My research is focused on the understanding molecular basis of signal transduction using state-of-the-art solution NMR spectroscopy, small-angle X-ray scattering, and molecular biophysics tools to answer critical biological questions stemming from protein-protein, protein-lipid, and protein-small molecule interactions.
Project 1: Development of Lipid-Nanodiscs approach to study single transmembrane proteins. Lipid-Nanodiscs are discoidal shape particles, that provide a native-like lipidic environment to membrane proteins to retain their structure and function. These nanoparticles of biological membrane composition are thermostable and suitable for spectroscopic analysis. Here, we develop and optimize the membrane scaffold peptide (MSP) towards the formation of nanodiscs that can accommodate the single transmembrane protein using multiple tools of molecular biophysics. Hence this will provide a unique opportunity to investigate the structure and dynamics of the membrane proteins in a native environment.
Project 2: Structural biochemistry of T-cell exhaustion pertaining to immune checkpoints.
T cell exhaustion is a condition where T cells fail to prevent an immunopathological condition arising from chronic antigen stimulation either in cancer or chronic infection. Molecular receptors known as immune checkpoints related to T-cell exhaustion express on T-cells and regulate the process. Despite the understanding of exhaustion events at the cellular level, the structural basis of the molecular events is still unclear. We will use the in-lab developed novel lipid-nanodisc approach to reconstitute the full-length immune checkpoints (PD-1, CTLA-4, TIM-3, Lag-3, and Tigit) for in vitro structural and functional characterization. In collaboration with the Götz lab at SDSC-UCSD, we are working on the spatial organization of immune checkpoints using all-atom simulations.