July 3, 2013

Part II: “If you love what you do, you never have to work a day in your life.” – Confucius

Dan Shechtman, delivered his lecture “Quasi-periodic materials – Crystal redefined.” He is a crystallographer, but his original adviser was not interested in Dan’s goals. So he quit and joined a new lab. Even Linus Pauling, one of the world’s most respected scientists at the time declared, “There is no such thing as quasicrystals, only quasi-scientists,” about Shechtman. Ouch.

But Shechtman observed, to his disbelief, a five-fold symmetric crystal diffraction pattern. Even in his notes he wrote a huge question mark next to the data. He persisted to test the result and found, to his amazement, that crystals do in fact diffract to an odd-numbered symmetry, and a collaborator’s lab in France, the experts in that field, confirmed the results with highly accurate data. That then led to the Nobel Prize.

Paul J. Crutzen, along with fellow 1995 Nobel Laureates Mario Molina and F. Sherwood Rowland, saved the world. That is, they discovered that nitrogen oxide, spewed by fossil fuel burning machines, depletes ozone in the atmosphere (recall that most of our atmosphere is actually nitrogen, not oxygen). Ozone serves as a molecular sink that absorbs solar radiation that would otherwise cook our planet to an uninhabitable state.

During his talk, “Atmospheric chemistry and climate in the ‘Anthroprocene’”, Paul told us about his serendipitous, unlikely path to the Nobel Prize. In fact, he says, “chemistry definitely was not one of my favorite subjects.” But he loved research, learning, and that was the invisible hand that drove him to greatness.

Kurt Wüthrich’s lecture, due to the thirty minute limit, treated G-protein coupled receptors (GPCRs) saliently. GPCRs are incredibly important for human health and are thus a huge part of drug discovery. Especially resonating with me was his introduction which discussed the importance of dynamics – not just squishiness but wiggliness – to understanding biomolecular function, because biology lives well above absolute zero temperature. That means every single molecule in a cell is wiggling about with energy proportional to the temperature; temperature is simply a measure of the average degree to which molecules wiggle freely. While x-ray crystallography is an absolutely powerful experimental tool, the utilization of which has duly led to a mountain of Nobel Prizes, its data depicts the state of a molecule at a completely not biological temperature.

Wüthrich instead uses 19F Nuclear Magnetic Resonance (NMR), which allows you to determine the structure of a molecule at biological temperature. In addition, it allows you to study the molecule in a solution rather than in a crystal, a further advantage over crystallography. However, NMR still delivers an average structure. Even if the variance is known, molecules with important but undetectably transient states may not be fully characterized.

In any case, Wüthrich lab’s NMR has delineated a detailed story of the subtle structural dynamics of GPCRs as they do their job. Like a Swiss watch, dozens of interacting components work together in a symphony of concerted motions to yield an overall functional effect – instead of the hour hand moving, a bundle of long helices shift the location of kink points. And that is how, we believe, GPCRs do their duty.

It would be tough to say I had a favorite lecture, especially in a public way. But the lecture given by Richard R. Ernst, “Widen your scope by extracurricular activities: My example,” brought tears to my eyes more than once in that thirty minute minuet, leaving a lasting impression onto my scientific soul that I cannot describe in any other way than, religious experience. It was that profound. It wasn’t just the research or the science. It was the humanity. It was the feeling of learning who he really was. Please, I beg of you, watch his lecture on the Lindau Mediatheque.

…kevin eduard hauser