Assessing the epigenetic changes associated with on-target CRISPR-induced toxicity
“On-target” CrispR/Cas9 toxicity remains poorly understood. In these cases, Cas9 will cut the desired location, but rather than the excision repair mechanisms restoring the DNA, a double stand break (DSB) can occur. DSBs are highly toxic to the affected genome if not rapidly corrected, with the potential to form chromosomal translocations, micronuclei, chromothrypsis and cell death.
The proposed project aims to explore whether the epigenetic architecture of a chosen target site impacts on the potential for these DSBs to occur. Further to this, the project will explore whether modifications to the Cas9 enzyme will further influence the potential for on-target toxicity to occur. An array of imaging and molecular biology techniques, alongside next-generation sequencing and bioinformatics skills will be utilised by the successful candidate to answer these questions.
This studentship is based in the MRC Toxicology Unit and there will also be the opportunity to spend time at the Astra Zeneca labs for a period of the PhD.
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.
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.
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 Mathew Van De Pette firstname.lastname@example.org
Further information can be found at the MRC Toxicology Unit Website: https://www.mrc-tox.cam.ac.uk/postgraduate/applications
If you have any queries regarding the application process please contact Bronwen Chamberlain at email@example.com
Please quote reference PU25774 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.