Highlights from the Protein Society Symposium

A week ago, I attended the 25th annual symposium of the Protein Society in Boston.  I've gone to this meeting three times and this was the best yet.  Very, very cool stuff.  I also got to see a lot of old friends from grad school, including my graduate advisor.  It was great to hear him talk fondly about the 'good ol' days' (ie, when I was his student) as I distinctly remember them being less fond and more frantic.  I think finishing a PhD thesis is the mental equivalent of giving birth to an elephant while running a marathon, but for several obvious reasons I will never be able to test the hypothesis.  I also met some cool new people.  I talked politics with a girl from Poland in a loud Irish pub and met another girl who is some kind of flute prodigy from a well-known coffee empire.  At the reception, I met a guy from, well, some European country who had done a postdoc in San Diego and I knew many of the trails he had hiked.  We tried watching the Red Sox game from the 50th floor of the Prudential building... great view but when the outfielders look like fleas on a green dog, it's really hard to see what is happening.  We kind of made it up as we went along and since the Polish chick didn't know the game, it was all good.  He still owes me pictures of Fenway.  The poster session was crazy, with two overlapping sessions and the very friendly (but bored) vendor who bribed me with chocolate every time I passed her booth.  I was also a poster judge this year, so I missed most of that session, but tracked the presenters down later to ask questions.  It's a little awkward at the coffee breaks, since everyone is staring at the nametags trying to find people they want to talk to.  I would try and catch a glimpse of their badge over the rim of my coffee and hope they were not offended when I simply walked away.  It's a very unusual hierarchy at conferences.  There is absolutely no guessing about where you stand in the pecking order.

Anyhow, I can't talk about the things I found most exciting because I was there for work, and work stuff has to stay off the radar.  However, let me briefly describe two (not work-related) things that were pretty cool.  One was a talk by Della David at UCSF on protein aggregation as a part of aging.  I don't know a lot about this field, but one of her early slides really caught my attention.  She was discussing the role of protein "aging" in inducing aggregation using C. elegans (a worm) as a model.  As the worm aged, she showed that the concentration of over 400 different proteins increased in the insoluble fraction.  In simpler terms, if you take all of the proteins out of the worm, many of them are soluble but some fraction are in an aggregated form, which is not soluble.  Although the total amount of protein seemed fairly constant with age, the proportion of aggregated protein increased and seemed to disrupt the natural process of homeostasis.  Then came the kicker... to show that this was an active process (that is, controlled by a cellular system) she used a C. elegans that had been engineered to have a specific mutation in the Daf-2 receptor.  These worms had twice the life span of a normal worm.  Whoa!  Sign me up for that mutation! Imagine living 160 years!  It turns out that the fraction of aggregates is independent of the lifespan, suggesting that the process is controlled.  Two things here... Daf2, which is part of the insulin/IGF-1 signaling pathway, can regulate lifespan (possibly related to the observation that mice that eat less live longer?) and that protein aggregation as a result of aging could also be controlled.  Here is a review on insulin/IGF-1 signaling in aging (abstract) and here is David's recent open-access paper covering some of this story (PLOS paper).  Listen folks, please hurry up with this important work... I'm not getting any younger.

The other talk I liked was by Ken Dill (a long-time favorite of mine and also from UCSF).  I'm used to him talking about transfer free energies and lattice models for proteins but this time he was talking about the stability of the proteome.  He (and others) have shown pretty convincingly that on a macro scale, protein stability is roughly dependent on the length of the protein.  (Seems simple but it has taken decades to model it in a way that makes physical sense).  Armed with this model, he determined the stability of the entire proteome and found that it is only marginally stable.  Over 500 proteins have stabilities less than 3 kcal/mol, which means they are barely folded and functional.  The implication of this result is that even slight increases in temperature can cause many of these proteins to unfold.  The resulting denaturation catastrophe overwhelms the cell and causes cell death.  This is the most plausible explanation yet for why slight increases in temperatures cause such problems (even for humans, an increase in body temp of 7-8 degrees can be fatal).  I asked him about the proteome of thermophilic bacteria and whether it might explain their ability to survive extreme temperatures and he said he is working on that now.  I'm guessing that might explain some of the adaptability, although the detailed mechanism is still a mystery.  For you DIYbio people out there, this model provides a pretty simple way to do this type of analysis yourself. The simplicity of the model, and the fact that minor ensemble changes can be magnified into major improvements for the organism tell me that life might be lurking everywhere there is an energy gradient (I'm looking at you, Titan).  On the flip side, it shows how sensitive life can be to slight changes in the environment. Here are the links to the articles (proteome stability and Dill's model)

  Dill also started off with a joke: "There are three kinds of mathematicians... those that can count, and those that can't."  Nothing like a geek joke to start off a talk... but hopefully his material will be better in San Diego next year.