Bhupendra N Singh, Ph.D.
Chief Scientist,Chairperson - Division of Microbiology
Functional genomics of mycobacteria and Sigma factor regulon
Tuberculosis continues to be a menacing disease causing millions of death worldwide annually. Research in my laboratory focuses on different aspects of mycobacterial biology and host pathogen interactions. We are trying to understand: 1. the regulation of kas operon gene expression in mycobacteria, 2. Decoding regulatory networks of sigma factors in mycobacteria. We use a range of genetic, microbiological, biochemical and cell biology approaches to answer questions pertaining to these areas. We have successfully created several knock out mutants (single as well as double mutant) of sigma factors in different species of mycobacteria. The mutant strains were characterized employing microarray based genome wide gene expression and 2D based proteome analysis in order to decode their regulon. Some of these mycobacterial sigma factors are required for virulence in cellular and mouse models of infection. We have found some interesting phenotypes of these mutants, and based on our regulon studies, we are in process of decoding the functions of specific genes regulated by these sigma factors, contributing to these phenotypes.
In addition to this, my lab is working to decode the regulation of kas operon genes in FAS-II pathway of mycobacteria. Findings from this study led to the genesis of recombinant mycobacterial strains using pathway specific inducible promoters in fusion with reporter genes in order to develop rationale based screen systems for screening of anti-mycobacterial compounds.