Energy Independence: From Steven Chu’s Talk to Type IB Topoisomerases

I’ve always lived on a coast, or close to a body of water, so when I moved to Urbana-Champaign, Illinois 4 years ago for graduate school, I suffered (and still suffer) from severe fresh seafood withdrawal. Not to say that East-Central Illinois doesn’t have any seafood, but I am always a bit hesitant to eat seafood in a landlocked city. Baltimore has provided me with a seemingly bottomless supply of my favorite foods such as fresh sashimi at Edo Sushi last night with a handful of other BPS students. Today I cooked some crab cakes and salmon-crab rolls for dinner in the kitchen of the fantastic HI-Baltimore youth hostel in which I am staying. Delicious!

For most BPS attendees, the highlight of the conference occurred this afternoon, as the 12th U.S. Secretary of Energy Steven Chu addressed a standing-room audience with his talk: Biophysics in a New Light. Chu covered more topics than normally feasible in a one-hour timeslot. First, Chu spoke about emerging techniques in super-resolution. “Can we do better than sub-nanometer resolution? To quote my boss [President Obama], ‘Yes we can!’”. Furthermore, unlike STORM or PALM imaging techniques which require a stationary sample, the super-resolution imaging technique described by Chu can be applied to a moving sample. Chu concluded with a brief overview of the energy crisis, referencing the rising price of oil per barrel, and provided the audience with a few suggestions for how to combat the energy problem through the role of 1) biophysicists and 2) citizens who will inevitably be affected by this crisis. Chu claims that engineering batteries with better energy densities will provide a fundamental technology with which to build better and more energy (and cost) efficient hybrid and electric cars. Chu also mentioned that biofuels are another area of research with tremendous potential for the substitution of our currently near-depleted sources of energy. Systems or synthetic biologists and scientists who study directed evolution are in a good position to contribute to this area of research. Chu ended with a comment about the importance of basic (or, curiosity-driven) research, which received a burst of applause from the audience. Like the audience, I was elated to hear this opinion from a prominent politician, as I have always believed that the world would be a better place if more scientists went into politics, and fewer politicians went into science.

This afternoon’s poster sessions were great. Realize, that when I highlight talks and posters here, I will inevitably be biased by my personal interests and my own research endeavors. My two main projects include 1) a single-molecule study of Topoisomerase IB, TelK, interactions with DNA as studied with high-resolution optical traps, and 2) DNA-wrapped nanotubes for the development of a label-free live-cell imaging platform.

I came across some great work being done by graduate student Sanghua Lee from Sungchul Hohng’s lab at Seoul National University. This poster explained a study of DNA bending induced DNATopoisomerase II alpha. Type II topoisomerase enzymes are involved in the regulation of DNA topology, which, unlike type I topoisomerases, require ATP hydrolysis for their function. Lee’s study showed that DNA bending is sequence-specific, and marks a pre- DNA cleavage step at the topoisomerase DNA target site. I found this work to be particularly interesting because (again: bias warning) I think topoisomerases are amazing little protein machines. Type I topos perform many of the same energy-expensive functions (DNA rearrangement or cleavage) but don’t use any ATP. I’ve dedicated much of my graduate work to explaining how topo IBs manage to perform difficult and energy-expensive functions without high-energy cofactors. Lee’s work suggests that pre-cleavage DNA bending might be a source of this energy, further emphasizing a mechanism that I personally believe to be responsible for topoisomerase function: topology-regulated and topology-driven catalysis.

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