Cell biology/ Microbial biotechnology/Protein Biochemistry
Using Bacillus lipase as a model system, we used error prone PCR based in vitro evolution
of the enzyme towards temperature adaptation and have probed the structure – function
correlation in this model system. We successfully cloned and expressed several lipase
genes from different niches, generated thermostable and cold adaptive variant enzymes and
deciphered the correlated alterations in its structure with variable function. Pilot
experiments are being carried out for the application of these enzymes.
• Another area of active pursuit in my lab, in which significant contributions has been made,
is screening of the leads from natural products for anticancer activity. We are
investigating the molecular mechanisms of their action and exploring their use in the
development of anticancer therapeutic agents. An extension of this work is to understand
the epigenetic regulation of cell cycle genes in the cells.
• Presently my research is focused on identifying new therapeutic interventions/diagnostics
for TB. Lipid metabolism was reported to be crucial for the infection/intracellular survival
of mycobacteria. Mycobacteria have large number of lipolytic enzymes. My group
characterized several lipolytic enzymes in terms of function (LipN/ xenobiotic degradation,
MestT/epoxide degradation, mbtJ/iron stress), immune-modulation(Rv0774c, LipQ,LipV)
and their potential role in the intracellular survival in host immune cells. The expression of
these genes during dormant and actively growing stage were analysed by transcriptome
analysis. Few essential lypolytic enzymes were identified by antisense technology/gene
knockout. Identifying and targeting these proteins could provide a new prescriptive for
developing new TB drugs. After ensuring, the crucial role of these proteins, virtual
screening and molecular dynamics approaches are being used to identify the potential
inhibitors against these proteins. On the other hand attempts are being made to understand
the mechanism of drug resistance. The estimation of structural changes due to point
mutations in different genes in drug resistant mycobacterium has been studied to get
comprehensive account of the different enzyme activity/ correlation with drug resistance.
Attempts are being made to use proteins/peptides showing humoral response to develop
peptide based diagnostic kit.