Research Projects

Leishmaniasis, being a neglected tropical disease remains one of the major global health hurdle. Globally the number of cases are increasing and the disease continues to affect indigent communities in both developed and developing nations. The identification of safer and more effective therapeutic targets is hampered by the lack of understanding of the parasite's essential biological functions despite advances in drug development. Our research focuses on investigating redox proteins as potential drug targets. One such redox sensitive protein is Universal Minicircle Sequence Binding Protein (UMSBP), which remains uncharacterized. It has been found to play a key role in DNA replication by binding to the origin of replication site in the kinetoplast minicircle, but its exact mechanisms remain unknown. A recent study on Trypanosoma brucei, which is close relative of Leishmania donovani showed that this protein is interacting with core histone proteins and thereby helping in decondensation of DNA for replication. The sequence similarity of T. brucei UMSBP and L. donovani UMSBP is 55%. Here we are proposing that characterization of this protein and a detail study on protein-protein interactions between Ld UMSBP and histone proteins provides insights into the mechanism by which this protein aids in DNA replication. Additionally, knockout studies of this protein help elucidate its role in parasite survival. By understanding these mechanisms in Leishmania donovani, UMSBP can emerge as a potential drug target in treating the leishmaniasis infection. The key experiments designed to achieve the proposed objectives of the study are cloning, expression, purification and characterization of Ld UMSBP, structural analysis using advanced techniques like CD and NMR spectroscopy. Protein-protein interactions studies using co-immunoprecipitation and kDNA condensation/decondensation assays to understand its role in chromatin remodelling. Ld UMSBP gene knockouts studies, analysing mitochondrial functions, ROS generation, and intracellular calcium levels, colocalization by fluorescent microscopy. Insilco studies including virtual screening, molecular docking, and simulation to identify potential molecules that can inhibit the activity of Ld UMSBP. The significance of this study is to identify potential therapeutic target by elucidating important mechanisms associated with UMSBP in parasite survival. If this project objectives are achieved Ld UMSBP will be established as potential therapeutic target by shedding light on unknown pathways that are crucial for parasite survival.