Dr. Kushi Anand Post Doctoral Researcher under Dr. Amit Singh, CIDR received Early Career Fellowship (2018) from Wellcome-DBT India Alliance.This fellowship is for postdoctoral scientists who wish to undertake high-quality research and establish themselves as independent researchers in India. The Wellcome Trust/DBT India Alliance is an £160 million initiative funded equally by the Wellcome Trust, UK and Department of Biotechnology, India. The broad aim of the India Alliance is to build excellence in the Indian biomedical scientific community by supporting future leaders in the field.
Title of the project:
Understanding the regulatory role of G-quadruplex in modulating gene expression in Mycobacterium tuberculosis (Mtb).
About the project:
In addition to classical B-form structure, DNA adopts several non-canonical secondary structures: one that received much attention over past several decades is G-quadruplex (G4). Studies have demonstrated the formation of these structures under diverse physiological conditions and performing multiple biological roles in a range of organisms. More importantly, G4-motifs are enriched in telomeres and promoters of many oncogenes, suggesting an important regulatory role in the cancer cells. Consistent to this, targeting G4-motifs is actively under consideration for cancer therapy. In contrast to mammalian systems, the occurrence and importance of G4 structures are not well characterized in bacteria. A few studies indicate that G4 contributes to phase variation and mediate radio-resistance in some bacteria. In this context, genome of one of the most successful human pathogen Mtb, is 65% GC-rich and has recently been shown to contain islands of putative G4 forming motifs in the upstream region of coding sequences as well as in the structural regions of many genes. Despite this knowledge, we lack a deeper insight on the importance of such structure in regulating gene expression, physiology, and virulence properties of Mtb. The main objective of his proposal is to comprehensively dissect the molecular mechanism of G-quadruplex (G4) mediated regulation of gene expression and its influence on stress tolerance and persistence of Mycobacterium tuberculosis (Mtb) during infection. Investigating influence of G4 motif in Mtb genomes will provides fresh insight into physiological roles of G4 in the context of Mtb pathogenesis. Results from such a comprehensive study will not only deepen our understanding of previously uncharacterized relation between functionally important G4 and virulence in Mtb but also open up new avenues of fundamental and translational researches which will most likely aid in better tuberculosis management.