Kanchan Garai
Tata Institute of Fundamental Research

Associate Editor
Biophysical Reports

What are you currently working on that excites you?

We are focused on uncovering the mechanisms of liquid-liquid phase separation (popularly known as LLPS) of proteins. LLPS involves separation of biomolecules such as proteins and RNA into liquid droplets. It enables organization of cellular components without the need for membrane-bound compartments. It is crucial for normal cellular functions, such as gene expression regulation, signal transduction, and the formation of stress granules. However, LLPS can also lead to growth of abnormal protein aggregates, commonly known as amyloid fibrils. For instance, in Alzheimer’s disease, the tau protein—critical for stabilizing microtubules—can undergo LLPS, resulting in the formation of neurotoxic aggregates. We use single molecule techniques to study the process of LLPS and amyloid aggregation with single molecule sensitivity and resolution. Our goal is to understand the underlying pathways and to devise strategies to prevent the transition of the proteins of interest from the soluble to the insoluble phase.

What has been your biggest “aha” moment in science?

A few years ago, we were trying to investigate interaction of lipids with amyloid-beta peptide, a small protein involved in Alzheimer’s disease. We tried various experiments but didn’t find any significant interaction. In the meantime, we built a total internal reflection fluorescence (TIRF) microscope to visualize and study growth of the aggregates, viz, amyloid fibrils starting from the soluble peptide. Once again, the lipids didn’t affect the growth of the fibrils. However, we started observing something entirely new: spherical liquid-like condensates of lipid-amyloid-beta complexes. This started a new direction of research in my lab.