader corrected me on Vinod Subramaniam's first name; I was thinking of the late great Vijay Pandharipande, from whom I took QM in grad school.

Article Title of the Day

2008-10-21T14:57:00.000-07:00

Tentacle probe sandwich assay in porous polymer monolith improves specificity, sensitivity and kinetics.

Mmm...tentacle probe sandwich...

Friday Cat Blogging!

2008-10-17T14:15:00.001-07:00

Just because I can.

New advances in single molecule NMR

2008-10-13T10:08:00.000-07:00

A while back, I blogged about some experiments back in 2004 demonstrating detection of single spins. Now, two back to back * papers in Nature have utilized a new method for detecting single spins at room temperature. Nature also has a News and Views that discusses both papers. Both techniques utilize long spin coherence states of diamond nanocrystals with single defects, which sense changes in spin tens to hundreds of nanometers away, and can be detected optically. Optical detection is a highly desirable mechanism because of the highly developed technologies allowing reliable, low-noise detection of single photons. And, the ability to image spins at room temperature offers hope that these techniques could be used for biological studies.

*Belly to belly!

A Nobel Prize for Acronyms

2008-10-08T12:24:00.000-07:00

Roger Tsien won the Nobel prize in Chemistry today for his work on GFP, a resounding affirmation of the role that goofy acronyms play in biophysics. The Tsien lab gave us such memorable names as "Fluorescein arsenical helix binder" (FlAsH), "resorufin arsencial helix binder" (ReAsH), and its brominated cousin (BrAsH). I seem to recall being told, back when my advisor was doing a sabbatical in their lab, that they were working on a fluorescein-based histidine binding dye which they were calling "hissy fit", but I can't seem to find any evidence of that in the literature. In any case, congratulations, and here's to a future filled with puns!

From the Cold to the Old

2008-10-03T10:32:00.000-07:00

Via the CM/AMO rumor mill, Phillipe Cluzel has moved from U Chicago to Harvard. The Cluzel lab has done work on in vivo mRNA quantification (a hot topic in a lot of labs), as well as trying to understand the dynamics of the network that controls bacterial chemotaxis. I interviewed for a postdoc with the Cluzel lab before winding up here at Stanford, and I have to say I'm pretty glad that I wind up working there so that I could arrive just prior to a lab move; there's no better way to lose six months of research time than to have totear down a lab, move it 1000 miles, and set it up in a new place. That aside however, congrats to the Cluzel lab, and good luck at Harvard (or as Tommy Angelini, a friend and postdoc there likes to call it, "Tardvard.")

I ♥ γ's

2008-09-22T16:13:00.000-07:00

I'm a sucker for new ways to get more photons out of your sample, so this one struck me as pretty neat. Metal-enhanced fluorescence has some huge advantages, and this looks like a great way to improve your fluorescence yield a lot without having to change your assay around too much: just deposit a monolayer of silver nanoparticles on the coverslip surface, and presto! Instant gratification. It doesn't sound like a huge chore to make the coverslips, although it's not a walk in the park either. But hopefully somebody will start selling something like this soon, and you can just buy it off the shelf.

The Mighty Myosin

2008-09-10T21:14:00.000-07:00

Takeshi Sakamoto (warning, absurdly large image of Takeshi on this web page) from Jim Sellers' lab has a paper in Nature this week on myosin Va. (Takeshi hung out at the Selvin lab a few times and he's a nice guy.) By using a fluorescent ATP (deac-aminoATP) analog that increases its fluorescence 25-fold when docked into the myosin, they were able to visualize ATP and ADP binding and unbinding from the myosin, while simultaneously visualizing stepwise by localizing the flurophores, thus allowing them to determine at what point in the mechanochemical cycle the ATP binds and the ATP unbinds. This is a big problem for a lot of motor molecule researchers, so hopefully this will be a new technique in the arsenal.

Speaking of myosin V, it is apparently now official that Ahmet Yildiz has started a position at Berkeley in the physics department. Congrats!

Gordon Conference

2008-08-26T11:34:00.000-07:00

The 2008 Gordon conference on Single Molecule Approaches to Biology took place last week, and we got a full rundown from Steve on the proceedings. All of the big names came and talked up a storm, including an entire session on super-resolution imaging (one of my hobby horses), featuring Xiaowei Zhuang and Stefan Hell, among others. TJ Ha chaired a session on transcription and translation, and has apparently started looking at T7 RNA polymerase, and is able to see something akin to scrunching using smFRET.

