Investigating the functional consequences of HUWE1 mutations in Multiple Myeloma
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. 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.
Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. Proteasome inhibitors have provided significant therapeutic advance in the treatment of MM, however resistance and dose limiting side effects remain a clinical challenge. Recent research has focused on developing strategies to target other enzymes within the ubiquitin proteasome system. We have identified deregulated expression of the E3 ligase HUWE1 in MM and demonstrate that inhibitors of the E3 ligase HUWE1 lead to growth arrest of MM cell lines. 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. The most common mutation identified is a splice site mutation in the DUF913 (domain of unknown function 913) of HUWE1; the remainder are missense mutations distributed across the coding sequence including 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. Increased understanding of the mechanistic functions of HUWE1 will aid the development of strategies for pharmacologically targeting this enzyme in MM.
Dr Lisa Crawford
Full-time: 3 Years
The School of Medicine, Dentistry and Biomedical Sciences trains ~250 postgraduate research students undertaking PhD, MD and MPhil degrees in Cancer Research and Cell Biology, Experimental Medicine, Public Health, Medical Education and Dentistry. Its diverse postgraduate student population comprises both basic and clinical scientists from across the globe engaged in wide-ranging research projects spanning the breadth of the School’s research portfolio from traditional epidemiology to 'big data' science and bioinformatics, through molecular and cell biology to clinical trials.
- The School of Medicine, Dentistry and Biomedical Sciences promotes close collaborative interaction with local and global biotechnology companies, such as Almac and Randox. Such relationships are underpinned by innovative discovery science and its clinical application and have resulted in development of novel diagnostic/prognostic applications and therapies.
- The School of Medicine, Dentistry and Biomedical Sciences postgraduate programme trains students in both research-specific and generic skills towards promotion of professional development. Students may also avail of career development advice at the School annual Postgraduate Research Forum, through its peer mentoring programme, and as part of their individual Postgraduate Development Programme. The QUB Graduate School also provides wide-ranging opportunities for career development which complement School-specific postgraduate research training.
World Class Facilities
- As a member of the Russell Group of leading UK Universities, Queen’s University Belfast is committed to maintaining the very best research. In the last Research Excellence Framework exercise, 99% of our research environment was judged to be internationally-excellent or world-leading, whilst Queen’s was ranked joint 1st in the UK for research intensity. Queen’s are ranked 1st in the UK as the most entrepreneurial University. As such, Queen’s provides an ideal environment to support high-quality postgraduate research.
- Postgraduate students in the School of Medicine, Dentistry and Biomedical Sciences will undertake their research projects within the Institute of Health Sciences which has benefitted from significant recent investment (>£100M) and boasts state-of-art facilities and technology.
Internationally Renowned Experts
- Postgraduate students in the School of Medicine, Dentistry and Biomedical Sciences are closely supervised by experienced academic staff and are viewed as a central and critical component of their world-leading research programmes.
- The School of Medicine, Dentistry and Biomedical Sciences provides a vibrant environment for postgraduate research training. There are currently ~250 students undertaking wide-ranging basic science and clinical research projects who work closely together with postdoctoral and academic staff across the Institute of Health Sciences. Students are encouraged to interact both within and across disciplines through formal and informal School events, many of which are student-led.
Research students are encouraged to play a full and active role in relation to the wide range of research activities undertaken within the School and there are many resources available including:
- Opportunity to benefit from world-class infrastructure and academic faculty.
- Tailored postgraduate training programme including specific and generic aspects and careers-focussed peer mentoring.
- Access to the QUB Postgraduate Researcher Development Programme.
- Provision of shared laboratory and office space as required by research project.
Whilst I’m a Belfast native, I didn’t complete my Bachelor’s or Master’s degree at Queen’s. However, after attending Universities in Leeds, Melbourne, Gothenburg and Shanghai, I decided it was time to return to my home city to undertake my PhD at the Centre for Public Health. Two years in and I’m so happy with my decision. I feel very supported and valued here and have had the opportunity to get involved in various things outside of my research which has allowed me to develop personally and has enriched my experience at Queen’s.
