This project will begin on 26 September 2022
STING regulates the innate immune response to viral infection but is also activated in response to DNA damage. This project aims to provide a comprehensive and unbiased analysis of the role of Ub mediated STING regulation in response to DNA damage and its impact on innate immune activation.
STING is an essential protein involved in innate immunity. Physiologically, STING-mediated inflammation is driven by accumulation of DNA/chromatin in the cytosol. STING activation leads to a Type I interferon response, leading to inhibition of viral replication and modulation of the adaptive immune response (e.g. T- & B-cell recruitment/functional modulation) through transactivation of chemokines. Following viral infection, STING activity can be regulated by ubiquitination (Ub), which is modulated by a number of deubiquitinating enzymes (DUBs). STING can also be activated by self-DNA in the cytosol, which contributes to a number of disease pathologies including autoimmune and aging diseases and cancer.
Importantly, we have previously demonstrated STING activation following DNA damage from exogenous and endogenous sources such as chemotherapeutics and DNA repair deficiencies. However, the role of Ub mediated STING regulation following DNA damage remains poorly understood. Elucidation of STING regulation by Ub in the context of DNA damage will provide insight into the underlying biological mechanisms of innate and adaptive immune activation in cancer and following cancer therapy. This proposal aims to provide a comprehensive and unbiased analysis of the role of Ub mediated STING regulation in response to DNA damage using state of the art techniques including SILAC Mass-spectrometry mediated Ubiquitination site mapping and CRISPR screening combined with single cell RNA-sequencing (scRNA-Seq), to identify functionally important STING DUBs and molecular biology mediated characterisation of these DUBs with the aim of identifying potential therapeutic targets for inflammatory diseases, including cancer.
Funding eligibility: ROI (and EU applicants with pre-settled/settled) status may be eligible for funding. Please review the DfE T&C’s.
ENTRY REQUIREMENTS
You must hold or expect to get an upper second class honours degree from a university in the UK or Ireland, or qualifications and experience considered by the University as equivalent to that standard. Candidates who already hold a doctoral degree, or who have registered on a PhD for one year (or part-time equivalent) are not eligible.
English Language
Candidates applying from countries where the first language is not English should produce evidence of their competence through a qualification such as IELTS or TOEFL score.
The minimum recommended score for the School of Medicine, Dentistry and Biomedical Science is:
· IELTS score of 6.0 with not less than 5.5 in each of the four component elements of listening, reading, speaking and writing taken within the last 2 years;
· TOEFL score of 80+ (internet basted test), taken within the last 2 years, with minimum component scores of; Listening 17, Reading 18, Speaking 20, Writing 17);
· A valid Certificate of Proficiency in English grade A or B;
· A valid Certificate of Advanced English grade A; or
· A first or upper second class honours degree from a university based in the UK, Republic of Ireland or other suitably quality assured location in a country deemed by the UK Border Agency to be majority English speaking.
For a list of English Language qualifications also accepted by the School and University please see the following link:
http://www.qub.ac.uk/International/International-students/Applying/English-language-requirements/#English
INTO Queen’s English Language Courses offers both pre-sessional and in-sessional courses in English for academic purposes and study skills. Courses vary in length and full information can be obtained at: https://www.qub.ac.uk/International/International-students/Applying/University-Preparation-Courses/INTOEnglishlanguagecoursesatQueens/
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