Saturday, May 12, 2012

Trifling Observations

The major issue with working at interfaces is that when you need to return to a place of stability, said place of stability often needs quite a bit of attention. You've left it abandoned and unattended, and it will suck up all of your effort until you've returned it to a state of steady reliability. Of course, one never lingers for long, as there either is a new avenue to wander down in one's research or to bring a different project off the back burner.

This tangentially ties into some discussion last month (at a couple of blogs, by my recollection) about how the academic sector does not adequately prepare one for positions in the private sector, at least insofar in chemistry. While numerous wry remarks can be made about the state of the chemistry job market in response to this, it relates - broadly - to the breadth of modern chemistry. Even if you were to organize a curriculum solely for aspiring chemists (here in the US, aspiring engineers and biologists & medical students make up a non-trivial fraction of the general and organic chemistry student populace), you still have to figure out how to make a course palatable for those who may end up working in any number of fields and subspecialties, and will likely end up switching and moving about in any case. The idea (naive as it might be) is that one develops the foundation to pursue anything from synthetic organic chemistry to ultrafast chemical dynamics to chemical biology. Or even all three, if you're feeling adventurous.

Anyway. Read more!

Monday, May 7, 2012

Cultural Differences

There was an interesting post over at In The Pipeline last week about the differences between chemists and biologists, in particular the nature of how chemists and biologists conduct research presentations in mixed company. As the vast majority of my experience is in academic environments, I will not claim that any of the following observations necessarily extends beyond the weed-ridden walls of academe.

1.) Biochemists do aspire to make details of individual preparations something that can be avoided. Certainly, for those of us who are not working with wretchedly ill-behaved proteins (at least on occasion), we can basically just describe the protocol in broad terms (overexpression, cell lysis, clarifying the lysate, and the chromatographic methods/other procedures). I've done that without specifying buffer compositions in exacting detail before. Also, we are trying to make things as routine and unexciting as possible - preparing protein constructs with cleavable affinity tags; expressing eukaryotic in bacterial cell strains that compensate in various ways for not having all of the innate eukaryotic metabolic machinery; using multi-well plates for spectrophotometric assays of various sorts. We would like for things to be boringly reliable, rest assured.

2.) One fundamental problem with presenting material to mixed audiences is that your own people are in attendance waiting to pick your stuff apart. Not necessarily in a malicious manner, of course - well, at least not always. In short, you might decide to go light on the detailed mechanistic enzymology (say, for sake of example, you are an enzymologist) in your latest talk, but what then happens in the Q&A session? Your fellow enzymologists pepper you with a dozen intricate mechanistically oriented questions in no time at all. Six months later, you present again in front of this mixed audience. You have included adequate enzymological detail in your talk and slides. The cell biologists and analytical chemists yawn, and the synthetic chemists wonder why you're boring them with this information. And now you'll never break the chain.

3.) Biology fundamentally means working with living organisms. I sometimes have the impression that chemists who haven't ever done any substantive biochemistry or biology research don't fully appreciate this distinction in the visceral way that those of us who have fallen to the Dark Side do. If it takes a week for something to grow up, then that is what we do. We can't just toss it on a hot plate to speed things up. Conversely, not everything can be stashed in a freezer to wait until tomorrow (although when it can, we do appreciate it). There's also the price of doing interesting biology/biochemistry, where the efforts to make things boringly reliable in point 1 are nowhere near being implemented.

There's certainly more I could eventually think of, but these were the major points I wished to mention. I, personally, do my level best to make my points as understandable and transparent as possible when giving a talk. Of course, given that some of my ideas involve slaughter by spin Hamiltonian, it can be easier said than done...... Read more!

Sunday, April 29, 2012

Sunday Contemplations

It's been a lively time on the chemical interwebs.

The entire chiral space dinosaur story is kind of getting tedious at this point. While the allegations of plagiarism certainly needs to be investigated, adjudicated, and resolved, I was most intrigued by the post here at the Curious Wavefunction. I find it convenient that he brings up the famed geologist Charles Lyell - there is a personally beloved example of what might be termed geological/geochemical contingency that I perpetually bring up at these moments.

Xanthine oxidase. You may or may not remember this enzyme from undergraduate biochemistry (well, for those of you took such a class). I mention it since it is a fairly well-known example of an enzyme which uses molybdenum as a cofactor. There are a number of molybdenum-utilizing enzymes that organisms use. However, it has been observed that certain organisms prefer to use tungsten. These are usually so-called "extremophiles" (deep-sea hydrothermal vents, in particular), where tungsten is more abundant than molybdenum, as well as needing to do chemistry at higher temperatures and under far more anoxic conditions. Perhaps it is not as dramatic as the sorts of substitutions that have been bandied about by some (hello, #arseniclife!), I will admit. But it bears consideration - how might multiple perturbations along these lines shape and remodel biochemistry?

(For anyone who wants more info on the above, I'd suggest first checking out the work of Michael Adams at the University of Georgia. If you are just curious about a point I bring up, let me know so I can reference you properly.)

