Parashar Lab
Using a combination of structural (X-ray crystallography) and functional analyses, our laboratory determines the mechanistic basis of critical communication events during bacterial pathogenesis and phage defense. This facilitates development of a novel class of anti-infectives that do not kill bacteria but target these communication events to curb bacterial behaviors leading to disease.
Structural Biology of c-di-AMP Signaling
Inter- and intra-cellular communication is a basic and vital process for survival and growth of living organisms. A number of nucleotides are used as “second messenger” (intracellular) signals to regulate physiological functions in both prokaryotes and eukaryotes. One such second messenger signal molecule, cyclic-di-AMP (c-di-AMP) regulate genomic integrity, cell wall homeostasis, biofilm formation, virulence, induction of host immune responses, and development of resistance to -lactam antibiotics in bacteria. The intracellular concentration of this centrally important second messenger c-di-AMP is very critical to cellular physiology. However, the mechanisms of the precise regulation of c-di-AMP levels and c-di-AMP-mediated changes in gene expression are not completely understood. We study how c-di-AMP levels are regulated and how c-di-AMP exerts its effect on the activity of receptor proteins in mediating its downstream functions.
Structural Biology of Second Messenger Regulation of Abortive Viral Infections
We employ structural biology coupled with biochemical and genetic analysis to understand the mechanistic details of second messenger regulation and function during abortive viral infections in bacteria.
DR. PARASHAR'S POSTODOCTORAL RESEARCH
Rap proteins regulate bacterial development in response to cell-cell communication signals. Dr. Parashar's postdoctoral research depicted conformational life cycle of Rap family of quorum sensing receptors in Gram-positive bacteria. This depicted a unique example of protein function regulation by a conformational switch that involves expansion of a protein's repeat domain. On left, Rap proteins are shown in their unbound (apo), target protein bound, and regulatory peptide bound states.
LABORATORY EQUIPMENT AND FACILITIES
Our laboratory is equipped with all the basic instruments required for macromolecular crystallography and protein biochemistry. We have state-of-the-art AKTA PURE and AKTA FPLC systems in lab for protein purification. We have Jansi UVEXp crystal imaging system housed in the laboratory. We have high-throughput crystallization facility is conveniently located in the lab. We have Microscale Thermophoresis equipment to study affinity between molecules. X-ray facility is located in the Chemistry and Biochemistry department which is 5 minutes walk from the lab. We have access to shared facilities in common areas in the department of Medical Laboratory Sciences.
WORK FLOW
Dive right into our laboratory as a new comer, and you will be exposed to one of the following steps in the work flow for structural biology. Starting from cloning genes, we don't stop until we see the target protein in it's three-dimensional form.