MRC AIM DTP Studentships

Qualification: PhD

Departments: Cardiovascular Sciences Cancer Research Centre School of Chemistry Genetics Molecular and Cell Biology Neuroscience Psychology and Behaviour

Application deadline: 9th January 2022

Start date: 26th September 2022

Overview

MRC AIM is a Doctoral Training Programme (DTP) funded by the MRC between three academic partners – Universities of Birmingham, Nottingham, and Leicester.

Research projects within the DTP are focused around the theme of Complex Disease, which allows doctoral students to benefit from a diverse range of projects and skills within the cohort, stimulating students to think ‘outside the box’ and perform innovative, world-leading research.

Applicant Q&A session

The DTP Leads are holding a Q&A session for prospective candidates interested in applying to the DTP on Thursday 9 December 10:00 – 11:00 GMT via Zoom.  If you are thinking of submitting an application(s) to the DTP, you are invited and encouraged to attend the session.  Please register for the event by clicking on the link here before 16:00 GMT on Wednesday 8 December.  As well as having the opportunity to ask questions, the session will also provide information on the application process as well as more information about the AIM DTP.

Projects for September 2022

The University of Leicester projects are listed below. Once you have made your choice please refer to the How to Apply section and submit your application forms before the deadline of Sunday 9th January 2022.

Training

Available training is likely to include the following although this is not a comprehensive list and is subject to change:

  • Communicating science to diverse audiences
  • Scientific writing
  • Industry networking sessions
  • Careers beyond academia sessions
  • Good research practice, reproducibility and FAIR data use
  • Ethics in research
  • Advanced research taster sessions
  • Statistics and quantitative methods in research
  • Mental health awareness and resilience
  • Coping with unpredictability in research
  • Team-building and leadership

Industrial Partners

A PhD opens the door for a range of research-related careers in both academic and industry settings. The DTP offers PhD projects that are co-led by academic/industry collaborations (iCASE studentships) as well as opportunities for students to undertake placements that give them a taste of working in the biomedical industry sector. We have a close relationship with two pharmaceutical companies, AstraZeneca and UCBPharma, who will provide all DTP students with valuable knowledge and insight into the sector, as well as ensuring that our comprehensive training programme equips our students with the necessary skills for a career outside of academia.

Doctoral Training Partnerships

Doctoral Training Partnerships (DTPs) and Centres for Doctoral Training (CDTs) are multi-disciplinary, multi-institutional schemes designed to support the training of the next generation of world-class researchers. The University of Leicester is a lead partner in four DTPs/CDTs through which we can offer funded PhD studentships in a wide range of research areas. 

Studentships are available to highly motivated and qualified applicants and provide a generous support package usually including a full fee waiver, annual stipend, and research training support grant. Studentships are in most cases offered early in the year for September start. Enquiries outside of the main application periods are welcomed.

Projects for September 2022

Biophysical models of cohesin-mediated 3D genome folding and its role in DNA-based processes

Professor Daniel Panne (University of Leicester) and Dr Peijun Zhang (Research Complex at Harwell; RCaH)

It has been proposed that DNA folding by a process called ‘loop extrusion’ by cohesin is a central organising principle of genome conformation. The hypothesis is that loop extrusion reels in genomic DNA into loops, a process which ‘individualises’ chromatin fibres and brings distant loci into proximity. The resulting higher-order packing of chromosomal DNA is thought to have important structural and regulatory consequences for chromosome segregation and other DNA-based processes.

In this project we will address how a key control factor controls the ‘loop extrusion’ process by cohesin. You will determine the underlying molecular mechanism using structural biology (cryoEM/Xray) and biochemical methods. To visualise loop extrusion in cells we will use our established cryoFIB-SEM pipeline to image the conformation of chromosomes under native conditions and at high resolution. These methods will allow you to study the impact on large-scale chromosomal features at supra-molecular detail. The project will provide fundamental insights into the mechanisms that control chromosome structure in cells. We anticipate that our work may also provide insights into the aetiology of human disorders caused by dysregulation of cohesin including congenital diseases called ‘cohesinopathies’ and genetic disorders such as aneuploidies and spontaneous human abortions.

