Ritwick Sawarkar

Biography:

Ritwick studied Microbiology and Biochemistry in Mumbai (India) and obtained his PhD in 2010 from Indian Institute of Science, Bangalore. Ritwick then moved to the Department of Biosystems Science and Engineering of ETH-Zürich in Basel (Switzerland) as a postdoctoral fellow with Renato Paro. In 2014, Ritwick started his own independent group at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg (Germany), before moving to the MRC Toxicology Unit in 2019. Ritwick received the ERC Consolidator Grant in 2018 and Alfred Tissières Young Investigator Award in 2019.

Research Interests:

The molecular mechanisms by which chromatin exerts control over stress response is the main focus of the Unit programme. We aim to address the following questions:

Which cellular pathways sense environmental stress/ toxins and signal to the genome?
How does chromatin interpret the information about cellular health and toxic exposure determining the transcriptional response to stress?
How does the transcriptional response adapt cellular phenotypes to survive the stress?

We study these three questions in the context of cellular exposure to environmental stress as well as small-molecule therapeutics in collaboration with pharmaceutical companies. Our approaches include genomics, single-cell transcriptomics, proteomics, chromatin biochemistry as well as genome-wide screening to identify novel components of stress-response pathways. Discovery-driven global approaches in mammalian cells are further validated by in vitro reconstitution experiments and mouse genetic models. We aim to gain novel insights and mechanistic understanding of transcriptional response to stress and toxins.

Publications

Key publications:

Leone S, Srivastava A, Herrero-Ruiz A, Hummel B, Tittel L, Campalastri R, Aprile-Garcia F, Tan JH, Rawat P, Andersson P, Willis WE, Sawarkar R. HSP70 binds to specific non-coding RNA and regulates human RNA polymerase III. Mol Cell. 84(4), 687-701, (2024).

Rawat P, Boehning M, Hummel B, Aprile-Garcia F, Pandit AS, Eisenhardt N, Khavaran A, Niskanen E, Vos SM, Palvimo JJ, Pichler A, Cramer P, Sawarkar R. Stress-induced nuclear condensation of NELF drives transcriptional downregulation. Mol Cell. 81 (5), 1013-1026, (2021)

Antonova A, Hummel B, Khavaran A, Redhaber D, Aprile Garcia F, Rawat P, Gundel K, Schneck M, Hansen E, Mitschke J, Mittler G, Miething C and Sawarkar R. Heat-shock protein 90 controls the expression of cell-cycle genes by stabilizing metazoan-specific Host-Cell Factor HCFC1. Cell Reports. 29(6):1645-1659. (2019)

Aprile-Garcia F, Tomar P, Hummel B, Khavaran A and Sawarkar R. Nascent-protein ubiquitination is required for heat shock-induced gene downregulation in human cells. Nat Struct Mol Biol. 26(2):137-146. (2019)

Hummel B, Hansen EC, Yoveva A, Aprile-Garcia F, Hussong R and Sawarkar R. The evolutionary capacitor HSP90 buffers the regulatory effects of mammalian endogenous retroviruses. Nat Struct Mol Biol. 24, 234-242. (2017)

Sawarkar R, Sievers C and Paro R. Hsp90 globally targets paused RNA polymerase to regulate gene expression in response to stimuli. Cell. 149(4):807-18. (2012)

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