Molecular Immunology and Cellular Microbiology Laboratory

In context of the Indian sub-continent, Tuberculosis and Visceral Leishmaniasis are dreadful infectious diseases caused by Mycobacterium tuberculosis and Leishmania donovani respectively. The advent of extreme drug resistance has aggravated the situation. The search for newer molecular targets as well as alternative therapeutic strategies is clearly evident.
Using CRISPR/Cas9 mediated genome editing our lab tries to have a thorough understanding of the host factors governing parasite pathogenesis. We are looking into the roles of phosphatases and kinases in mediating parasite survival. Biochemical assays are being set-up for the functional characterization of macrophage factors phosphorylated by mycobacteria secreted virulence factors. Functional characterization and adaptive resistance mechanism studies are carried out for an essential Leishmania enzyme. Besides, the role of host factors that enable controlled phagosome maturation allowing efficient promastigote to amastigote differentiation as well as factors dampening macrophage proliferation but promoting amastigote proliferation would be studied.
We are also trying to envisage into host-directed immunomodulatory therapeutics against mycobacterial and leishmania infection that would overcome the pathogen-induced classical macrophage activation block and thereby re-enable them to kill the parasite. Drug repurposing approaches against a Leishmaniaspecific essential enzyme using tri-cyclic anti-depressants are also being carried out whose application through the creation of reticulo-endothelial blockade would be tried out.  We are also engaged in developing a rapid, low-cost, point-of-care diagnostic kit for extreme drug resistant TB