Dissecting the role of the epigenetic reader TRIM33 in Multiple Myeloma

Dissecting the role of the epigenetic reader TRIM33 in Multiple Myeloma
Project Description
Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. Altered epigenetic regulation of gene expression is emerging as an important player in MM pathogenesis. Through previous studies we have identified the epigenetic reader protein TRIM33 as a potential tumour suppressor gene in MM. Loss of TRIM33 is observed in approximately 20% of MM patients and is significantly associated with disease progression and reduced overall survival.
Conversely, overexpression of TRIM33 in MM cell lines inhibits proliferation. TRIM33 contains a PHD and bromodomain which bind histone 3 at trimethylated lysine 9 (H3K9me3) and acetylated lysine 18 (H3K18ac), respectively. A number of recent studies point to a role for H3K9 methylation in MM. This study aims to delineate the role of TRIM33 in H3K9 methylation and determine its functional significance in MM. TRIM33 loss-of-function and gain-of-function isogenic cell lines will be generated using CRISPR/Cas9 gene editing technology and used to characterize the epigenomic and gene expression changes associated with TRIM33 loss in MM. There is an ever growing list of epigenetic therapies that are under investigation in MM.
It is anticipated that this study will identify therapeutic vulnerabilities in MM that may be targeted by some of these agents.
SUPERVISORS
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/
CLOSING DATE
Sunday, January 20, 2019
Funding Notes
*FUNDING CONFIRMED – Leukaemia & Lymphoma NI*
Eligibility for both fees (£4260 for 2018/19, 2019/20 TBC) and maintenance (£14,777 for 2018/19, 2019/20 TBC) depends on the applicants being either an ordinary UK or EU resident.
How to Apply
Please refer to 'Entry Requirements' for specific admissions criteria.
Apply online via the Queen's on-line application portal . Guidance is available on the University’s Prospective Student pages.
When applying for a project, please choose ‘MEDICINE’ as your subject area/School.
Please ensure you adhere to the closing dates.
If you have any further queries please contact: pgoffice.smdb@qub.ac.uk or +44 (0) 28 9097 2619/2042.
Please visit the School of Medicine, Dentistry and Biomedical Sciences, Centre for Cancer Research and Cell Biology, website for further details about the Centre.