Aravind Penmatsa - Molecular Biophysics Unit
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Aravind Penmatsa - Molecular Biophysics Unit
Penmatsa Lab Aravind Penmatsa, PhD Asst. Professor & Ramanujam fellow Molecular Biophysics Unit Indian Institute of Science Bangalore 560012, India. e.mail. [email protected] phone. +91-80-2293 3453 Research. I am setting up a new lab at MBU (05/2015) with an interest to carry out structural studies on membrane proteins, both to understand their mechanism and study their pharmacology. The membrane bilayer segregates the extracellular from the intra-cellular constituents. However, this protective layer has to be overcome for nutrients, ions, drugs and a range of metabolites and metabolic end products to traverse, for cells to survive and respond to environmental cues. Membrane proteins such as transporters and channels carry out this indispensable role of providing selective permeability for ions, nutrients, metabolites and a host of other molecular species that otherwise lack a conduit into or out of cells. The lab will study integral membrane transporters that play vital roles in neurotransmitter uptake and drug efflux using a multi-disciplinary approach involving X-ray crystallography and other biochemical and biophysical methods. Background. My early training was in pharmaceutical sciences at Osmania university, as an undergraduate (2000-2003). I subsequently did a PhD with Dr. Yogendra Sharma and Dr. Rajan Sankaranaryanan at the Centre for Cellular and Molecular Biology, Hyderabad (2004-2009) where I carried out structural and biophysical studies of calcium-binding proteins. At CCMB, I characterized a novel calcium-binding motif in -crystallins and understood the interplay of divalent cations on neuronal calcium sensors. My active interest in diverse areas of neuroscience, pharmacology and membrane protein structure led me to Dr. Eric Gouaux's lab at the Vollum Institute, OHSU where I worked towards determining the first representative structure of a neurotransmitter transporter, a dopamine transporter (DAT) from fruit flies (2010-2015). This initial work led to further elucidation of DAT pharmacology through structures of DAT complexed with dopamine, cocaine, amphetamines and antidepressants (figure below). Awards and Fellowships. 1. 2. 3. 4. 5. Runner-up award at the K.V. Rao Young Scientist award-2008 for Biological Sciences. nd Abstract selected for the Finn Wold Travel award-2008 to attend the 22 Protein Society (USA) symposium on “Molecular machines in life”. Awarded the Eli Lilly Asia Outstanding thesis award-2009 (first prize). American Heart Association postdoctoral fellow for the duration of 07/2011 to 06/2013. Awarded “Ramanujam Fellowship” by the Dept. of Science and Technology, 02/2015. Selected Publications. (pubmed list) 1. Penmatsa, A.*, Wang, K. H.*, & Gouaux, E. X-ray structures of the Drosophila dopamine transporter in complex with nisoxetine and reboxetine. Nat. Str. Mol. Biol. (2015). (in press) 2. Wang, K. H.*, Penmatsa, A.* & Gouaux, E. Neurotransmitter and psychostimulant recognition by the dopamine transporter. Nature. (2015). 521, 322-327. 3. Wang, H., Goehring, A., Wang, K. H., Penmatsa, A., Ressler, R. & Gouaux, E. Structural basis for action by diverse antidepressants on biogenic amine transporters. Nature. (2013). 503, 141145. 4. Penmatsa, A.*, Wang, K. H.* & Gouaux, E. X-ray structure of dopamine transporter elucidates antidepressant mechanism. Nature. (2013). 503, 85-90. 5. Aravind, P.*, Mishra, A.*, Suman, S. K.*, Jobby, M. K., Sankaranarayanan, R. & Sharma, Y. The -Crystallin superfamily contains a universal motif for binding calcium. Biochemistry. (2009), 48, 12180–12190. 6. Aravind, P., Chandra, K., Reddy, P. P., Jeromin, A., Chary, K. V. & Sharma, Y. Regulatory and 2+ 2+ 2+ Structural EF-hand motifs of Neuronal Calcium Sensor-1: Mg modulates Ca -binding, Ca Induced conformational changes, and Equilibrium unfolding transitions. J. Mol. Biol. (2008), 376, 1100-1115. (* indicates equal contribution)