TIFR
Department of Chemical Sciences
School of Natural Sciences

Tracking the Molecular Players in Neurodegenerative Disorders

Research Highlight11

As part of Molecular Biophysics and Imaging and the Chemical Biology and Bioinorganic Chemistry groups, we are investigating biophysically tractable yet biologically interesting systems, using (mostly) spectroscopic and imaging tools, most of which we build ourselves. Our recent focus has been on two problems: protein misfolding/aggregation, and vesicular neurotransmission. Both of these interface with the phenomenon of amyloid induced neuro-degeneration, which results in such well known and untreatable diseases such as Alzheimer’s and Parkinson’s.

Alzheimer’s Amyloid beta is a small peptide, and therefore expected to be more tractable at a molecular level compared to typical proteins. Yet it is uniquely interesting in the biological context. We have developed single molecule level fluorescence tools specifically suited for studying amyloid misfolding and aggregation. Techniques such as Fluorescence Correlation Spectroscopy, Forster Resonance Energy Transfer, Fluorescence Lifetime Imaging, Surface Enhanced Raman Scattering, and Atomic Force Microscopy are used to look at the structure-function relationship of aggregation-prone proteins.

On the other hand, vesicular neurotransmission is a multifaceted phenomena and therefore difficult to simplify beyond the level of single neurons. However, monoaminergic vesicles can be tracked with unique label-free multiphoton microscopy techniques that we have developed in the lab. We hope that a combination of these techniques, together with other tools such as solid state Nuclear Magnetic Resonance Spectroscopy and Peptide Engineering, will help us uncover the fundamental mechanisms underlying protein misfolding, aggregation and toxicity.

The work described here, undertaken in the last few years, involve different aspects of these themes. In addition, development of biophotonic instrumentation and methodology has been a frequent offshoot of this work in the lab. Some of these tools have been commercialized (e.g. http://www.holmarc.com/fcs.html), and we have also initiated training programs and annual workshops to facilitate sharing and dissemination of Biophotonic knowledge and techniques within India. The National Fluorescence Workshop (www.fcsworkshop.in), the National Photonics Fellowship of India (www.photonicsindia.org) and the Biophysics Pashchim Meetings Series (https://sites.google.com/site/biophysicspaschim/) were initiated by our lab. For further information, visit our lab website.