Investigating the functional consequences of HUWE1 mutations in Multiple Myeloma

D2_042_Research_V2

CCRCB

Funded PhD Opportunity

Investigating the functional consequences of HUWE1 mutations in Multiple Myeloma

PROJECT DESCRIPTION

Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells. An active area of research in MM is focused on developing strategies to target enzymes within the ubiquitin proteasome system. We have identified deregulated expression of the E3 ligase HUWE1 in MM. HUWE1 is a large HECT domain E3 ligase that regulates a number of proteins involved in oncogenic transformation, including MYC and MCL-1. Novel driver mutations in HUWE1 have recently been reported in a specific cytogenetic subgroup of MM patients. A variety of mutations were identified in patients, including a recurrent splice site mutation and mutations in the dimerization interface of HUWE1, which acts as a key regulatory site for HUWE1 activity.

The aim of this PhD is to investigate the functional consequences of HUWE1 mutations in MM. We have identified a number of HUWE1 mutant MM cell lines and this project will generate additional mutant cell lines using CRISPR/Cas9 genome editing technology to give a panel of cell lines that reflect the spectrum of clinical mutations observed. An ELISA-based activity assay will be developed both to determine whether specific mutations alter HUWE1 activity and to screen novel inhibitors of HUWE1.

In addition, the effect of mutations on relevant protein substrates of HUWE1 will be investigated.  
 

FUNDING 

*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.

ENTRY REQUIREMENTS 

Candidates should have or expect to obtain a 2:1 or higher Honours degree or equivalent in a relevant field, such as the life sciences, maths, physics, or computer science 


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/

SUPERVISORS

Dr L Crawford

Prof K Mills

CLOSING DATE

Sunday, January 20, 2019

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.

HAVE A QUESTION?

EMAIL US

Queen's University Belfast is committed to Equality, Diversity and Inclusion.
For more information please read our Equality and Diversity Policy.

Queen's University Belfast is registered with the Charity Commission for Northern Ireland NIC101788
VAT registration number: GB 254 7995 11