Abstract
Cyclic adenosine and guanosine monophosphates (cAMP and cGMP) are used extensively in developing the syntax of cellular communication in pathogenic bacteria and their mammalian hosts. Over the years, we have addressed at the molecular level the way cyclic nucleotides are used by pathogens that cause two important diseases, namely Tuberculosis and Diarrhea. I will first describe how mycobacteria have evolved novel strategies for the generation, degradation and utilization of cAMP. Here we have discovered the unique allosteric regulation of protein acetylation by cAMP, with important implications in fatty acid metabolism by mycobacteria. In the second part of the talk, I will describe the role and regulation of a gut-associated receptor guanylyl cyclase that is the target for bacterial enterotoxins that cause watery diarrhoea. Our contributions in the analyses of human mutations in this receptor, that result in congenital and constitutive diarrhea, have paved the way for the development of animal models that may mimic human diarrhea, as well as provide avenues for the translation of our findings to clinically relevant therapeutic strategies in future.
Bio
Sandhya S Visweswariah completed her M.Sc. in Chemistry from the Indian Institute of Technology, Kanpur and her PhD from the Department of Biochemistry, Indian Institute of Science. She worked as a post-doctoral fellow and scientist in Astra-Zeneca Research Centre in Bangalore, but returned to academia when she took up a position in the Indian Institute of Science in 1993. Her research interests have mainly focussed on the role of cyclic nucleotides in cellular biology. She has been involved in discovering novel mechanisms of cyclic AMP-mediated signalling in Mycobacteria, and elucidated the importance of receptor guanylyl cyclases in regulating gut homeostasis and disease. She has spent several months on sabbatical in the University of Missouri, and the University of California at Berkeley. Recently, as a Nehru-Fulbright Senior Research Fellow, she worked in the Department of Microbiology and Immunology in Weill-Cornell Medical College, New York. She is currently the Astra Zeneca Research Professor in the Indian Institute of Science. She serves on the Editorial Boards of a number of journals, is a Fellow of the Indian National Science Academy, the Indian Academy of Science, and is a JC Bose National Research Professor.