Research Interest

Single-molecular Biophysical Chemistry

The intracellular environment is crowded with proteins, lipids, nucleic acids, salts, and polysaccharides. These occupy 30-40% of the cellular volume, and the viscosity is 4-5 times higher than the buffer. Present literature confirms that protein's behaviors (c.a. structure, dynamics, activity, folding-unfolding kinetics, stability, aggregation) are largely different in a crowded milieu compared to that in buffer solution. However, most biophysical studies are still carried out in dilute buffer solutions. It is, therefore, essential to understand the mechanism of macromolecular crowding. Obviously, the biological system is complex, so complex that it is probably impossible to understand/predict their behavior. However, with proper physical insight, one might make a logical guess. The main aim of my Ph.D. project is to understand such physical insight in a better way. Cell extract should be the best candidate to assess the crowding effect. However, doing an experiment and analyzing the result in such a complex entity is difficult and does not generally give any mechanistic view. Globular proteins are the next most relevant biological crowders. However, to have some insight into the mechanism of a complex process, a systematic study is essential where one component of the complexity is varied systematically, keeping others fixed (to eliminate their effect). Such a study is not possible with globular proteins. The best alternatives are the synthetic macromolecular crowders, which are available and can be synthesized with various sizes, shapes, and charges. It can mimic two most important phenomena: lesser available space and increased viscosity of a biologically crowded environment. Any field truly progresses only when there is proper physical insight. My thesis will aim to have this important mechanistic insight into protein behavior in a crowded environment.

Current Research Problem:

(i) How the macromolecular crowding effect depends on the size, shape, and charge of the Crowder.

(ii) How macromolecular and molecular crowding differs. 

(iii) What is the role of associated water structure and dynamics in controlling protein behavior in a crowded milieu?