The School has current collaborative partnerships with the NIH National Cancer Institute (Washington) and the Princess Margaret Cancer Centre (Toronto), together with developing relationships with international institutions in the Middle East, such as Hashemite University (Zarqa, Jordan). In addition, some of our current students conduct the majority of their research abroad (currently US and China) with supervisors from both QUB and the external institution. The School also supports short-term research training opportunities for its postgraduate students in the groups of international collaborators; these enriching experiences not only benefit the project but provide valuable insight into research in a global context.
Patrick G Johnston Centre for Cancer Research
The global burden of cancer is increasing with incidence now at 15 million new diagnoses each year. The Patrick G Johnston Centre for Cancer Research (PGJCCR) is attuned to this global health issue and specialises in integrating academic discovery, industrial/commercial enterprise and innovative health care practice to promote effective delivery of precision cancer medicine, to improve patient health and outcomes, generate wealth and alleviate suffering. PGJCCR has established successful multi-disciplinary teams focusing on cancers of Gastrointestinal, Prostate, Breast and Ovarian origin. Each team incorporates disease-specialist clinicians, accredited molecular pathology expertise bringing affiliated biobank tissue repositories, and academics skilled in the art of (i) biomarker discovery and bioinformatics, (ii) biological investigation and therapeutic development, and (iii) the prosecution of early-phase translation-driven clinical trials. Our significant success has resulted from a strong team-based approach.
Wellcome Wolfson Institute for Experimental Medicine
The Wellcome Wolfson Institute for Experimental Medicine (WWIEM) is committed to research excellence by making scientific breakthroughs in the mechanisms of disease, which we translate to innovative therapeutics to improve patient outcomes. We are an international hub of excellence on eye disease, infectious diseases and respiratory disease with a core emphasis on immunology, molecular cell biology and patient-based investigations. WWIEM comprises three main research themes focussed on Immunology and Microbes, Respiratory Medicine, and Vision and Vascular Medicine. Our Immunobiology and Microbes research group focusses on understanding the immune system which is essential for defence of the human body, not only in preventing a wide variety of diseases but also aiding recovery from them. Our Respiratory Medicine research group focusses on understanding the processes that lead to common lung illnesses such as asthma, cystic fibrosis, and acute respiratory distress syndrome. Our Vision and Vascular Medicine research group particularly focusses on inflammation within the cardiovascular system as a frequent cause of cardiac and other vascular diseases which represent a significant health burden on society. Our work makes an important impact in the fight against conditions such as diabetes, cardiovascular disease, and eye disease.
Centre for Medical Education
Research students joining the Centre for Medical Education will have the opportunity to develop an education project using a range of qualitative and quantitative methods, for which specific training is made available. Research encompasses a range of learning environments and spans the continuum of medical education. Projects are linked by an underlying commitment to improve patient care through education. Current research interests include GP pedagogy, technology-enhanced learning, identity, critical research, and diversity and inclusion. Students are mentored to develop their own research questions and methodologies within the broad remit of the Centre.
Centre for Public Health
The overall mission of the Centre for Public Health (CPH) is to improve health and reduce inequalities, prevent and manage chronic disease and disability more effectively, and to improve the delivery of health and social care. CPH comprises four main research themes focussed on Epidemiology and Public Health, Cancer Epidemiology, Nutrition and Public Health, and Health Services and Global Health. Our Epidemiology and Public Health research group harnesses Big Data in discovery science and its application to clinical and public health practice, to help to understand how both molecular biomarkers and environments (including social norms and networks) shape risk in individuals and populations. Our Cancer Epidemiology research group includes programmes focussed on pre-malignancy molecular epidemiology, gastrointestinal cancer progression and precision medicine, and pharmaco-epidemiology exploring the potential for drug re-purposing. Our Nutrition and Public Health research group works across the life-course to understand the determinants of a healthy diet in individuals, at risk groups (e.g. schoolchildren, pregnant women, older people) and whole populations, and on identifying ways to improve it. Our Health Services and Global Health research group focusses on health care for people with chronic conditions and poor mental health, quality improvement and implementation science, oral health and related cancers, trials methodology, health economics, and global eye health. Our Dentistry and Oral Health Care research has a focus on gerodontology, head and neck cancer, and nutrition.
