BoseDASGUPTA'S  LAB

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-parasite interactions, the role of certain host factors as well as parasite virulence factors. We are trying to develop a host-directed immunomodulatory therapy using drug loaded, surface functionalized mesoporous particles in an aerosolic formulation that would overcome the mycobacteria-induced macrophage activation block and thereby kill the parasite. In parallel we are also engaged in developing a low-cost, point-of-care diagnostic kit for extreme drug resistant TB, which would give results in hours rather than a month.
In context of Leishmaniasis we have characterized DNA Topoisomerase IA from Leishmania (LdTOPIA), which is a prokaryotic TopA homolog, is absent in higher eukaryotes and is an essential enzyme to resolve polycistronic transcription generated R-loops in the near-intron less Leishmania genome. Through inhibitor screening we have identified tricyclic anti-depressants (TCA’s) as potent inhibitors of LdTOPIA. Through drug repurposing we are generating TCA derivatives with increased efficiency which we plan to encapsulate in surface functionalized physiological agents and deliver through reticuloendothelial blockade. Apart from this we are studying the role of host factors that enable controlled phagosome maturation allowing efficient promastigote to amastigote differentiation as well as factors that dampen macrophage proliferation but promotes amastigote proliferation.

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