We have a range of exciting and diverse PhD projects at our 3 partner University institutions of Birmingham, Leicester and Nottingham which are now open for application for a September 2025 start.
Projects with an industry partner (iCASE projects) offer a unique opportunity to undertake translational research.
How to apply
Please complete the AIM DTP application form, including a 2 page CV and 1 page screenshot confirming you have submitted the anonymous Equality, Diversity and Inclusion (ED&I) form before the deadline of midday (GMT) Friday 10 January 2025.
Complete applications should not exceed 7 pages and should include the following to be submitted as 1 document totalling no more than 7 pages:
- A completed application form of no more than 4 pages. Application forms should be formatted as follows: Arial font, point 11, single space, “normal” margins (2.54cm all round)
- a CV consisting of no more than 2 sides of A4 and formatted as above
- A 1 page screenshot of the thank you message confirming that you have completed the ED&I form
Applicants can apply for a maximum of 3 projects although there is no expectation to apply for more than 1. Please ensure you complete a separate application for each project and submit it to the host institution where the project lead supervisor is based.
We strongly encourage you to contact the supervisor(s) of the project(s) you are interested in before applying. Supervisor(s) are aware that applicants may approach them about their project and welcome the opportunity of discussing the project with applicants.
Please ensure you complete the online ED&I form. The form is anonymous and responses on the form have no reflection on whether an applicant will be shortlisted for interview. Applicants only need to complete the ED&I form once regardless of how many applications they submit. Applicants will need to take a screenshot of the thank you message once the form has been completed and submit the screenshot with the rest of the application documentation.
You will need to submit your application to the host institution of the project lead supervisor.
Birmingham applications to be submitted to mrc-aim@contacts.bham.ac.uk
Leicester applications to be submitted to aimphd@leicester.ac.uk
Nottingham applications to be submitted to ra-dtp-funding@nottingham.ac.uk
The application deadline is midday (GMT) Friday 10 January 2025. Applications which exceed 7 pages or are submitted late will not be considered and will not be responded to.
Residency requirement
We welcome applications from home and international applicants. Due to stipulations from the funders, recruitment for international applicants 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
Applicant webinars
The DTP Leads are holding two applicant webinars for prospective applicants interested in applying to the DTP. The first will be on Friday 6 December 2024 at 12:00 GMT and second on Monday 9 December 2024 at 18:00 GMT. Both sessions will last no longer than 1 hour and will be held via Zoom. If you are thinking of applying to the DTP, you are encouraged to attend one of these sessions.
If you are interested in attending the webinar on Friday 6 December please register here You will then be set an email from Zoom with details of how to join on the day.
If you are interested in attending the webinar on Monday 9 December please register here You will then be sent an email from Zoom with details of how to join on the day.
What happens after you have submitted your application?
After the closing date, midday (GMT) Friday 10 January 2025, the project supervisors will review all applications submitted for their project and shortlist a maximum of two applicants for interview.
Shortlisted applicants will be contacted by 14 February 2025 via email. Please do not email to check the status of your application. If you don’t receive an email by 14 February 2025 then we are afraid that your application has not been shortlisted and you will not be invited for interview. Unfortunately, due to the number of applications the DTP receives, we will not be able to provide feedback on unsuccessful applications. For those applicants who aren’t shortlisted, we would like to thank you for your interest in the DTP and wish you well for your future career.
Shortlisted applicants will then be invited for interview during the week commencing 24 February 2025. Please ensure you are available for the whole week as if you are invited for interview, we are unable to offer any alternative interview dates/times.
Applicants who are ranked highest at interview will be offered a place on the DTP and will be recommended for the PhD position. Successful applicants 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 online registration process.
Projects open for application are listed below.
Prof Ferenc Mueller (UoB), Prof Dov Stekel (UoN) and Dr Andrew Beggs (UoB)
Global changes in transcriptional regulation and RNA metabolism are crucial features of cancer development and are part of the adaptive process facilitating cancer growth and survival. We recently discovered how the core promoter of genes is a source of transcript variation which defines transcript identity and post-transcriptional messenger RNA fates (stability and translation), which is particularly pronounced during tumourigenesis. We have discovered a previously unappreciated selective regulation of transcription start site choice, i.e. the nucleotide position where Polymerase II starts production of mRNAs. This initiation site choice defines mRNA stability and translation upon metabolic stresses and is distinctly regulated by PI3K/Akt/mTOR and DNA damage pathways in various cancers. In this PhD project, supervised by an interdisciplinary supervisory team, we will use state of the art single cell transcriptomics technologies, in vivo imaging and system biology approaches to understand how promoters regulate metabolic-demand driven translation of mRNAs in colorectal cancer organoids. We will dissect where and in what cell states promoters regulate mRNA fate in the complex mix of cell populations in growing tumours and how they contribute to distinct transcriptomic profiles, distinct mRNA fates and how they explain varying degree of therapy responsiveness. The project will offer training in genomics data generation, next generation sequencing data analysis, culturing and in vivo high-resolution imaging of cancer organoids and in system biology tools for integrative analyses of complex genomics and 4D imaging datasets.
