Vigyan Yuva awardee Radhakrishnan Mahalakshmi: Decoding complex proteins

Radhakrishnan Mahalakshmi, professor of biological sciences at the Indian Institute of Science Education and Research, describes her work with beta-barrel membrane proteins.

This year’s Yuva Vigyan Shanti Swarup Bhatnagar award for Biological Sciences is shared by two scientists who study membrane proteins, but of different kinds. Radhakrishnan Mahalakshmi, professor of biological sciences at the Indian Institute of Science Education and Research (IISERB), describes her work with beta-barrel membrane proteins, and its implications for therapeutics.

Radhakrishnan Mahalakshmi.

What I do

I study beta-barrel membrane proteins, which are a unique kind of membrane protein with unique functions. Beta-barrel proteins are involved in transport of a wide variety of molecules from ions to proteins, and are indispensable to the survival of the cell. I try to understand how beta barrel membrane proteins fold, which refers the process of its conversion into a compact defined structure, and how this folding relates to regulation at the molecular level.

How I do it

Beta-barrel membrane proteins are extremely difficult to study, which is why we know very little about them. I study them through various biophysical methods. We study these proteins at the molecular level, that is at the level of amino acids, which are the building blocks of proteins. Through the methods I have developed, I have successfully identified unique regulators of folding, stability and function for these proteins. This information will help me design peptidomimetics (these are protein-like structures that scientists create to mimic proteins and peptides) as next-generation therapeutics.

My multifaceted approach to membrane protein biophysics is the first of its kind in India, and is also very unique globally. Thus far, no other laboratory anywhere has successfully integrated membrane protein folding kinetics with thermodynamic equilibrium and a coupled single molecule-in vivo functional study for human mitochondrial beta-barrels.

Using the information I have successfully obtained, I plan to design novel peptidomimetics as next-generation therapeutics to target antibiotic resistance (in TB and other bacterial diseases), cancer, and neurodegeneration.