The research is primarily focused on understanding protein-lipid interactions which are crucial for designing novel therapeutics related to neurodegenerative disorders. We use different biochemical and biophysical techniques to measure such interactions, and we also develop label-free, free solution binding assays to measure these challenging interactions label-free and immobilization free using a lab built interferometric set-up, Compensated Interferometric Reader (CIR).
For example, a label free assay was developed by Ray et al. to measure GPCR-lipid interaction in a physiological environment. The description can be found in the paper linked.
Project 1: Lipid-chaperone interactions
Lipids due to their amphiphilic nature, possesses non-specific interactions. CIR measures only the RI induced conformational changes, hence by subtracting the bulk signal from the control, combination of FSA and CIR is able to quantify the specific interactions of a lipid with proteins. Hence, we develop label-free assays to quantitatively measure the challenging specific interactions of lipids with proteins using our FSA-CIR approach.
Project 2: GPCR-ligand interactions in native environment
We are developing bottom-up synthetic membrane platform to quantify agonist recognition by GPCRs using the label-free free-solution assay. In this project, we will be isolating the GPCR in synthetic membrane and measure their affinity towards agonists or antagonists using the label-free assay. We will then compare the binding interactions of GPCR isolated in cell vesicles (more native form) to compare the systematic contribution of the recognition parameters in these type of interactions. Currently, we are working with 5HT4 receptor because activation of serotonergic neurotransmission has recently emerged as a promising therapeutic strategy for Alzheimer's disease (AD).