Jobs
  

MRC AIM Doctoral Training Partnership

Reference
MED1605
Closing Date
Sunday, 9th January 2022
Department
Medicine

The AIM (Advanced Inter-Disciplinary Models) DTP is funded by the Medical Research Council 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 Institutions which are now open for a September 2022 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.

Application deadline: The deadline for submitting applications is Sunday 9 January 2022. Please ensure that your application is submitted with all required documentation as incomplete applications will not be considered.

Interviews: Interviews will take place Tuesday 1, Thursday 3 and Friday 4 March 2022 and will be held via Zoom.  You will need to ensure that you are available on these days for interview if you are shortlisted.

Academic requirement: Minimum qualifications and experience to undertake a research degree are detailed in the QAA UK Quality Code 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.

Applicant Q&A session: The DTP Leads are holding an information / 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.

How to apply: Please complete the AIM application form one and application form two as well as the AIM equal opportunities form. These can be downloaded at https://more.bham.ac.uk/mrc-aim/phd-opportunities/ . You will need to ensure that your referees complete the AIM referee form and submit this to mrc-aim@contacts.bham.ac.uk in support of your application.

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

Due to stipulations from the funders, recruitment for international candidates to the DTP is capped at 30% of the whole cohort.

Projects open for application in the School of Medicine:

Development of an Advanced Age-Related Cellular Model to Improve Understanding of Neurodegenerative Diseases

Dr Mattéa Finelli, Dr Veeren Chauhan, Dr David Bassett and Dr Salvador Macip

Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are age-related disorders, caused by the death of neurons in the brain and spinal column. They affect >60 million people worldwide and there are currently no effective treatments for these diseases.

Stem cell-derived cellular models are powerful in vitro tools used in biomedical research and pharmaceutical industry to study disease mechanisms and find new drugs. However, most commonly-used stem cell-derived cellular models do not mimic the features associated with aging, which is not ideal for studying age-related disorders such as neurodegenerative diseases.

Therefore, this collaborative project between the Universities of Nottingham, Birmingham and Leicester aims to:

• Generate a cellular model for ‘aged’ neurons

• Identify markers characteristic of ‘aged’ neurons

• Explore the role of key regulators of neuronal aging

Longer-term, the cellular model that will be developed in this project could be used to find and test new drugs for neurodegenerative diseases and potentially other age-related neurological conditions. The PhD student on this project will learn advanced techniques in stem cell technology, bioengineering, proteomics, the use of animal models and will acquire quantitative and interdisciplinary skills, and expertise in whole organism biology.

Identifying the pathways underlying multi-organ fibrosis through clinical analyses and computational modelling of dietary factors and gut microbiota

Assistant Professor Jane Grove, Dr Jan-Ulrich Kreft, Dr Robert Scott and Professor Guruprasad Aithal

People are increasingly developing fibrosis (scarring) in multiple organs (liver, pancreas, intestine) resulting in common, severe diseases which reduce life-span and quality-of-life. There is an urgent need to develop tests to identify multi-organ fibrosis and treatments to slow or reverse its progression. This project aims to discover how changes in patients’ gut microbe population are linked to foods consumed and how we can identify people susceptible to developing scarring and severe disease.

This research is connected to a large clinical study in which samples, lifestyle and medical information will be collected from patients at Nottingham Biomedical Research Centre (including using new MRI methods to reveal features of the intestine). It involves working as part of an internationally-recognised, diverse, multi-disciplinary and enthusiastic research team.

The studentship will specifically involve metagenomics to identify the gut microbe composition, and fecal metabolomic, bioinformatic analyses to discover distinct signatures of fibrotic disease. Advanced computational methods established in Birmingham (integrating patient data) will be used to develop models of disease mechanisms. These will reveal possible impacts on different organs and effects of treatments. Overall, biomarkers of progressive scarring and potential treatments targets will be identified, as well as specific interventions to tackle the problem.

iCASE:

Self-assembling matrixes to recreate the colorectal tumour niche (iCASE project)

Dr Paloma Ordóñez-Morán, Professor Alvaro Mata.  Industry Supervisor: Carmen Pin PhD AstraZeneca, Cambridge UK

Patient-derived in vivo models of human cancer have become a reality, yet their turnaround time is inadequate for clinical applications. Therefore, tailored ex vivo models that faithfully recapitulate in vivo tumour biology are urgently needed. This project aims to optimize an in vitro 3D organoid culture that would enable the study of the complexity of colorectal cancer and the effectiveness to drug response. To that end, we will use patient-derived organoids to optimize a novel peptide-based assembly platform that will represent a step-change in how putative anticancer drugs can be tested in vitro. In the long-term the outcome of this project may help to improve cancer patient’s survival.

Unravelling drug-gene-phenotype interactions in complex cardiovascular diseases (iCASE)

Professor Chris Denning, Dr Davor Pavlovic, Mattea Finelli, Amy Pointon and Will Stebbeds at GSK UK

Globally, cardiovascular disease is the leading cause of death, with underlying genetic mutations, comorbidities and drug-induced off-target cardiotoxicity being especially troublesome. Inappropriate testing models belie these issues. The top 200 drugs account for 66.6% of the 4.3bn prescriptions in the USA/pa. Yet, 81 are black boxed, 82 carry cardiovascular adverse drug reaction warnings and 1 in 7 licensed drugs deemed efficacious in phase III trials are withdrawn from the market.

This collaborative project is joint between Universities of Nottingham and Birmingham, AstraZeneca and GlaxoSmithKline. Collective interdisciplinary experience spans human induced pluripotent stem cells (hiPSCs), differentiation to cardiovascular linages, molecular/functional phenotyping, robotics, pharmacology, transcriptomics and bioinformatics/coding/AI. Our published work pioneered CRISPR gene editing in hiPSC to create variants that cause hypertrophic cardiomyopathy (HCM), a complex heterogeneous disease associated with considerable morbidity and mortality.

Diverse skillsets and training will be combined to complete 3 objectives, aimed at future tailoring and translating drug therapy to patient genetics:

  • Establish baseline structure/functional readouts for healthy and diseased (hypertrophic cardiomyopathy; HCM) microtissues comprising cardiovascular lineages derived from human induced pluripotent stem cells (hiPSCs)
  • Quantify changes in microtissue structure/function challenged with patient-relevant drugs
  • Use omics/AI approaches for mechanistic insight and pathways information to refine drug use.