Funded postgraduate research studentships are advertised on the School of Medicine, Dentistry and Biomedical Sciences website: https://www.qub.ac.uk/schools/mdbs/Study/PostgraduateResearch/CurrentOpportunities/.
We will also consider applications from externally or self-funded students who should identify potential academic supervisors aligned with their research interests: https://www.qub.ac.uk/schools/mdbs/Research/find-a-phd-supervisor/.
Please note that we can only support projects which fit within our main research themes of Experimental Medicine, Cancer Research and Cell Biology, Medical Education, Public Health and Dentistry .
The School of Medicine, Dentistry and Biomedical Sciences drives research excellence and impact, delivering innovative solutions to the specific challenges we have identified in healthcare. The School has three central aims:
(1) To address key global challenges in health care by making scientific breakthroughs in mechanisms of disease, translating these to innovative therapeutics and preventive interventions to improve patient outcomes.
(2) To establish lasting relationships with major funders for programmatic research and capacity building. This includes doctoral training, clinical academic programmes and postdoctoral fellowships.
(3) To leverage scientific strengths with small and medium size enterprises and large pharmaceutical companies to develop externally funded competitive, collaborative programmes for discovery and translation.
Current postgraduate research projects and potential opportunities.
As a member of the Russell Group of leading UK Universities, Queen’s University Belfast is committed to maintaining the very best research. In the last Research Excellence Framework exercise, 99% of our research environment was judged to be internationally-excellent or world-leading, whilst Queen’s was ranked joint 1st in the UK for research intensity. Queen’s are ranked 1st in the UK as the most entrepreneurial University. As such, Queen’s provides an ideal environment to support high-quality postgraduate research.
Current PGR Student Profiles
Current postgraduate research projects and potential opportunities.
The School of Medicine, Dentistry and Biomedical Sciences is dedicated to providing postgraduate research students with a supportive environment to effectively promote their education, training and professional development. Our students are highly valued as a central and critical component of the School’s research strategy and benefit from both exceptional facilities and supervision by world-leading academic researchers.
The majority of postgraduate research students within the School of Medicine, Dentistry and Biomedical Sciences continue to successfully secure appropriate employment upon completion of their studies. Chosen careers are generally relevant to their qualification within industry, academia and the National Health Service and have included postdoctoral research across the world, clinical/non-clinical academia, return to full-time clinical work, medical writing, industry research, management/financial consultancy, and R&D software development. The School runs a dedicated careers session at its annual Postgraduate Research Forum and careers-focussed peer mentoring from postdoctoral researchers whilst students are expected to discuss potential careers with their supervisors as part of their individual Postgraduate Development Programme.
Employment after the Course
All postgraduate research students can avail of careers advice from the Graduate School whilst postdoctoral employment opportunities are highlighted at the annual School Postgraduate Research Forum within a dedicated session. Students should also discuss potential careers with their supervisors as a central focus of their individual Postgraduate Development Programme.
Learning OutcomesAs a postgraduate student in the School of Medicine, Dentistry and Biomedical Sciences you will receive high-quality training and support for a career in scientific research with real potential to contribute to development of improved strategies for the management and treatment of life-threatening diseases.
Course structure1. The School of Medicine, Dentistry and Biomedical Sciences is dedicated to providing its postgraduate research students with a supportive environment to effectively promote their education, training and professional development. First year students enrol on a tailored training programme comprising a series of lectures, workshops and practical sessions focused on key research skills, including bioimaging, informatics, genomics, mass spectrometry, animal models and clinical trials. In addition, all students receive wide-ranging and ongoing training in generic and transferable skills, such as scientific writing, data analysis, presentation and critical appraisal, through dedicated communication courses and seminars. They also benefit from presentation of their research findings at major national and international conferences, which is an expectation of all postgraduate research students, and through regular interaction with the QUB Graduate School, whose specific function is to support postgraduate training, development and careers.
