Max-Planck Institute for Molecular Physiology, Germany
National Center for Biological Sciences, India
From the very beginning I was fascinated by the concepts that form the basics of cellular organization in biological structures. These often include signaling networks that arise from local interactions of proteins and fluctuations generating distinct network states thus leading to contrasting cellular behaviors. I first had the opportunity to study this in the lab of Prof. Philippe Bastiaens and Prof. Alfred Wittinghofer at Max-Planck Institute for Molecular Physiology, Germany. During my PhD, I utilized molecular, biochemical and cell imaging techniques to understand the molecular mechanism involved in maintaining the spatial organization of KRas. I was able to identify a key cytoplasmic factor PDEδ that enhances the encounter frequency of KRas to the plasma membrane. I also deduced an active displacement process by Arl2/3 that disrupts the PDEδ–KRas complex essential for reinstating KRas to the plasma membrane. This rationale was then applied to pharmacologically interfere the electrostatic interaction of KRas with charged plasma membrane to counter oncogenic KRas signaling.
As a Wellcome Trust/ DBT India Alliance Early Career Fellow at NCBS, Bangalore and the MRC-Cancer Unit, Cambridge, I would further investigate the nanoscale organization of Ras. My main objective is to gain a deeper insight into how the collective behavior of nanometer-sized Ras enriched domains with its surrounding lipids generates functional cellular structures on the micrometer scale.