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Regulation of human tRNA metabolism during stress and diseases

   Medical Research Council Toxicology Unit

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  Dr R Sawarkar  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Applications are invited for a 4 year PhD studentship within the Sawarkar lab at the MRC Toxicology Unit, University of Cambridge.

Human cells are constantly exposed to environmental stress. We have evolved elaborate mechanisms to mount appropriate response to adapt to the stress. The transcriptional branch of the stress response has been intensely investigated focussing primarily on protein-coding genes. Our current work has identified that tRNA synthesis is highly regulated during stress. How stress affects RNA Polymerase III that transcribes tRNA remains unknown We have conducted genome-wide CRISPR-Cas9 screen and identified several trans-regulators of this process. The project will investigate how these trans-regulators communicate with stress-signalling pathway and how the pathway is modified in cancer and neurodegeneration with the hope of identifying therapeutics.

The Medical Research Council (MRC) Toxicology Unit is a leading International Research Institute within the School of Biological Sciences, University of Cambridge. The Unit delivers mechanistic toxicology research, pursuing hypothesis-driven toxicological questions with a particular focus on the study of the causal links between exposure to endogenous and exogenous toxicants, molecular initiating events and adverse outcome pathways. The Unit's overall aims are to carry out pioneering research which leads to improved health and to train and mentor the next generation of toxicologists.

The Unit provides a supportive learning environment designed to meet the scientific and transferable skills required for an internationally competitive career. Our PhD Programme aims to train the scientific leaders of the future, giving them rewarding research projects with access to world-class facilities and expertise.

Applicants should have or shortly expect to obtain a first or good upper second-class degree from a UK university, or an equivalent standard from an overseas university, in a relevant subject such as Biomedical Science. Strong analytical skills, in addition to creativity, curiosity, enthusiasm, and the ability to work in a team are essential.

Application Process

You are strongly recommended to contact the project supervisor prior to submitting your formal application to find out more about the project and eligibility: Dr Ritwick Sawarkar

Information regarding the application process can be found at: PhD Programme | MRC Toxicology Unit (

All formal applications will need to be made through the University Application Portal:

PhD in Biological Science (MRC Toxicology Unit) | Postgraduate Admissions (

Your online application must include:

• A CV, including full details of all University course grades to date -

• Contact details for two academic or professional referees

• A personal statement of interest

Closing date: Friday 31st March 2022 or until a suitable candidate is found. Early applications are recommended.

Funding Notes

Full funding covering Maintenance and the University Composition Fee (Home Fee rate) and is provided for the studentship, with effect from 1 October 2023.
Maintenance fee is currently £19,250.
This studentship is open to UK citizens or overseas students who meet the UK residency requirements (home fees) or are able to augment the funds to cover the extra costs associated with international student fees. Full details of the University's entrance requirements are specified here: View Website.


Transcriptional lockdown during acute proteotoxic stress.
Sawarkar R. Trends Biochem Sci. 2022 Aug;47(8):660-672.
Stress-induced nuclear condensation of NELF drives transcriptional downregulation.
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. Mol Cell. 2021 Mar 4;81(5):1013-1026.e11.
Nascent-protein ubiquitination is required for heat shock-induced gene downregulation in human cells.
Aprile-Garcia F, Tomar P, Hummel B, Khavaran A, Sawarkar R. Nat Struct Mol Biol. 2019 Feb;26(2):137-146.
Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1.
Antonova A, Hummel B, Khavaran A, Redhaber DM, Aprile-Garcia F, Rawat P, Gundel K, Schneck M, Hansen EC, Mitschke J, Mittler G, Miething C, Sawarkar R. Cell Rep. 2019 Nov 5;29(6):1645-1659.e9.
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