Students undertake their specific research project under the close guidance of an experienced principal supervisor with support from 1 or 2 co-supervisors as appropriate. All postgraduate research students are initially registered as ‘undifferentiated’ which means that they are required to complete a probationary period after which they are assessed for their suitability to undertake a postgraduate research degree during the differentiation process. Differentiation normally takes place at 9-12 months for full time students and 18-24 months for part time students. Each student is required to complete a literature review, give an oral presentation of their research within their Centre, and provide evidence of appropriate training and completion of their Postgraduate Development Plan. They are then interviewed by a differentiation panel, comprising 2 or 3 academic staff, who assess the students understanding of their project and progress, based on both their submitted paperwork and response to questions. Differentiated students are required to complete a similar Annual Progress Review process in each subsequent year of their research degree. The duration of a full-time PhD programme is normally 3-4 years. For completion of their doctoral qualification students are required to submit a thesis of their research of appropriate length and content (as advised by their supervisors) which will be assessed by oral examination conducted by an external and internal examiner.
Funded postgraduate research studentships are advertised on the School of Medicine, Dentistry and Biomedical Sciences website: https://www.qub.ac.uk/schools/mdbs/Study/PostgraduateResearch/CurrentOpportunities/ . We will also consider applications from externally or self-funded students who should identify potential academic supervisors aligned with their research interests: https://www.qub.ac.uk/schools/mdbs/Research/find-a-phd-supervisor/ Please note that we can only support projects which fit within the overall research strategy of the School and individual research focus of our academic staff.
Students who meet the eligibility criteria for postgraduate research should select ONE potential supervisor from our list of academic staff, https://www.qub.ac.uk/schools/mdbs/Research/find-a-phd-supervisor/, and send an email containing: (1) a brief CV (1-2 pages maximum), (2) a concise statement of motivation including research interests, (3) source of funding, and (4) intended start date.
Our academic staff welcome approaches from prospective students and are happy to develop research proposals of mutual interest. Often this process will involve an informal face-to-face meeting (in person or via teleconferencing) prior to an invitation to submit a formal application. If you have difficulty identifying or contacting an appropriate supervisor, please contact Professor AJ McKnight, Director of Postgraduate Research, firstname.lastname@example.org, or the School Postgraduate Office, email@example.com, who will be happy to help.
Postgraduate students in the School of Medicine, Dentistry and Biomedical Sciences will receive ongoing training in scientific writing, presentation and critical analysis as the basis for a research career. The School supports and challenges its postgraduate research students through robust annual progress review, requiring satisfactory assessment of written work, symposia presentations, supervisor reports and panel interview, the success of which is evidenced by its excellent completion rates. At the end of their postgraduate research training period, students are required to submit a thesis of their research of appropriate length and content which is assessed by oral examination conducted by an external and internal examiner.
Postgraduate research students in the School of Medicine, Dentistry and Biomedical Sciences receive feedback on their written and oral work throughout the period of registration for their degree. This may be both formal and informal and is provided regularly by their supervisors, peers, academic/postdoctoral colleagues, and annual progress review panel.
Postgraduate students in the School of Medicine, Dentistry and Biomedical Sciences benefit from world-class infrastructure and academic faculty and are highly valued as a central and critical component of its research strategy. All students will have access to shared laboratory and office space as required by their research project.https://www.qub.ac.uk/schools/mdbs/
The minimum academic requirement for admission to a research degree programme is normally an Upper Second Class Honours degree from a UK or ROI HE provider, or an equivalent qualification acceptable to the University. Further information can be obtained by contacting the School.
For information on international qualification equivalents, please check the specific information for your country.
