Projects:
- Chromatin recognition and remodeling by protein complex machinery and chromosome condensation with an emphasis on its role during DNA damage.
- Role of Arps in chromatin recognition and remodeling
- Mycobacterial SOS response and adaptation role of Nucleases in DNA repair
- Functional roles of Mycobacterial Toxin-Antitoxin modules
- Implications of environmental microbiology (Microbial dynamics in Water, Glacier, Soil and Air): Research activities include identification of microorganisms with the capability of degrading xenobiotics, heavy metals, pesticides and organic wastes. Further, we are interested in screening soil and water resources for discovering novel therapeutic agents against MTB and other infectious (ESKAPE) diseases.
Research Interests
1. Dynamics of Chromatin Remodelling
The higher order organization of the chromatin governs and dictates the regulation of several cellular processes that deals with DNA. ATP-dependent chromatin remodeling complexes (CRCs) and modifying enzymes are important protein machineries that remodel or modify the higher order chromatin structure to sense and repair DNA damages. Chromatin constitutes a physical barrier to DNA repair machineries to reach the DNA. In order to deal with this impediment, transient chromatin structural changes are integral to different DNA repair pathways. The interactions between the DNA repair proteins and components of the CRCs, seems to be important for the regulation of DNA repair. However, the relation between CRCs and DNA repair proteins are not completely understood. Several studies show that INO80 CRC found in eukaryotes contains actin and several actin related proteins, play important roles in homologous recombination and DNA repair. Our laboratory is interested in examining the roles of Nuclear Actin and Actin Related Proteins (ARPs) in chromatin remodeling complex with the aim to understand their molecular mechanisms in chromatin targeting and remodeling. To fully understand the mechanism of action of chromatin remodeling complexes, it will be necessary to determine how their activities are regulated; how they are targeted to specific genes; how they interact with histone-modifying enzymes and other regulatory proteins modulate chromatin. Our laboratory uses several model organisms such as, Saccharomyces cerevisiae, and Ustilago maydis to address these important issues.
2. DNA Damage Response of Mycobacterium tuberculosis
In response to continuous DNA damage, the bacterial cells employ specific DNA repair systems that help maintain genome integrity. The first response towards DNA damage is the induction of SOS response, which involves expression of several genes, which participate in a variety of DNA metabolic activities such as replication, repair, recombination and mutagenesis. Under normal growth conditions the SOS genes are expressed at a basal level, which increases distinctly upon induction of the SOS response in many bacterial species including Mycobacterium tuberculosis. M. tuberculosis (Mtb) are a dreadful pathogen which survives within the hostile environment of macrophage; hence it is not surprising that it would employ a highly efficient DNA repair machinery to exist in such an environment. Mycobacterial genome contains several putative HNH Nucleases, Toxin-Antitoxin module and Methyltransferases under the SOS regulon. Our lab is focused to understand the role of SOS regulated Nucleases in DNA repair. Investigation of these Nucleases will provide a new direction to our understanding of Mycobacterial DNA repair and also the strategy it adopts to survive within the macrophages.
In response to continuous DNA damage, the bacterial cells employ specific DNA repair systems that help maintain genome integrity. The first response towards DNA damage is the induction of SOS response, which involves expression of several genes, which participate in a variety of DNA metabolic activities such as replication, repair, recombination and mutagenesis. Under normal growth conditions the SOS genes are expressed at a basal level, which increases distinctly upon induction of the SOS response in many bacterial species including Mycobacterium tuberculosis. M. tuberculosis (Mtb) are a dreadful pathogen which survives within the hostile environment of macrophage; hence it is not surprising that it would employ a highly efficient DNA repair machinery to exist in such an environment. Mycobacterial genome contains several putative HNH Nucleases, Toxin-Antitoxin module and Methyltransferases under the SOS regulon. Our lab is focused to understand the role of SOS regulated Nucleases in DNA repair. Investigation of these Nucleases will provide a new direction to our understanding of Mycobacterial DNA repair and also the strategy it adopts to survive within the macrophages.
Funding:
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