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Dr. R Harinarayanan
Home >> Bacterial Genetics
Bacterial Genetics

The main focus of the lab is to understand physiological functions regulated by the modified nucleotides (p)ppGpp and the protein factor DksA that works in concert with (p)ppGpp. The regulations brought about by these factors are more generally referred to as the stringent response, which is conserved across bacteria. Studies so far have implicated the small molecules and DksA in the co-ordination of growth and associated cellular processes with nutrient availability, but the molecular mechanisms involved are not fully understood. In the model organism Escherichia coli, we have used the synthetic lethal screen to genetically discern cellular processes compromised in cells with altered (p)ppGpp pool and investigated the molecular underpinning for the phenotypes. The genetic screen has revealed the role of (p)ppGpp and protein co-factor DksA in the regulation of membrane biogenesis, cell division and translation, fundamental cellular processes conserved across life forms. Our results implicate a role for the stringent response factors in prevention of ribosome arrest during translation and consequently the need for rescue of stalled ribosomes. Mechanistic basis for alleviation of ribosome stalling is being investigated. With respect to lipid synthesis and cell division, presently our results point to at least two scenarios, namely, initiation of lipid biosynthesis and maintenance of unsaturated fatty acid to work in tandem with (p)ppGpp and DksA and modulate cell division. We have identified a novel protein (FabY) involved in membrane biogenesis that can compensate for function performed by FabH, one of three β-ketoacyl-acyl carrier protein synthase (KAS) required for membrane biogenesis and the primary catalyst in the initiation of fatty acid biosynthesis. Regulation of FabY is being investigated.

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Email: hari<at>cdfd.org.in
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Last updated on: Monday, 5th June, 2023

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