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Sunish Radhakrishnan

Technical Summary

Despite in-depth insights into many developmental signalling processes, the top-tier signalling cascades that couple cellular metabolism to cell cycle progression are poorly understood. One consequence of a change in cellular metabolism is an altered reduction-oxidation (redox) potential of the cell. Remarkably, recent evidence points towards the importance of cytoplasmic redox in regulating diverse events ranging from development to survival and virulence in bacteria. Our group is interested in answering key questions concerning: (i) The metabolic inputs controlling cytoplasmic redox (ii) The primary cell cycle/developmental regulators that respond to changes in metabolism or cytoplasmic redox and (iii) The use of metabolism-influenced cytoplasmic redox as an entry point to modulate cell cycle controls and thus influence differentiation, proliferation, and pathogenesis. Towards this, we use a combination of genetic, biochemical and imaging-based approaches in the genetically tractable bacterial model, Caulobacter crescentus, which depends on an oscillating cytoplasmic redox during the cell cycle to control development. We aim to decipher the essential signalling cascades that integrate metabolism to cellular development in bacteria. Such an understanding will help us to discover new therapeutic entry points in our combat against bacterial pathogens.

Figure 1

Selected publications

Narayanan, S., Kumar, L., and Radhakrishnan, S.K. (2018) Sensory domain of the cell cycle kinase CckA regulates the differential DNA binding of the master regulator CtrA in Caulobacter crescentus. BBA Gene Regul Mech 1861(10): 952–961.

Janakiraman, B., Mignolet, J., Narayanan, S., Viollier, P.H. and Radhakrishnan, S.K. (2016) In-phase oscillation of global regulons is orchestrated by a pole-specific organizer. Proc Natl Acad Sci USA 113(44): 12550-12555.

Narayanan, S., Janakiraman, B., Kumar, L., and Radhakrishnan, S.K. (2015) A cell cycle-controlled redox switch regulates the topoisomerase IV activity. Genes Dev 29: 1175-1187.

Joshi, K.K., Bergé, M., Radhakrishnan, S.K., Viollier, P.H., and Chien, P. (2015) An adaptor hierarchy regulates proteolysis during a bacterial cell cycle. Cell 163: 419-431.