Establishing clinically relevant zebrafish animal models to study abnormal retinal development using CRISPR-Cas9 mutagenesis

Dr Mervyn Thomas (University of Leicester), Associate Professor Will Norton and Professor Ferenc Mueller

The development of CRISPR-Cas9 mutagenesis has revolutionised our ability to study human diseases and create animal models with clear translational potential. In this project, the student will use modern mutagenesis techniques to create “humanised” zebrafish models of genetic mutations that affect the visual system. We will model genetic mutations from both our local next generation sequencing studies and the 100,000 genomes project to rapidly characterise the functional impact in zebrafish. This will prioritise variants and disease genes within a clinical setting. Structural and functional characterisation of the zebrafish will be achieved using high resolution imaging techniques and state-of-the art visual behavioural and electrophysiological assays. This project brings together a supervisory team with expertise in ocular genetics, animal models, high resolution imaging, visual behavioural and functional assays across the Universities of Leicester and Birmingham. The student will be trained in application of state-of-the art techniques in each field and will be based within clinical and translational units namely, the Ulverscroft Eye Unit at Leicester and Birmingham Centre for Genome Biology.

The supervisory team have an excellent track record with PhD students including previous students winning highly commended national postgraduate awards, presenting their work at international meetings and securing competitive fellowships.

Identifying dysfunctional T-cell signatures in patients with aggressive diffuse large B cell lymphoma (DLBCL) (iCASE project)

Professor Martin JS Dyer (University of Leicester), Dr Matthew J Ahearne, Dr Sandrine Jayne, Dr Harriet S Walter, Professor Alex G Richter and Professor Duncan Baird TeloNostiX (Cardiff)

Therapies that “reawaken” and redirect the immune system have shown huge promise in patients with advanced malignancy.  “Reawakening” the immune system can be achieved using bispecific antibodies (BsAbs).  These bind to tumour cells on one arm and to normal T cells on the other, thereby creating an immune synapse which facilitates tumour destruction.  The BsAb glofitamab binds to the B cell specific CD20 and T-cell-specific CD3.  50% of lymphoma patients receiving glofitamab in early phase clinical trials entered a durable complete remission; glofitamab is the most potent CD20 antibody to date.

Nevertheless, not all patients respond and the reasons for this are not clear.  One possibility is that the T-cell functions are impaired in lymphoma patients.  Surprisingly, functions of the immune system have not been extensively characterised in patients with DLBCL.

The aims of this study are therefore to determine the nature and functions of T cell populations in DLBCL using a multiomic approach (multi-parameter flow cytometry, single cell proteomics and RNA Sequencing).  Telomere length will be determined in collaboration with TeloNostiX. These data will be integrated with whole exome sequencing data from primary tumours and will define optimal conditions for the use of BsAbs in earlier phases of treatment.

Native Mass Spectrometry Guided Optimisation of 14-3-3 Molecular Glues for Cancer Therapeutics

Dr Richard Doveston (University of Leicester) and Dr Aneika Leney

Using drugs that ‘stick’ proteins together, or ‘molecular glues’, is a potentially hugely powerful therapeutic strategy across a range of disease areas. However, molecular glues have not been exploited to anywhere near their full potential in large part because their development has been hampered by a lack of tools that tell us how they work. This project will adapt, refine and use a technique called native mass spectrometry to guide the design and optimisation of molecular glues. The native mass spectrometry approach for studying molecular glues was recently developed in our laboratories and has exciting potential for speeding up the optimisation of molecular glues. We will focus on the design and optimisation of glues that target the interactions of an important protein called 14-3-3 which plays a particularly important role in preventing and fighting cancer. Thus the project will deliver much needed novel cancer therapies which can ultimately be used to tackle hard to treat cancers or problems surrounding drug resistance. This is a highly interdisciplinary project that will provide world-class training in native mass spectrometry techniques, chemical biology and drug design.

Targeting Staphylococcus aureus copper resistance as a novel antimicrobial strategy in skin infection models

Professor Julie Morrissey (University of Leicester), Professor Kim Hardie, Professor Joan Geoghegan and Dr Rian Griffiths

Staphylococcus aureus uses host antimicrobial copper as a regulatory signal to alter gene expression to promote colonisation. The proposed project will target this response to identify new antimicrobials to treat serious S. aureus skin infection. MRSA are a cause of severe soft skin tissue infections that pose a major economic and clinical burden. The aim of this interdisciplinary project is to build on our expertise of S. aureus copper resistance, novel skin infection models and innovative imaging and mass spectrometry analysis to test our hypothesis that copper resistance plays an important role in S. aureus skin infections and identify novel antimicrobials. The objectives are to:

  1. Characterise the distribution of metal and bacteria, and phagocyte responses in skin infection models.
  2. Determine whether CuR alters progression to chronic infections in skin infection models.
  3. Map metabolites in skin infection models to identify the metabolic status of the host and pathogen.
  4. Identify novel S. aureus antimicrobials by screening the 80k compound library.

