Manchester Biomedical Research Centre PhD studentships
The NIHR Manchester Biomedical Research Centre (BRC) connects world-leading researchers based at The University of Manchester and three NHS Trusts in Greater Manchester, with a joint vision to drive forward the transformation of scientific breakthroughs into life-saving treatments and care for patients.
Please formally apply by sending your CV, name and contact details for two referees and a covering letter (500 - 750 words max) indicating your first choice project (you may apply for a maximum of two) and explaining why you want to apply for the project(s) advertised. Please also comment on your suitability for the post, giving an overview of your relevant experience and training. Applications should be sent to MCRCtraining@manchester.ac.uk
When applications have closed, the Supervisor for each project will review all submissions. Supervisor contact details are included in the project summary details and you are strongly encouraged to contact the Supervisor for an informal discussion at this stage. Alternatively you will be sent an email to inform you of the result of the application and next steps.
Please note that references will only be taken up for those candidates invited for face-to-face interview.
The closing date for applications for projects beginning in 2018 is 1 December 2017. Any applications received after the deadline date will not be considered.
Interviews will take place on Friday 12 January 2018 at the Manchester Cancer Research Centre building, 555 Wilmslow Road, M20 4GJ. All shortlisted candidates will be interviewed either face to face or by Skype (only if a Visa is required to travel and by exception).
Interview Process and What to Expect on the Day
Formal interviews will be conducted by our interview panel (exact times will be confirmed by email if you are selected) and will consist of:
- A presentation by the applicant
- A discussion with panel
- A question and answer session with panel
Prior to the interview day, a full itinerary will be sent to you confirming further details about the interview process including information about additional activities that may take place on the day, as well as practical information on getting to the interview location. Please ensure that you provide full contact details in your CV including an up to date email address and telephone number (preferably a mobile number) for correspondence.
Projects for 2018
Project title: Developing tumour-specific immune signature as prognostic biomarker of relapse after radiotherapy in bladder and prostate cancers
- Lead supervisor: Professor Tim Illidge
- Co-supervisor(s): Professor Catharine West, Dr Debayan Mukherjee
- Type: Non-clinical studentship
Radiotherapy (RT) is often used as the primary curative treatment for localised prostate and bladder cancer; however not all patients respond well to treatment and many relapse locally and/or with aggressive metastatic disease. In addition to the direct cytoreductive effect of RT, ionising radiation can alter the immune context of the tumour microenvironment (TME), and the nature of these immune infiltrating cells in the TME is increasingly recognised to influence the clinical outcome. Furthermore hypoxia is a common feature of solid tumours and associated with a poor prognosis following RT. Whilst hypoxia and an immune suppressor phenotype are independently prognostic, the potential link between the two adverse prognostic factors in different cancers is poorly understood. As RT is increasingly used within multi-modality therapies, and there is interest in combining it with both hypoxia-modifying agents and immunotherapy, there is a need to better understand the interplay between the two factors.
This multidisciplinary project aims to: (1) identify immune regulatory genes expressed by tumour cells after exposure to radiation and hypoxia; (2) investigate the type of immune suppressor cells in the TME of human tumours and relationships with hypoxia; (3) undertake large scale transcriptomic analysis to derive immune gene signatures that provide independent prognostic information and can be combined with existing hypoxia signatures, as part of multiplexed tumour-type-specific profiling for future biomarker driven trials.
This project will be undertaken in laboratories with world class expertise in tumour immunology and radiobiology. The project will involve working with clinical and non-clinical scientists and will require learning state-of-the-art techniques in immunology, high content transcriptomics, analysis of large data sets, automated multiplex immunohistochemistry, and advanced imaging.
Please contact firstname.lastname@example.org for more information.
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Project title: Proteomic profiling in cancer patients undergoing radiotherapy
- Lead supervisor: Professor Catharine West
- Co-supervisor(s): Dr Ananya Choudhury, Professor Martin Humphries, Professor Tony Whetton, Dr Jonathan Humphries
- Type: Non-clinical studentship
The field of mass spectrometry-based proteomics has enormous potential for systems- level analysis of biology to discover new biomarkers and therapeutic targets in oncology. High throughput and resolution proteomic profiling has become increasing feasible and Manchester has built the largest clinical proteomics facility in Europe to drive the identification, validation and incorporation into clinical practice of protein biomarkers. Radiotherapy related research is a strategic priority for the Manchester Cancer Research Centre and was a theme in the successful Biomedical Research Centre (BRC) bid. A remit of the BRC award is to forge new interdisciplinary collaborations to drive innovations and one aim of the radiotherapy theme was to build on current expertise in hypoxia biomarker research to establish a new inter- disciplinary collaboration with basic research strength in life sciences to increase understanding of how hypoxia impacts on cell adhesion/invasion and how it might be targeted therapeutically. Hypoxia is a feature of solid tumours than confers a poor prognosis irrespective of treatment. Hypoxia promotes invasion and metastasis formation and up-regulates genes involved in extracellular matrix homeostasis that maintain and distribute growth factors and chemotactic signals to promote metastasis formation. Given the importance of the hypoxia as an adverse prognostic feature of cancer, increased understanding of how it promotes cancer spread could be exploited to develop new biomarkers and in the long-term underpin the development of new therapeutic approaches to reduce the formation of metastasis. A question of interest that will be addressed in the PhD is: can a pan tumour proteomic matrisome (structural components of the extracellular matrix including proteins that interact or modify it) signature be derived that reflects the hypoxia phenotype associated with transcriptomic signatures?
Please contact email@example.com for more information.
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Project title: Improving the precision of lung cancer risk prediction
- Lead supervisor: Dr Phil Crosbie
- Co-supervisor(s): Professor Gareth Evans, Dr Miriam Smith, Dr Emma Crosbie
- Type: Non-clinical studentship
Background: Lung cancer (LC) is the most common cause of cancer related death. The main determinant of risk is chronic exposure to tobacco smoke. This risk is modified by other factors e.g. COPD, but may also be modified by genetic factors including those related to carcinogen metabolism and DNA repair; which may be identified through analysis of single nucleotide polymorphisms (SNPs). Targeted screening of ‘high-risk’ smokers reduces LC specific mortality; but current strategies use clinical measures alone to estimate risk. In this study, the student will investigate the additional benefit of adding a genetic score to LC risk prediction tools. More precise risk prediction could improve the efficacy of screening and thereby improve outcomes.
Objective: (1) To perform a systematic review to identify SNPs that have previously shown promise in LC; (2) to design and perform SNP array genotyping in a discovery cohort of LC cases and controls; (3) to validate and test our LC risk prediction model in a population undergoing lung cancer screening.
Methods: First, a systematic review will be performed to identify published studies of SNPs and LC risk. Where possible, the student will perform a meta-analysis to establish a priori which SNPs are most important. SNPs with sufficiently robust evidence will be taken forward. Next, s/he will custom design a Sequenom MassARRAY iPLEX assay based on these data. Using 15-18 SNPs, s/he will genotype patients with histologically-proven LC (n=700) and age-matched controls (n=700) in a case-control study of ever smokers, whose blood samples have already been banked. Finally, the student will incorporate a ‘genetic risk score’ to LC risk prediction tools and model performance in a validation cohort, taken from a targeted lung cancer screening programme. S/he will test for associations between the factors to determine whether they are strongly correlated or independently predictive of risk.
Please contact firstname.lastname@example.org for more information.
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