Red blood cells, Disease and Chemical Biology

Red blood cells (RBC) in the circulating blood do not contain a nucleus and devoid of any active machinary to synthesize proteins. It is loaded with >95% of hemoglobin (Hb), transports oxygen and is under high oxidative stress. During a normal life span of 120 days in circulation, the protein loads in erythrocyte cytosols remain more or less unaltered. However, the levels of soluble proteins and organization of membrane associated proteins show significant changes under disease conditions. My research interests have centered around the proteins and lipids of RBC. I started working on spectrin, one of the major protein of the membrane skeleton, responsible in maintaining the mechanical flexibility of RBC through the formation of a meshwork in the inner face of the cell surface membrane. Spectrin is a 100 nm long thread with a 3-helix bundle motiff repeated to form the chain. We identified few biologically relevant hotspots in the polypeptide chain. After the emergence of proteomics in early 2000 as the successor to genomics, we became interested in profiling of RBC proteins from normal and diseased samples, the most well characterized cellular component of blood. While working to find correlations between the levels of different proteins in the blood samples of patients and the severity of the disease, we found differential expression of two major classes of proteins, the redox regulators and molecular chaperones both in sickle cell disease and thalassemia. After leaving Biophysics & Structural Genomics Division in 2014, I’m back to spectrin and the major goal is to establish connectivity between the membrane skeleton, lipids of the membrane and the RBC proteome. I’d try to build up the chemical biology story from two major phases of my research in SINP, (1) the year 1994 till 2002 and (2) the year 2003 till 2014.