Dr Jack Bryant (UoN), Dr Christian Jenul (UoL), Prof Andrew Lovering (UoB) and Prof Kim Hardie (UoN)
Drug-resistant bacterial infections cause 1.27 million deaths annually and antimicrobial resistance is one of the biggest threats to global public health. To further compound this issue, no new antibiotic classes have made it to market since 1987. Therefore, there is an urgent need for discovery of new antibiotics to address this issue.
One of the most recently identified antibiotics, darobactin, was identified in the insect-killing bacteria Photorhabdus khanii. However, discovery of darobactin was hindered by the fact that the bacterium does not express the antibiotic under laboratory conditions and the trigger for expression is unknown4. This is a common problem in antibiotic and secondary metabolite discovery.
Using high-throughput transposon mutagenesis, we will develop a genome-wide, high-throughput assay for induction and identification of silent antimicrobial encoding gene clusters in Photorhabdus species. We will then identify the antimicrobials by mass spectrometry and investigate their modes of action by using a combination of high-throughput genetics, high-resolution real-time microscopy, protein purification, biochemistry and structural biology. Following this, we will assess the effects on a range of clinically relevant bacteria. This work will act as a template for the activation and identification of antimicrobials from diverse bacterial species.
Prof Dylan Owen (UoB), Dr Daniel Nieves (UoB) and Prof Andrew Cope (Clinical, King’s College London – collaborator)
Cells can be characterised on the genomic, transcriptomic or proteomic levels, however, there is a 4th, currently hidden level – how molecules are arranged within the cells. We have built a new and unique resource – a public database of protein nanoscale organisation with data acquired from single-molecule super-resolution imaging (which won the 2014 Novel Prize in Chemistry). Here, we aim to showcase the first clinical application of this new resource. We have preliminary data to show that different protein clustering on the nanoscale can impact autoimmune diseases like diabetes and arthritis. Here, we will use advanced imaging technology and the database to determine the diversity in nanoscale organisation that exists for different T cell signalling proteins in the human population. If the organisation of proteins is altered in patients suffering from autoimmune disease this could be a new way to screen for predisposition for these conditions and could also inform the development of drugs that alter protein nanoscale clustering, such as multi-meric antibody treatments. The student will therefore learn diverse and impactful methodologies in clinical immunology, data science and advanced imaging.
Dr Roberto Feuda (UoL) and Prof Beth Coyle (UoN)
Brain tumours are the leading cause of cancer-related deaths in children, with medulloblastoma being the most common malignant paediatric brain tumour. Approximately one-third of medulloblastoma patients present with metastasis at diagnosis. Group 3 (G3) subtype, predominant in infants and young children, has the lowest survival rate. Current treatments are highly aggressive and multi-modal, resulting in severe long-term consequences such as cognitive dysfunction, growth impairments, and secondary malignancies for survivors. Advancing therapies for G3 has been hindered by the limited availability of cell models that replicate the G3 tumour microenvironment and insufficient understanding of the molecular composition underlying G3 cellular architecture, which influences treatment outcomes.
The aims of this project are to:
1. Use single-cell technology to characterise the clonal landscape and regulatory networks driving G3 metastasis, chemosensitivity, and relapse in next-generation 3D preclinical tumour models.
2. Identify predictive biomarkers and gene targets for improving G3 clinical treatment.
This high-impact research opportunity bridges advanced biology and clinical medicine. The student will gain exceptional technical skills through training within a cross-disciplinary supervisory team, contributing significantly to novel therapeutic advancements. While led by the (UoL), the student will also collaborate at the (UoN) to develop 3D in-vitro tumour models.
Prof Sylwia Bujkiewicz (UoL), Dr Sam Khan (UoL), Prof Richard Riley (UoB), Dr Daniel Jackson AstraZeneca and Dr Janharpreet Singh (UoL)
This PhD project will focus on application and development of methods for evaluation of the effectiveness of cancer therapies. Modern cancer therapies are often developed for subsets of patients harbouring a particular biomarker. Therefore, clinical trials evaluating the effectiveness of cancer therapies may be small, resulting in uncertainty about the effectiveness of these therapies; for example, in improving patients’ survival. This project will investigate efficient methods for combining diverse data to improve the precision of the effectiveness estimates. In turn, it will help improve the efficiency of important decisions about which new therapies are available to patients.