English Language Requirements
Evidence of an IELTS* score of 6.5, with not less than 5.5 in any component, or an equivalent qualification acceptable to the University is required. *Taken within the last 2 years.
International students wishing to apply to Queen's University Belfast (and for whom English is not their first language), must be able to demonstrate their proficiency in English in order to benefit fully from their course of study or research. Non-EEA nationals must also satisfy UK Visas and Immigration (UKVI) immigration requirements for English language for visa purposes.
For more information on English Language requirements for EEA and non-EEA nationals see: www.qub.ac.uk/EnglishLanguageReqs.
If you need to improve your English language skills before you enter this degree programme, INTO Queen's University Belfast offers a range of English language courses. These intensive and flexible courses are designed to improve your English ability for admission to this degree.
|Northern Ireland (NI) 1||£4,596|
|Republic of Ireland (ROI) 2||£4,596|
|England, Scotland or Wales (GB) 1||£4,596|
|EU Other 3||£23,850|
1 EU citizens in the EU Settlement Scheme, with settled or pre-settled status, are expected to be charged the NI or GB tuition fee based on where they are ordinarily resident, however this is provisional and subject to the publication of the Northern Ireland Assembly Student Fees Regulations. Students who are ROI nationals resident in GB are expected to be charged the GB fee, however this is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.
2 It is expected that EU students who are ROI nationals resident in ROI will be eligible for NI tuition fees. The tuition fee set out above is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.
3 EU Other students (excludes Republic of Ireland nationals living in GB, NI or ROI) are charged tuition fees in line with international fees.
All tuition fees quoted are for the academic year 2021-22, and relate to a single year of study unless stated otherwise. Tuition fees will be subject to an annual inflationary increase, unless explicitly stated otherwise.
More information on postgraduate tuition fees.
Additional course costs
Depending on the programme of study, there may also be other extra costs which are not covered by tuition fees, which students will need to consider when planning their studies . Students can borrow books and access online learning resources from any Queen's library. If students wish to purchase recommended texts, rather than borrow them from the University Library, prices per text can range from £30 to £100. Students should also budget between £30 to £100 per year for photocopying, memory sticks and printing charges. Students may wish to consider purchasing an electronic device; costs will vary depending on the specification of the model chosen. There are also additional charges for graduation ceremonies, and library fines. In undertaking a research project students may incur costs associated with transport and/or materials, and there will also be additional costs for printing and binding the thesis. There may also be individually tailored research project expenses and students should consult directly with the School for further information.
Some research programmes incur an additional annual charge on top of the tuition fees, often referred to as a bench fee. Bench fees are charged when a programme (or a specific project) incurs extra costs such as those involved with specialist laboratory or field work. If you are required to pay bench fees they will be detailed on your offer letter. If you have any questions about Bench Fees these should be raised with your School at the application stage. Please note that, if you are being funded you will need to ensure your sponsor is aware of and has agreed to fund these additional costs before accepting your place.
How do I fund my study?1.PhD Opportunities
Find PhD opportunities and funded studentships by subject area.2.Funded Doctoral Training Programmes
We offer numerous opportunities for funded doctoral study in a world-class research environment. Our centres and partnerships, aim to seek out and nurture outstanding postgraduate research students, and provide targeted training and skills development.3.PhD loans
The Government offers doctoral loans of up to £26,445 for PhDs and equivalent postgraduate research programmes for English- or Welsh-resident UK and EU students.4.International Scholarships
Information on Postgraduate Research scholarships for international students.
Funding and Scholarships
The Funding & Scholarship Finder helps prospective and current students find funding to help cover costs towards a whole range of study related expenses.
How to Apply
Apply using our online Postgraduate Applications Portal and follow the step-by-step instructions on how to apply.
Find a supervisor
If you're interested in a particular project, we suggest you contact the relevant academic before you apply, to introduce yourself and ask questions.
To find a potential supervisor aligned with your area of interest, or if you are unsure of who to contact, look through the staff profiles linked here.
You might be asked to provide a short outline of your proposal to help us identify potential supervisors.