The laboratory is dedicated to the structural and molecular understanding of protein folding and stability, protein-protein interactions and structure-function relationship in proteins. The ubiquitous nature of a new class of hemoglobins in plants, the presence of novel hemoglobins in the microbial world, and the discovery of new hemoglobins in humans and other vertebrates have bolstered the hemoglobin research over the last several years. A major focus of the laboratory is the investigation of novel algal, plant, bacterial and animal hemoglobins involving techniques like laser flash photolysis, stopped-flow spectrometry, FTIR and EPR spectroscopy, site directed mutagenesis, computational biology and X-ray crystallography. Emphasis is on deciphering the mechanism of regulation of ligand binding in novel (hexacoordinate and truncated) hemoglobins in general. The goal is to be a part of the effort to set up a ‘biophysical fingerprint’ for novel hemoglobins that can help assign physiological functions. Other related proteins like hemoglobin reductases are being simultaneously investigated for a better understanding of function(s) of the novel globins. Stability, aggregation and protein folding problem related to classical and novel hemoglobins as well as hemoglobin based artificial blood substitutes is being simultaneously investigated. Comprehensive knowledge accumulated by hemoglobin researchers world-wide may be useful in improving oxygen transport and storage in mammalian circulatory systems, nitrogen fixing efficiency in plants, sensing and response to hypoxic conditions, scavenging efficiency under stress, and our ability to use heme protein based artificial oxygen carriers. The latter is being fervently pursued in the laboratory because of its translational value in medicine. The laboratory is also focused on spectroscopic and mass spectrometric characterization/screening of hemoglobin disorders with a goal to set up a simple, fast, economic and reliable diagnostics for such disorders using very small amounts of samples. The group is further engaged in understanding the pathophysiology of sickle cell disease using metabolomics and proteomics approaches and is attempting to decipher effective therapeutics to combat the debilitating disease, with promising success.

 

Structure-based rational drug discovery and design is currently the major emphasis of the laboratory. The aim is to seek structural insight of human dopamine b-hydroxylase (DBH) and ADP Ribosylation Factor Like Protein 15 (ARL15), drug targets for complex traits. Availability of the three-dimensional structures of these proteins will help detailed investigation of the structure-function relationship in these important enzymes and lay a platform for rational therapeutic drug design. The laboratory is currently focused on the discovery of potential small molecule inhibitors of DBH and ARL15 to combat cardiovascular diseases and rheumatoid arthritis, and a few lead molecules have emerged that might be developed as drugs for the target non-communicable diseases. On the other hand, there are attempts to identify small molecules to combat infectious diseases like leishmaniasis, as well as cancer.