Research Projects

Visceral leishmaniasis, caused by Leishmania donovani, is a severe form of leishmaniasis with thousands of new cases annually, particularly in India. The lack of effective vaccines, limitations of frontline drugs, and resistance to existing drugs have led to the search for novel drug targets for the treatment of leishmaniasis. The protein-protein interaction network (PPIN) of L. donovani could provide insights into essential proteins with significant sequence divergence from their mammalian counterparts, which could provide the basis for identifying plausible therapeutic targets to overcome the disease. The objective is to perform protein-protein interaction studies, characterize them biochemically, and determine the three-dimensional structures of essential proteins using x-ray crystallography for identifying structure-based specific inhibitors. The methodology involves homology mapping for Leishmania proteins in the sTRING database, topological analysis, and biological data evaluation using the shinyGO 0.76 server. Essential proteins will be identified by integrating topological and biological properties. The ORFs of essential proteins will be cloned from L. donovani, expressed in E. coli, purified using affinity chromatography, and characterized using various methods. Purified proteins will be subjected to crystallization, and suitable crystals will be used for diffraction data collection using an x-ray source. The data will be processed, merged, and scaled, followed by model building, refinement, and analysis of structure. structure-directed specific inhibitors will be identified and assessed for their inhibitory properties in L. donovani.