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Dr.Bishwajit Kundu
Associate Professor
School of Biological Sciences

 

Research interests
Our group studies L-asparaginases from thermophilic and pathogenic bacterium and works on identifying their physiological function, engineering them to work under optimal physiological conditions and designing small molecules that could effectively block their activity. We are currently studying L-asparaginase from Pyrococcus furiosus (PfA), Mycobacterium, Leishmania and humans using both rational and semi-rational approaches.  We are focusing on studying individual protein domains of PfA and the implications of domain shuffling in the thermophilic and mesophilic counterparts. We recently showed that individual domains of PfA assemble into a global shape and quaternary structure similiar to the wild type protein. This conjoined tetrameric ensemble exhibited higher activity and stability as compared to the wild type PfA. (Tomar et al. Acta cryst. section D. 2014). Previously, we had created few active site mutants of PfA with comparatively better enzymatic properties at physiological conditions and improves the proteolytic resistance (US Patent No.9322008, Kundu et al. 2016). These PfA variants act as suitable antineoplastic agents with significantly higher cytotoxicity against range of cancerous cell lines.Moreover, we have proposed new mechanistic insights into the catalytic activity of thermophilic L-asparaginases recently (Bansal et al. FASEB J. 2012). Further, our studies on L-asparaginases from Leishmania Donovani (LdAI) gave new mechanistic insights on the structure & function of these enzymes (Singh J et al. Mol. Biosystems. 2015). The study resulted in identification of few strongly active compounds that may prove as effective anti-leishmaniasis molecules. Our group is currently involved in exploring the structural and functional aspects of these enzymes along with their homologues in humans and Mycobacterium.


Another major research focus of my group is the study of amyloids and the physico-chemical parameters responsible for inducing amyloidosis. We had previously proposed a mathematical model for identifying toxic peptide stretches which promote the alternate amyloidogenic structure attainment in proteins (Rana A et al. Biochemica et Biophysica Acta, 2008).  The findings were further confirmed using  carbonic anhydrase (BCA II) as a model system where in a detailed comparative of the amyloid forming steps and seeding propensities of toxic stretch and the entire protein has beeen explored (Garg & Kundu. Biochemica et Biophysica Acta, 2016). Besides, we recently showed that small molecule interception of toxic stretch in Gelsolin protein alters its amyloidogenic pathway. We presented molecular insights into the possible mechanism and showed how augmenting or stalling fibrillation in proteins may lead to reduction in amyloid toxicity (Arya P et al. ACS Chem. Neurosci, 2014). Currently, we are studying amyloid forming propensities of carbonic anhydrase mutants and spontenous conversion propensity of its toxic peptide stretches in isolation. Besides another focus is on identifying novel interacting partners of amyloidogenic proteins like Prion, Myostatin and Gelsolin for understanding molecular mechanisms of amyloid formation and exploring newer intervention strategies.

Current research