Investigating the role of TRIM33 in the DNA damage response in Multiple Myeloma

Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. Genomic instability is a hallmark of MM with almost all patients displaying cytogenetic abnormalities including ploidy changes, deletions, amplifications and translocations. Deletion of 1p is a common recurrent genetic event in MM with prognostic significance. Within this deleted region we have identified the E3 ligase TRIM33 as a potential tumour suppressor gene. Low expression of TRIM33 is significantly associated with disease progression and poor overall survival and overexpression of TRIM33 inhibits proliferation of MM cell lines.

Recent studies have identified a role for TRIM33 in the PARP-dependent DNA damage response (DDR) pathway. Preliminary studies in our group demonstrate that MM cell lines with low TRIM33 expression exhibit higher baseline DNA damage and an increased sensitivity to DNA damaging agents. This project will build on these studies to characterise the tumour suppressor activity of TRIM33 and delineate its role in DDR pathways in MM using techniques such as ChIP-Seq and ubiquitination assays to identify targets of TRIM33. We will investigate whether DNA repair defects associated with TRIM33 loss contribute to tumourigenesis and explore opportunities to therapeutically exploit DDR deficiencies in patients exhibiting loss of TRIM33.

ENTRY REQUIREMENTS

Candidates should have or expect to obtain a 2:1 or higher Honours degree or equivalent in a relevant biomedical or life sciences subject.

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

The English Language Unit (ELU) 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 from the ELU http://www.qub.ac.uk/tefl/