Protein Acrobats 2016
Sivaraj (Shiv) Sivaramakrishnan
National Centre for Biological Sciences (NCBS), Bengaluru, India, Ph.D.
Almost 4% of the human genome encodes more than 800 GPCRs. Stimuli (ligands) sensed by the plethora of receptors are transduced to the cell, primarily by a limited number of G-proteins. A ligand bound receptor interacts with, and activates, a cognate G-protein; that in turn stimulates a downstream signaling pathway. The conserved general architecture of the interacting interfaces presented by various GPCRs allows for interactions with non-cognate G-proteins as well. I am employing SPASM biosensors to investigate the effect of interactions between receptors and non-cognate G-proteins, on downstream signaling.
Tata Institute of Fundamental Research (TIFR), Mumbai, India, Ph.D.
My research focus is myosin VI driven cargo transport and GPCR signaling. Regarding transport, I am interested in understanding how cargo adapters affect myosin VI motility. In GPCR signaling, I am trying to understand membrane compartmentalization of GPCR signaling.
Indian Institute of Technology, Chennai, India Ph.D.
Designing substrate-selective inhibitors has remained a large challenge despite kinases being an important therapeutic target. My project combines biophysical approaches with computational modeling to probe kinase-substrate specificity and identify new substrate-selective kinase inhibitors.
University of Pennsylvania, Ph.D.
Phosphorylation by protein kinases plays a critical role in the regulation of many cellular processes. My research examines the intra- and inter-molecular interactions of protein kinase C (PKC) domains and how these interaction are altered by binding of inhibitors. PKC isoforms are frequently mutated in cancer, so understanding the mechanisms of inhibition may be important for developing targeted cancer therapies.
Kyungpook National University (KNU), Daegu, South Korea, B.S.
The clinical significance of GPCRs is demonstrated in that approximately 40% of all prescription medication on the market target GPCRs. Understanding the mechanism of how drugs elicit their physiological responses through these receptors is crucial if we are to correctly evaluate, design, optimize, and discover new drugs. Currently, biochemical and structural studies of GPCRs lack the ability to fully explain how the binding of drugs to their target GPCRs leads to modulation of multiple downstream responses; while physiological studies fail to provide a comprehensive mechanism of the observed drug-induced responses. My project utilizes molecular and cellular biology, protein engineering, and DNA nanotechnology techniques to understand the biochemical and biophysical aspects that modulate the interaction between GPCRs and G proteins.
M.D./Ph.D. Graduate Student
Gustavus Adolphus College, B.S.
In collaboration with Keehun, Anja performs ballet in lab. She floats on air as she twists and adopts new conformations with her GPCRs.
Scientist / Lab Manager
Michigan State University, B.S.
Molecular motors are necessary for active transportation of cargo throughout the cell as well as the maintenance of certain cellular structures. I'm studying how interaction strength between motor and cargo influences the maintenance of these cellular processes. To do this, I'm using cellular localization tags to target myosin motors to specific cargoes with varying strengths of affinity.
University of Wisconsin-Madison, B.S.
There are over 800 G protein coupled receptors (GPCRs) in the human genome that couple to over 20 distinct G proteins. I am interested in the structural basis of selective pairing of GPCR-G protein pairings in cells. My project combines SPASM biosensors with molecular dynamic simulations (collaboration with Vaidehi Nagarajan at City of Hope) to dissect the structural mechanisms of GPCR signaling specificity.