Dude, your physics is showing!

2008-08-01T15:04:00.000-07:00

As a biophysicist, I long ago gave up on trying to figure out if what I was doing was considered actual-real-honest-to-goodness physics by other physicists. I figured I would work on what interested me, and if other people thought it wasn't real physics, well, that was just a dick measuring contest that I wasn't going to get into. That being said, there are still some things that warm the cockles of my heart occasionally (or perhaps, as Dennis Leary would say, somewhere in the sub-cockle region). A couple that crossed my browser today:
Via McSweeney's, Physical Theories as Women. e.g.:

Quantum mechanics is the girl you meet at the poetry reading. Everyone thinks she's really interesting and people you don't know are obsessed about her. You go out. It turns out that she's pretty complicated and has some issues. Later, after you've broken up, you wonder if her aura of mystery is actually just confusion.

Jesus. I think I've dated a lot of wave functions by this criterion.

The second is this rap video about the LHC (avid readers of this blog will probably have noticed that I can't resist posting videos, especially musical ones about science) It's pretty good:

Sometimes, I do miss it...but then I remember that all my condensed matter friends are now working on Wall St.

Michelle Wang named HHMI Scholar

2008-07-22T15:19:00.000-07:00

Michelle Wang, a former Block-lab postdoc and optical trapping aficionado, has been named an HHMI scholar. The Wang lab works very much along the same lines as the Block lab, using optical trapping to study DNA interactions with various proteins, as well as fundamental DNA properties. They also have published some interesting work on an optical torque wrench, an instrument for applying and measuring torques to optically anisotropic particles using polarized light, in a manner similar to the way magnetic tweezers can be used with paramagnetic particles.

Also, the word coming down the grapevine is that Ahmet Yildiz has accepted a faculty position at Berkeley, though it does not appear to have been officially announced yet...more on this breaking news as it arrives!

Single atom imaging by TEM

2008-07-21T16:24:00.000-07:00

From the cover of this week's issue of Nature, Meyer, et al show that TEM can be used to image individual atoms and molecules with high resolution if it is done against a graphene background. The video above is from the supplementary material, showing a single carbon chain suspended between two pieces of junk. It's a bit amusing that some of their most interesting data, showing carbon chains and polymers, is basically due to "vacuum contaimation", aka, crap in the chamber. But, it's interesting nonetheless. Admittedly, this has little to do with biology, and is unlikely to be very useful for biology because of the need to do it in vacuum. But it could be used to study fundamental polymer dynamics in interesting ways. Anyway, I just thought it was cool and worth mentioning.

New Directions in Biology-Based Music Videos

2008-07-12T10:42:00.000-07:00

First, there was The PCR Song, in the We-Are-The-World style. Then UMass innovated in the rap genre with This Is How We Do It. Now, Eppendorf breaks fresh ground with their boy-band themed (and frankly a bit creepy) [It's Called] epMotion:

I'm not sure this is a good trend. I'm waiting for the death metal FRET videos to start appearing.

By the way, am I the only one who had a momentary internal freakout when you see the guy throw the pipetter? "OH MY GOD, THE CALIBRATION WILL BE ALL OFF! THE HUMANITY!!!!"

[Hat tip to Peter Anthony for pointing this out, on a Friday night at midnight, no less.]

Imaging HIV assembly in real time

2008-07-10T14:32:00.000-07:00

A movie from a new paper, Imaging the biogenesis of individual HIV-1 virions in live cells: A video of fluorescent GFP-Gag, an HIV structural protein, assembling into individual virus particles. The actual assembly happens over about 40 minutes.

Nobel symposium

2008-06-17T10:59:00.000-07:00

Steve just returned from the Nobel symposium on "Single Molecule Spectroscopy in Chemistry, Physics, and Biology" held in Stockholm. Unfortunately, there's almost no information online about it, but a lot of the major US players were there, and it was jam packed with talks. I am also told that a number of talks discussed the history of high-resolution imaging, and that I was cited by one researcher as "M. Gordo". That was, of course, back in grad school, when I was 25 pounds heavier.