MRC AIM Doctoral Training Partnership: School of Medicine

University of Nottingham

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Medicine
Location:  UK Other
Closing Date:  Friday 12 January 2024
Reference:  MED1974

MRC AIM Doctoral Training Partnership

The AIM (Advanced Inter-Disciplinary Models) DTP is funded by the MRC between three Partners – the Universities of Birmingham, Leicester and Nottingham – and three more Associate Partners – the Research Complex at Harwell, Mary Lyon Centre and Rosalind Franklin Institute. We have a range of exciting and diverse PhD 4-year projects at all 3 partner Institutions which are now open for a September 2024 start and those available at The University of Nottingham are detailed below.

Projects with an industry partner (iCASE projects) offer a unique opportunity to undertake translational research and come with a mandatory placement requirement and an enhanced stipend.

Full information about funding of these projects and application details, including application form, plus Equality, diversity and inclusion form are available at https://more.bham.ac.uk/mrc-aim/phd-opportunities/ .

Application deadline

The deadline for submitting applications is Friday, 12 January 2024. Please ensure that your application is submitted with all required documentation by the above deadline as incomplete applications will not be considered. See full details at the “how to apply” section below. After the closing date, the project supervisors will review all applications submitted for their project and shortlist a maximum of two candidates for interview.

Shortlisted applicants will be contacted by 9 February 2024 via email. If applicants don’t receive an email by this date, then their application has not been shortlisted and they will not be invited for interview. Unfortunately, due to the number of applications the DTP receives, it will not be possible to provide feedback on unsuccessful applications.

Interviews

Interviews will take place during the week commencing 26 February and will be held via Zoom.   Please ensure you are available for the whole week as we are unable to offer any alternative interview dates/times.

We strongly encourage you to contact the supervisor(s) of the project in which you are interested before submitting an application. 

As stipulated by the funders, recruitment for International candidates to the DTP is capped at 30% of the whole cohort.

Academic requirement

Applicants must hold, or be about to obtain, a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant subject. A master’s qualification in a related area could be beneficial, as could additional relevant research experience. 

More details can be found on the MRC website.

How to apply

Applications should include:

  • A completed application form
  • A CV consisting of no more than 2 sides of A4
  • A transcript of module marks
  • Completed ED&I form.

Please submit your application for University of Nottingham projects to [email protected] .

What happens after interview?

Candidates who are ranked highest at interview will be offered a place on the DTP and will be recommended for the PhD position. Successful candidates will then be sent details of how to make the formal application at the project host institution and will be subject to standard admissions checks which is standard procedure. The host institution admissions team will then send out formal offer letters and details of how to complete the registration process. The DTP Funding Team will send out formal funding award letters.

Projects open for application

School of Medicine

Project Title Leveraging genetics to identify drug targets for respiratory disease

Supervisors Professor Ian Sayers, [email protected] , Dr Robert Hall (UoN), Professor Louise Wain (Leicester), Dr Nick Shrine (Leicester)

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We have made significant advances in identifying genetic variants that increase the risk of lung function impairment and chronic obstructive pulmonary disease (COPD), including recently 26 genetic variants that are potentially deleterious to protein structure/function. 

The aim of this PhD studentship is to focus to these potential deleterious coding variants/genes and use a combination of genetic epidemiology, molecular biology, primary cell/tissue models to provide insight into disease mechanisms and identify potential therapeutic opportunities.  

We will investigate predictive models for the impact of variants on protein structure. Candidate genes will be prioritised for functional work based on predicted protein alterations, single cell and spatial gene and protein expression profiling and scope for targeting by drugs. We will prioritise a subset of candidates for functional evaluation in a series of in vitro models ranging in complexity including primary cell, multicellular, lung tissue models in combination with genome editing to understand the role of the proteins and variant proteins in cell homeostasis and initiate studies to target altered mechanisms. 

This studentship is part of a collaboration involving the Universities of Nottingham, Leicester, and Cambridge and will include training and skills development in genetic epidemiology, bioinformatics, genome editing, molecular biology, cell biology and imaging.

Project Title: Is metabolic reprogramming the key to treatment failure in aggressive brain tumours? A multi-nuclear in vivo ultrahigh-field MRI approach.

