Epigenetic regulation of SARS-CoV-2 infection, inflammation and cellular stress response
A number of external factors such as infection, therapeutics and abiotic stimuli lead to inflammatory reactions in healthy individuals. While the signalling pathways leading to inflammation have been extensively studied, how chromatin and epigenetics control inflammatory response by influencing transcription remains poorly studied. We have recently shown that stress converges on a specific transcriptional output that we have defined as SITA (Aprile-Garcia et al, 2019, Nature Struct Mol Biol). SARS-CoV-2 infection causes a similar SITA response in lung epithelial cells (Weigang et al, in submission). Liquid-liquid phase separation and biomolecular condensation of transcriptional regulators underlie SITA (Rawat et al, 2021, Mol Cell).
The proposed project will investigate epigenetic regulation of SITA and stress response in the context of inflammation using mouse models and cell-culture systems. The project will be carried out in close collaboration with Novartis and AstraZeneca with an opportunity for industrial training for the PhD student.
This is an MRC Integrative Toxicology Training Partnership (ITTP) studentship and includes specific training opportunities, including a week away to attend toxicology training for all members of the scheme.
The MRC Toxicology Unit is a leading international research Unit providing state of the art research facilities, with excellent opportunities for collaborative interaction within a vibrant community at the University of Cambridge.
There are a variety of training modules and courses which students are encouraged to attend. In addition, students follow the Toxicology Unit’s weekly external and internal seminar programs and are included in the postdoc/student forums which take place each month and offer excellent opportunities for collaboration and career development.
Key references:Weigang S et al, Sawarkar R (in submission) SARS-CoV-2 causes global chromatin changes in host cells defining therapeutic opportunities.
Rawat et al, Sawarkar R (2021) Stress-induced condensation of NELF drives transcriptional downregulation. Mol Cell. doi: 10.1016/j.molcel.2021.01.016.
Antonova et al, Sawarkar R (2019) Heat-shock protein 90 controls the expression of cell-cycle genes by stabilizing metazoan-specific HCFC1. Cell Reports. 29(6):1645-1659.
Aprile-Garcia et al, Sawarkar R (2019) Nascent protein ubiquitination is required for heat-shock induced gene downregulation. Nature Structural and Molecular Biology. 26(2):137-146
Candidates must expect to obtain qualifications at the level of a first-class or 2.1 Honours Degree in a related discipline and must be enthusiastic to collaborate closely with other members of the team.
In addition to an excellent academic record, we are also looking for candidates with hands-on experience in one or more of the following areas: Molecular cell biology, immunology, inflammation biology, genomics, chromatin research, bioinformatics, in vivo mouse biology.
Funding is available at the level of Home Fees and a stipend of £17,500 per annum.
Information regarding eligibility for Home Fee classification can be found at:https://www.postgraduate.study.cam.ac.uk/finance/fees/what-my-fee-status
It is strongly encouraged that you contact the supervisor prior to making your formal application – Ritwick Sawarkar firstname.lastname@example.org
Further information can be found at the MRC Toxicology Unit Website: https://www.mrc-tox.cam.ac.uk/postgraduate/applications
Informal enquiries are invited and can be directed toRitwick Sawarkar at email@example.com
If you have any queries regarding the application process please contact Bronwen Chamberlain at firstname.lastname@example.org
Please quote reference PU25771 on your application and in any correspondence about this vacancy.
The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.
The University has a responsibility to ensure that all employees are eligible to live and work in the UK.