The student will benefit from expertise spanning three universities: training in microbiology, highly innovative skin infection models, and imaging approaches including super resolution fluorescent and scanning electron microscopy, mass spectrometry and high throughput phenotyping to identify novel antimicrobials.

Three dimensional characterisation of regional cardiac electrophysiological changes underlying lethal arrhythmia mechanisms in heart failure

Professor G André Ng (University of Leicester), Dr Reshma Chauhan, Dr Davor Pavlovic and Dr Chris O’Shea

Sudden Cardiac Death (SCD) is a major unsolved clinical problem claiming 100,000 lives in the UK each year. The majority of these deaths are due to lethal heart rhythm disturbances or arrhythmias such as Ventricular Fibrillation (VF). Abnormal function of the autonomic nervous system predisposes heart disease patients to cardiac arrhythmia. However, due to an incomplete understanding on the underlying mechanisms, there is no effective treatment or preventative therapy. A better understanding of autonomic function and cardiac electrophysiology is required for the progression of clinical interventions.

The aim of this project will be to investigate the changes in cardiac electrophysiology across the heart surface as a result of heart failure and autonomic dysfunction. This will be explored using a custom-built panoramic optical mapping system, which gives a 360° view of the heart and can record novel 3D cardiac electrophysiology data. This project will enable the development of valuable technical skills such as surgical skills, experience with in vitro preparations, advanced optical mapping techniques and experience in generating a clinically relevant model of heart failure. This project will also provide the opportunity to explore a key research area, use innovate new software and produce novel data that will support the development new clinical therapeutics.

Understanding the role of phages in the spread of antibiotic resistance and virulence genes in Enterococci

Dr Andrew Millard and Professor Willem van Schaik

Enteroccoci are one of the leading causes of hospital-acquired infections and are becoming increasingly difficult to treat due to increasing antimicrobial resistance. An understudied area of research is how bacteriophages (viruses that infect bacteria) may play an important role in the transfer of antibiotic resistance genes. It has long been known phage can mediate horizontal gene transfer; however, the recent discovery of lateral transduction, where phage mediate horizontal gene transfer, occurred at frequencies far higher than previously known. Additionally, there is now increasing evidence that prophages (phages that integrate into a bacterial genome) harbour antibiotic resistance genes and virulence genes within their genome.

This project will focus on understanding the role of phages in mediating horizontal gene transfer in Enterococcus. The project brings together expertise from two complementary research groups, offering the opportunity for training in culturing of facultative anaerobes, phage isolation, genomic analysis and development of an in vivo model system in Galleria mellonella to study lateral gene transfer.

Funding

Funding

 The competition funding provides students with:

  • 4 years of  stipend at UKRI rates
  • 4 years of tuition fees at UK fee rates  (Plus one award of a full overseas fee waiver to a international applicant)*
  • RTSG
  • Budget to help with the cost of purchasing a laptop

*It may be possible to fund further exceptional international candidates but this will be limited to stipend and UK tuition fees. If awarded applicants must be able to demonstrate they can fund the difference between UK and International fees for the duration of their studies.

Entry requirements

Entry requirements

Academic requirements
Minimum qualifications and experience to undertake a research degree are detailed in the QAA UK Quality for Higher Education. For some subject areas, there is also an expectation that an individual will have undertaken a Masters qualification before beginning a doctoral programme. Candidates should possess the relevant qualifications and/or experience to demonstrate a capability to undertake a doctorate, which will be assessed during the recruitment process. 

More details can be found on the MRC website

Evidence of English Language proficiency may be required 

Informal enquiries

Informal enquiries

Project / Funding Enquiries: mrc-aim@contacts.bham.ac.uk

Application enquiries to mrc-aim@contacts.bham.ac.uk

How to apply

How to apply

How to apply for MRC AIM projects

Select your project and follow the guidelines on the AIM website

Completed applications and references to be submitted to mrc-aim@contacts.bham.ac.uk before the deadline of Sunday 9 January 2022

Interviews to be held 1st, 3rd and 4th March 2022 via Zoom. You will need to ensure that you are available on these days for interview if you are shortlisted.

You can also refer to PhD Opportunities on the AIM website

Eligibility

Eligibility

The MRC AIM studentships are available to UK and international* applicants who meet the academic criteria. 

Full details on eligibility, including residence requirements can be found on the Full Eligibility Criteria or on the UKRI website

*funding restrictions apply to international applicants