Biophysical Society Newsletter
3
JANUARY
2014
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,
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
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 (
),
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.”
Gnana with his wife Brintha, daughter Neytra, and
son Navin.
