A piece published yesterday on the Scientific American blog network's Curious Wavefunction offers a closer look at the work of Nobel Prize winner Brian Kobilka, MD. In the post, writer Ashutosh Jogalekar calls Kobilka a "tour de force of science" and details how he overcame various challenges during the course of 20 years before winning the Nobel Prize:
Just like in mountain climbing both perseverance and luck play a crucial role in attaining your goals when it comes to protein crystallization. In case of Kobilka the perseverance was there since the beginning, from the time that he started as a postdoc in his fellow Nobel Laureate Robert Lefkowitz’s lab at Duke. It took a little more time to get lucky. Crystallizing proteins and especially membrane proteins is as much of an art as a science, and much depends on employing countless rounds of trial and error to find the right combination of conditions that would coax crystals to assemble in an orderly periodic lattice. Kobilka’s early years were spent trying to find antibodies that would stabilize the especially jittery parts of the beta-adrenergic receptor, a workhorse of GPCR structure and function that is both the target of numerous important drugs for hypertension and a “model organism” for other GPCRs. Indeed, it is largely Kobilka’s work that has turned the beta-adrenergic receptor into a microcosm of all that is good and interesting about GPCRs. In zeroing in on a specific example whose details provide insights into the general problem, Kobilka is following in the footsteps of distinguished scientists like Max Perutz (hemoglobin), Hartmut Michel (photosynthetic reaction center) and Roderick McKinnon (potassium ion channel) who have also used a single instance of a protein to shed light on more general features of a family.
After years of trying antibodies from several different organisms to try and stabilize his chosen protein, it was a chance encounter with a fellow researcher at a Gordon Research Conference that gave Kobilka the idea of using llama antibodies to lock on to the receptor and rigidify it. Kobilka got lucky, but his mind was primed to recognize the lucky moment through years of patient and dogged pursuit.
Previously: Video of Brian Kobilka’s Nobel lecture, Going behind-the-scenes at Nobel Laureate Brian Kobilka’s press conference, Memorable moments from Brian Kobilka’s Nobel win captured on Storify, Image of the Week: Nobel Laureate Brian Kobilka celebrates with colleagues and friends, A busy morning for Nobel Laureate Brian Kobilka and Stanford’s Brian Kobilka wins 2012 Nobel Prize in Chemistry
Photo by Linda A. Cicero