Biophysical Newsletter - January 2014

3

Biophysical Society Newsletter

2014

JANUARY

genetic, and cellular pro- cesses in order to understand how multi-drug resistance efflux pumps are able to resist so many antibiotics. Gnana’s group has also been instrumental in establishing theoretical capabilities to overcome challenges related to cost-effective biofuels. “Biophysical questions concerning the enzymatic degradation of cellulose are what really got me started

putational approaches can be used to solve chal- lenging biophysical problems,” Gnana explains. After completing his postdoc with Garcia, Gnana stayed on in the theoretical biology and biophysics group at LANL as a staff scientist. One of the great benefits of working at LANL has been the close proximity of talented researchers in a variety of fields. “As I have started studying more biophysi- cal problems,” Gnana says, “I realize that no single approach is enough to solve a problem, and many different approaches need to be implemented together.” With access to this impressive pool of researchers, an interdisciplinary approach has become an important feature of his current research program. One of his frequent collabora- tors at LANL is Byron Goldstein . The pair has recently worked together to build detailed models of cell signaling cascades. These models can be problematic because they contain a large number of parameters that need to be evaluated in order for the models to have predictive value. Goldstein explains, “Gnana and I have collaborated to try to bring structural biology to bear on these models. A first goal of ours is to improve the estimates of equilibrium and rate constants that characterize intramolecular reactions and intramolecular inter- actions that occur on surfaces, parameters that are difficult to determine experimentally.” They have already shared some success on this project, in es- timating the intramolecular equilibrium constants frommeasured solution binding constants for the binding of the adaptor Grb2 through its two SH3 domains to the five polyproline binding sites on the nucleotide exchange factor son-of-sevenless 1. Gnana does not accept superficial explanations, demanding to get to the heart of the problem, but he does it in a gentle way.” Gnana is currently leading a project at LANL to address efflux pump mediated drug resistance – the dominant drug resistance mechanism in gram- negative bacteria. “At present, we rely heavily on antibiotics for the treatment of bacterial infections encountered in public health and bio-threat sce- narios,” he explains, “however, the rapid emergence of antibiotic resistance poses a major hurdle in the treatment of infections.” Gnana and his team are working to develop an experimentally-driven math- ematical framework that will integrate structural,

Gnana with his wife Brintha, daughter Neytra, and son Navin.

in this field,” Gnana explains, “We understand somewhat how enzymes catalyze reactions in an aqueous environment. However, in the case of cellulosic conversion of glucose to ethanol, we needed to know how three kinds of enzymes work together in synergy to break down crystalline cel- lulose to glucose.” The group at LANL has been working with the Great Lakes Bioenergy Center to find which properties determine efficient catalysis of an enzyme on native and non-native cellulose surfaces. They have also developed mathemati- cal models to identify proper mixture of these enzymes that effectively degrade cellulose. When he is not in the lab, Gnana is often still thinking about biophysics, as one of the organiz- ers of the q-bio Conference (www.q-bio.org), which he calls “a forward-looking conference on quantitative biology.” Gnana also looks forward to going home each day, where he enjoys spending time with his wife and two young children. He has even begun to share his love of sports with his daughter. Says Goldstein, “When his first child was a year old, Gnana began to watch Sunday football (American) with her on television. He introduced her to baseball as well, taking her to see the Albuquerque Isotopes play. Now three, she can talk baseball. I am sure Gnana will give his son the same broad educational experience.” For those just starting out in biophysics, Gnana has this advice, “Have a broad perspective on biophys- ics. As a biophysicist you often encounter setbacks or failures…What defines success is how one deals with failures and turns them into advances.”