Supervisors: Dorothee Auer, [email protected] , Richard Bowtell (Physics & Astronomy, UoN), Peter Harvey (UoN), Martin Wilson (UoB)

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Glioblastoma is the deadliest brain cancer with poor survival rates despite improved understanding of its genetic causes; novel treatments in lymphomas offer survival benefits for some people with lymphomas, but when treatments fail, the median survival time is ~5 months. One reason for these poor treatment responses is the complex way in which cancer cells adapt their energy production, through a process called metabolic reprogramming. A lot of current research is therefore focused on producing a better understanding of metabolic reprogramming, so as to inform the development of effective treatments.

MRI is usually based on signals from hydrogen in water and fat, but it is also possible to make images based on signals from deuterium. As there is only a very small amount of naturally occurring deuterium in our bodies, after feeding someone with a compound containing deuterium the signal we detect mainly comes from ingested material. Measuring deuterium signals following ingestion of labelled glucose allows us to track metabolic processes involved in energy production in brain tissues. We have implemented this deuterium metabolic imaging (DMI) approach on our 7T scanner, and this PhD project will focus on applying DMI to understanding metabolic reprogramming in aggressive glioblastoma and lymphoma tumours.

Preliminary studies have demonstrated the feasibility of DMI, and the successful candidate will expand on this work by refining the acquisition protocol for regular clinical use across a range of MRI platforms (3T, 7T and 11.7T). The candidate will also explore the use of novel RF coils, MR sequences and other deuterated labelling molecules. This multi-disciplinary project presents an exciting opportunity to combine cutting-edge brain tumour research, MR physics and dynamic spectral analysis. The student will be supported in all these aspects by supervisors based at the Nottingham Biomedical Research Centre, The Sir Peter Mansfield Imaging Centre and The Centre for Human Brain Health.

Project Title Development of an optimised contractile strategy to improve the muscle health of older surgical cancer patients

Supervisors: Bethan Phillips, [email protected] , Leigh Breen (UoB), Jon Lund (UoN), Eleanor Jones (UoN)

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Following surgery for cancer, older patients lose significant muscle mass and function due to the physiological insult of surgery and physical inactivity in the postoperative period. These losses cause delayed recovery from surgery and return to normal activities and are associated with significant physical and psychological upset. Although exercise rehabilitation after surgery is recommended, and sometimes delivered, this does not begin until the surgical wound has healed- several weeks after surgery. Similarly, although exercise prehabilitation has shown great potential, many older adults are unable to complete this. Emerging evidence suggests that a single bout of resistance exercise (sRET) before surgery may have potential to reduce postoperative losses of muscle mass and function in older cancer patients. However, how this strategy may be optimised, including interactions with nutrition is not yet known. This PhD will use state-of-the-art mass-spectrometry and novel imaging techniques to: i) identify the best form of sRET to promote muscle anabolism during subsequent immobilisation; ii) determine the impact of adjuvant protein nutrition on sRET-induced anabolism; and iii) determine the impact of optimised sRET in older colorectal cancer patients. This project will provide the successful candidate with varied skills and experience across the translational research pathway (i.e., bench-to-bedside).

Project Title: Functionalised contact lenses for the topical delivery of cell therapies to treat chronic ocular surface inflammatory conditions

Supervisors: Laura Sidney, [email protected] , Felicity de Cogan (UoN), Anna Peacock (UoB), Darren Ting (UoN)

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Ocular surface disease is a significant cause of blindness. Current treatments relying on repeat dosing of steroids show poor levels of patient compliance. Alternative treatments such as corneal or amniotic membrane transplantation require complex surgery. This gives a clear unmet clinical need to address in this project.

In this project the student will develop a novel cell therapy using mesenchymal stromal cells applied to the eye via a modified contact lens. The cells respond to the wounded environment to deliver signalling molecules that cause anti-inflammatory action and wound healing.

The project will cover 4 main objectives: 1) Working with industrial partners to generate and characterise a contact lens functionalised with synthetic peptides to allow cell attachment; 2) Assessing the effect of the functionalised contact lens on the metabolism and phenotypes of stem cells in tissue culture; 3) Building an ex vivo inflammation model of the ocular surface; 4) Assessing the efficacy of the functionalised contact lens in the ex vivo model. It is a wet-lab project incorporating methodologies from chemistry, materials science, molecular biology, human tissue handling and high-throughput protein assays and will provide the student with training in many different translational skills.

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