Biochemical regulation at neuronal synapses

Higher order brain functions such as learning and memory arise from fundamental biochemical events occurring in the nervous system. Signal transduction mediated by Ca2+ is involved in a variety of physiological events at neuronal synapses. The spatio-temporal variations in the magnitude of Ca2+ signals give rise to varied physiological responses ranging from Long Term Potentiation (LTP) that underlie learning and memory to excitotoxicity that leads to neuronal death. CaMKII plays an important role in decoding Ca2+ signals. Our group is interested in understanding structure-activity relationships and protein-protein interactions of CaMKII. Although the interaction of CaMKII with the N-methyl-D-aspartate (NMDA)-type glutamate receptor is known to occur in vivo, the structural details as well as the functional significance of this interaction are still not clearly understood. Currently we are focusing our efforts on identification of the amino acid residues of both the proteins that make mutual contacts using a combination of site-directed mutagenesis and binding assays under in vitro as well as under intracellular conditions. For expression of the proteins we use E.coli, Baculovirus/insect cell system and HEK-293 cells. The functional consequences of this interaction are also being investigated. We are also searching for other proteins, which may be involved in binding interactions with CaMKII.

Bioprospecting for Neuropharmacological compounds

Excitotoxicity is a cause of neuronal damage in many neuropathological conditions such as epilepsy, reperfusion injury, etc. We are involved in establishing an in vitro excitotoxicity model using cell culture, which could be used to screen extracts from plants for their effects on excitotoxicity.