The other interesting point that was brought up, IMO, was the idea of convergent evolution. This relates broadly to the idea that there are going to be certain physical "boundary conditions" one has to consider. My latest book of interest on this is Living at Micro Scale - the Unexpected Physics of Being Small by David Dusenbery. Here, the focus is on microorganisms and - to recall Edward Purcell - life at low Reynolds numbers.

I don't have anything interesting to note about DHFR since I neither deal with drug discovery nor with the biochemistry of DHFRs. Although I wonder - what if that paper hadn't shown up in J. Med. Chem.? What if it had ended up in a more general-audience biochemistry journal? Would there have been the same response? Would anyone have even noticed it on the chemistry blogosphere? I wonder.

Anyway, I'm going to contemplate lipid bilayers, detergents, and how they are clearly conspiring to make my life difficult. Read more!

Tuesday, April 24, 2012

Something to read.....

Check it out -  a recent article by Nobel laureate Steve Weinberg on the problems facing big science.  It might be noted that the article is very US-oriented, which is only fair as Prof. Weinberg is here in the US.  Still, something that we all should read.

Try to think of the major scientific efforts that have been started or completed in the last 10 years here in the US.  OK, there is that entire NSLS-II project presently going on at Brookhaven which is supposed to run not quite a full $1 billion dollars.  OK, there was also the LCLS at SLAC (the free electron laser which came online a few years ago).  Well, just so no one accuses me of a totally horrible memory, the SNS at Oak Ridge was just shy of $1.4 billion and started up a couple of years back (and they're still building the full complement of instruments to go with the source). 

Hmm.  Maybe we're not neglecting "big science" after all.   If anyone has thoughts as to how to resolve this conundrum, they would be welcomed! Read more!

Friday, April 20, 2012

Quantum Chemistry on the Cheap.

I am not liking this new Blogger interface.  I suppose it will become more familiar with time, which I might take as a reason to post more.  In any case.....

The main reason for this post is to alert those who haven't heard/seen - the January 2012 issue of Chemical Reviews is the free sample issue available to non-subscribers, and contains the (near) latest in quantum chemistry.  I know there's a tiny bit of interest in what can actually be done with these methods by some, and - at least from my POV - yet another delightful article from Pekka Pyykkö, whose material I always find interesting and readable. 

Anyway, the rest of the month, I will be mired in tremendous experimental effort.  Not going off the grid, but more "locked in an NMR room until I finally keel over in exhaustion."  Wish me luck. Read more!

Saturday, March 24, 2012

Lit Post.

A few interesting-looking papers that I have stumbled across lately:

- Cellular solid-state nuclear magnetic resonance spectroscopy. Clearly, analyzing membrane proteins that are still in the native intact cell membrane is what we'd all like to see.

- Red wine, iron telluride, and superconductivity. Sadly, I do not think that soaking any of my biological samples in a preferred alcoholic beverage will facilitate noteworthy results. Although perhaps I should try, just in case.....

- The Next Big(ger) Thing. Actually not a research article, it's a news item on mesoscale science.

As I've had to suppress a fair amount of sarcasm while writing this post, I will end things here. Read more!

Thursday, March 8, 2012

Break On Through To the Other Side

I was reminded to share this page in light of some recent conversations elsewhere. I would also encourage interested readers to check out the rest of Prof. Sethna's web site - there's a whole lot of great material on numerous interesting topics in physics and "complex systems," as well as what seems to be a nice, modern introduction to statistical mechanics for a wider audience than for whom most texts are intended. (I've only skimmed over it here and there so far - your mileage may vary.) Disclaimer - I am not affiliated with the lab. In fact, my only affiliation with Cornell is that I once dated a girl who lived in Ithaca, and her father worked at the university. Heh.

I will say that many physicists I've known - at least publicly - aren't convinced that they are after finding 3 laws to explain 99% of the behavior in the known universe. Most have far less ambitious goals (like being able to explain superconductivity for non-BCS systems), although I suppose this is their PR problem - they clearly need more Philip Andersons and Robert Laughlins to champion what most physicists are actually interested in, and not just what the very prolific high energy theorists and astrophysicists are putting on the book shelves. Of course, it's not to say that there can't be some excellent synergy going on - there's plenty of fundamental physics going on at neutron sources worldwide, and many groups are interested in using the tools of AMO physics as increasingly powerful probes of fundamental physics.

We can all recount anecdotes from our personal experiences - I met a bio grad student who clearly thought of their project in terms of cartoon diagrams without a number or semi-quantitative thought in mind, the theoretical physicist who thought that explaining his ideas to the experimentalists (or anyone who wasn't actually a frustrated mathematician) was the role of the phenomenology folks, and the chemists who complain about lack of rigor yet still seem desperate to explain everything in terms a first-year chemistry student would recognize. What we should focus on is trying to understand what is useful in such diverse approaches and work from there.

Biophysical chemists such as myself do not suffer from such faults, as we have all of their strengths and none of their weaknesses. We're also very modest. :) Read more!