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Department of Genetics

 

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

Cells respond to environmental stress by mounting an adaptive stress response in order to survive stressful conditions. Transcriptional control is a major regulatory layer that determines the strength, the duration and persistence of cellular stress response. Transcription factors, chromatin modifications and non-coding RNA influence the transcriptional response to environmental stress. 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:

(i) Which cellular pathways sense environmental stress and signal to the genome?

(ii) How does chromatin interpret the information about cellular health and stress exposure determining the transcriptional response to stress?

(iii) 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.

Research Group Links

Sawarkar Group

MRC Toxicology Unit Sawarkar Program

Publications

Key publications: 

 

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. (2021) Stress-induced nuclear condensation of NELF drives transcriptional downregulation. Mol Cell. doi: 10.1016/j.molcel.2021.01.016. 

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 (2019) 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.e9.

Aprile-Garcia F, Tomar P, Hummel B, Khavaran A, Sawarkar R‘Nascent-protein ubiquitination is required for heat shock-induced gene downregulation in human cells.’ Nat Struct Mol Biol. 2019 Feb;26(2):137-146. doi: 10.1038/s41594-018-0182-x. Epub 2019 Feb 4. PMID: 30723328

Irmak D, Fatima A, Gutiérrez-Garcia R, Rinschen MM, Wagle P, Altmüller J, Arrigoni L, Hummel B, Klein C, Frese CK, Sawarkar R, Rada-Iglesias A, Vilchez D. ‘Mechanism suppressing H3K9 trimethylation in pluripotent stem cells and its demise by polyQ-expanded huntingtin mutations.’ Hum Mol Genet. 2018 Dec 1;27(23):4117-4134. doi: 10.1093/hmg/ddy304. PMID:30452683

Vincenz-Donnelly L, Holthusen H, Körner R, Hansen EC, Presto J, Johansson J, Sawarkar R, Hartl FU, Hipp MS. ‘High capacity of the endoplasmic reticulum to prevent secretion and aggregation of amyloidogenic proteins.’ EMBO J. 2018 Feb 1;37(3):337-350. doi: 10.15252/embj.201695841. Epub 2017 Dec 15. PMID:29247078

Full Publication List

PubMed

MRC Investigator, MRC Toxicology Unit
Dr Ritwick  Sawarkar
Areas of Interest: 
Chromatin control of environmental stress response
Email address: 
MRC Toxicology Unit
Gleeson Building
Tennis Court Road
Cambridge
CB2 1QR
Office phone: 
+44 1223 334706

Affiliations

Classifications: