Cellular metabolism and energetics have emerged as key determinants of almost all biological processes from development to disease and even evolution. It is important to note that molecular factors involved in these processes are implicated in life-style disorders (diabetes/obesity), aging and age related diseases (cancer/neurodegeneration).
We employ a systems approach to investigate molecular mechanisms that couple metabolism to cellular and organismal physiology. Using diverse model systems and approaches that scale in length, size and time, we have discovered novel phenomena and mechanisms that drive cellular processes. We study Sirtuins, NAD-dependent protein deacylases, as candidate factors to understand dietary influence on cells and organisms. Specifically, we investigate the functions of key members of the Sirtuin family in regulating chromatin (epigenetics), gene expression, intra-cellular signaling, mitochondrial functions, and energy and metabolic homeostasis.
Our current interests are aimed at unraveling mechanisms that mediate state-reversals and physiological transitions. Using both experimental approaches and mathematical modeling, we have gained novel insights into how molecular-oscillations/-anticipations, and time-integral responses collectively contribute towards physiological homeostasis. We are motivated to discover molecular evolution of physiological responses whose abrogation causes metabolic diseases (diabetes/obesity), aging and cancer.