Dr. Samrat Mukhopadhyay
Professor, Biological Sciences & Chemical Sciences

Email:               mukhopadhyay(AT)iisermohali.ac.in

Phone:

Fax:                  +91 172 2240266

Personal Page:  The Mukhopadhyay Research Group

  

Research Area:

Chemical Biology and Biophysics: Conformational Characteristics and Phase Transition of Intrinsically Disordered Proteins, Liquid-Liquid Phase Separation, Misfolding, Aggregation and Amyloid Formation; Fluorescence and Raman Spectroscopy and Microscopy; Nanoscale Biophysics.

 
Research Focus

Proteins are the workhorses of the living systems. Traditionally, protein function was thought to depend on a unique well-defined 3D structure that is encoded by the amino acid sequence. However, current investigations have revealed that a large fraction of the proteome consists of polypeptide segments that lack a well-defined structure under physiological conditions. They belong to a distinct class of proteins termed as intrinsically disordered proteins (IDPs) that challenge the tenets of the traditional structure-function paradigm. The intrinsic disorder in the proteins allows the complex organisms to carry out multiple functions from the same proteins by adopting different conformational states. However, the disorder-to-function relationship is poorly understood. Additionally, dysfunction of many IDPs is associated with a range of deadly diseases such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), frontotemporal dementias (FTDs) and cancers. The Mukhopadhyay lab utilizes a diverse range of approaches involving biophysics, biochemistry, chemical biology, cell and molecular biology, and advanced single-molecule and ultrafast spectroscopy to gain molecular insights into the conformational ensemble and dynamics, the protein hydration water, liquid-liquid phase separation, aggregation and amyloid formation from various IDPs containing low-complexity and prion-like domains. These studies are beginning to illuminate the unique molecular insights into the pivotal functional and pathological aspects of phase transition of IDPs.


Selected Publications

  • "An intrinsically disordered pathological prion variant Y145Stop converts into self-seeding amyloids via liquid-liquid phase separation" A. Agarwal, S.K. Rai, A. Avni & S. Mukhopadhyay* Proc. Natl. Acad. Sci. USA (2021)118, e2100968118
  • "Catalytic coacervate crucibles” S. Mukhopadhyay* Nature Chemistry (2021) 13, 1028-30 (News & Views).
  • "Hofmeister Ions Modulate the Autocatalytic Amyloidogenesis of an Intrinsically Disordered Functional Amyloid Domain via Unusual Biphasic Kinetics" P. Dogra, S.S. Roy, A. Joshi & S. Mukhopadhyay* J. Mol. Biol. (2020) 432, 6173-86.
  • "The Dynamism of Intrinsically Disordered Proteins: Binding-Induced Folding, Amyloid Formation, and Phase Separation" S. Mukhopadhyay*. J. Phys. Chem. B. (2020) 124, 11541–60 (Feature Article).
  • "Intermolecular Charge-Transfer Modulates Liquid-Liquid Phase Separation and Liquid-to-Solid Maturation of an Intrinsically Disordered pH-Responsive Domain" P. Dogra, A. Joshi, A. Majumdar & S. Mukhopadhyay* J. Am. Chem. Soc. (2019) 141, 20380-20389.
  • "Liquid-Liquid Phase Separation is Driven by Large-Scale Conformational Unwinding and Fluctuations of Intrinsically Disordered Protein Molecules" A. Majumdar, P. Dogra, S. Maity & S. Mukhopadhyay* J. Phys. Chem. Lett. (2019) 10, 3929-3936.
  • "Electrostatic lipid-protein interactions sequester the curli amyloid fold on the lipopolysaccharide membrane surface" H.M. Swasthi & S. Mukhopadhyay* J. Biol. Chem. (2017) 292, 19861-19872.
  • "Direct Observation of the Intrinsic Backbone Torsional Mobility of Disordered Proteins" N. Jain, D. Narang, K. Bhasne, V. Dalal, S. Arya, M. Bhattacharya & S. Mukhopadhyay* Biophys. J. (2016) 111, 768-774. 


For a complete list of publications: Click here