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Principal Investigator

Dr. Prasanna Venkatraman

Principal Investigator

Research Interests

Protein-protein interactions (PPI), typify physical, signalling and regulatory networks that orchestrate cellular responses. PPI are sensitive to levels, mutations, post translational modifications (PTM), and subcellular boundaries. Cancer cells exploit these to rewire networks to maintain mosaic correlations that allow them to survive. The lab tries to understand PPIs at different hierarchical levels with a long term goal is to expose the Achilles heel in cancer.

Current activities include:

  • Mapping the molecular details of individual PPIs and characterizing the hot spot sides of interaction
  • Exploiting them for the design and evolution of inhibitors
  • Structure guided construction of first neighbourhood subnetworks.
  • Inferring function and regulation through domain motif interaction
  • Expanding the networks by expression analysis and APMS derived PPI
  • Deriving context specific pathways that can be described by edge level metrics.

Looking for a talented post doc to conduct research on the following topic

Structure guided proteomics to reconstruct the composition of proteasome and stoichiometry of subunits in cancer cells

We have recently found out that the proteasome composition and activity in cancer cells is dynamic and regulated by assembly chaperones in novel ways than has been envisaged so far. Systematic investigation and careful analysis using CRISPR KO of the assembly chaperones have led to the hypothesis that the cancer proteasome network is rewired primarily due to RNA correlation loss. We would like to now understand the structure of the proteasome as is in the cancer cells using elegant biochemical experiments coupled to mass spectrometry, in vitro and ex vivo live cell activity assays. We believe that this leap in technology will help reconcile the many counter intuitive observations about the cancer cell proteasome, identify the regulatory mechanisms behind the assembly and structure and recognize the Achilles' heel in the proteasome network that eludes inhibition by active site inhibitors.

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RESEARCH

The lab is interested in the general understanding of the mechanism of cellular homoeostasis both in health and in disease. Synthesis of proteins, their ability to go from a linear polypeptide chain into a final folded structure, the specific functions that they carry out and finally their degradation are tightly and spatio-temporally controlled processes. Any aberration in the above processes is responsible for patho-physiological conditions seen in a multitude of diseases. They believe that dissecting the fundamental mechanism behind these processes will help in better understanding of the global aberrations observed in diseases like cancer and help in the development of new strategies for therapeutic interventions. Along these directions we are currently focusing on the structural, mechanistic and cell biological aspects of protein degradation by a self compartmentalized ubiquitous, ATP dependent regulatory protease called the Proteasomes.

There research now includes a new addition- a molecule from the cell signaling family - 14-3-3 zeta. They have been drawn to this molecule due to its surprising role in functioning as a molecular chaperone. The structural requirement of this protein to function as a chaperone and the identification of a novel ATP binding motif responsible for this function is being investigated. they are keen to explore if this is a unifying principle across the protein family with different isoforms

Lab Members

Alumni

PUBLICATIONS

Contact

Office Contact

Dr. Prasanna Venkatraman

KS 137, Advance Centre for Treatment Research & Education in Cancer, Tata Memorial Centre, (ACTREC), Plot No. 1 & 2, Sector 22, Kharghar, Navi Mumbai-410210. Maharashtra India.+91 (022) 2740 5000/ 6873 5000 Extn-5091 vprasanna@actrec.gov.in Lab Website

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