You will apply a range of modern tools from biostatistics, including Bayesian analysis, and data science to evaluate cancer therapies. You will use diverse data from clinical trials, including alternative outcomes (other than survival) or different cancers, and data collected routinely in hospitals available from electronic health records.
You will benefit from an experienced supervisory team, including academics from the (UoL) and the (UoB) and experts from industry from AstraZeneca, with expertise in statistics, data science and oncology. The project will provide an opportunity to develop a range of analytical skills and gain insight into drug development processes.
Dr Tobias Bast (UoN), Prof Stephen Jackson (UoN), Dr Mairi Houlgreave (UoN), Dr Barbara Morera Maiquezv, Chief Research Officer, Neupulse and Paul Cable, CEO, Neupulse
Industrial partner Neupulse
Human brain imaging studies have linked activity of the insula brain region to action/movement control and motor tics – repetitive movements that resemble normal movements but are produced outside the normal context of these movements and are characteristic of Tourette’s.
However, such studies cannot tell us if insula activity causes tics.
In rats, the insula is similarly organised to humans and we can study tic-like movements and other Tourette’s-related behaviours. Therefore, studies in rats, where we can combine experimental brain manipulations with behavioural and neurophysiological measurements, allow us to determine if changes in insula activity cause Tourette’s-related behavioural changes.
In this project, the student will combine manipulations of insula activity in rats, using intracerebral drug microinfusions, with behavioural, electrophysiological and translational neuroimaging measurements in rats.
The project will reveal insula contributions to movement control and other behaviours relevant to Tourette’s and inform the development of new treatments, including non-invasive neuromodulation approaches. The student will spend 3 months with Neupulse, a neurotechnology start-up focusing on neuromodulation devices, where they will learn about translating and commercialising research findings. The translational neuroimaging studies in rats will be completed with our collaborators at the Leibniz Institute of Neurobiology (Magdeburg, Germany).
Associate Prof Mischa Zelzer (UoN), Dr Michael Portelli (UoL) and Associate Prof Cynthia Bosquillon (UoN)
Chronic obstructive pulmonary disease (COPD) is a terminal illness with global prevalence. This project aims to contribute to COPD management by developing new tools and understanding of COPD development caused by environmental air pollutants. Imaging of biomarkers for lung cells can be used gain insight into how individual cells and cell populations are affected by COPD; however, it is currently not possible to connect this with the microenvironment of these cells. This means that the amount and type of pollutant chemicals present around the cells is not known.
Here we will use state-of-the-art chemical imaging technologies (secondary ion mass spectrometry and electron dispersive X-ray diffraction) to image the distribution of pollutants in lung cells and tissue. We will develop computational methods to map the chemical and biological images from these samples to understand which chemicals are likely to lead to increased prevalence of COPD biomarkers.
The successful candidate will have a keen interest in chemical and biological imaging techniques and the use programming skills to perform image correlation. The candidate will learn biological sample preparation for vacuum imaging techniques, fluorescence microscopy, data handling and visualisation and a range of computational approaches, including multivariate analysis and machine learning using python.
Prof Adam P Croft (UoB), Dr Georgiana Neag (UoB) and Christoph Rau Diamond Light Source, Harwell Campus, Oxford
The Rheumatology Research Group (RRG), based at the (UoB) and the Queen Elizabeth Hospital, headed by Prof Adam Croft, is recruiting a PhD student for research into the complex relationship between synovial fibroblasts and osteocytes in inflammatory arthritis. This project is addressing a critical gap in our understanding of inflammatory bone loss by aiming to modulate the interaction between pro inflammatory fibroblasts in the joint and osteocytes in the bone cortex. You will employ cutting-edge 3D imaging microscopy techniques, including light sheet and confocal microscopy of optically cleared samples as well as synchrotron tomography, to visualise bone cellular organisation and microarchitecture with unprecedented detail. The project will also utilise state-of-the-art spatial transcriptomics to uncover molecular pathways driving osteocyte-mediated bone loss in inflammatory arthritis. You will develop expertise in advanced microscopy imaging, spatial transcriptomics, and bioinformatics, working with a multidisciplinary team led by clinician-scientist Prof Adam Croft (UoB) and collaborating with experts in 3D tissue imaging (Dr Georgiana Neag, UoB) and synchrotron tomography at the Diamond Light Source, Oxford (Christoph Rau). This research project offers a unique opportunity to contribute to the development of novel therapies aimed at preserving bone integrity in inflammatory arthritis patients. Join us in this ground-breaking endeavour to improve patient outcomes through innovative science.
Dr Richard Hopkinson (UoL) and Dr Peter Harvey (UoN)
This project aims to define how biological aldehydes regulate human metabolism. To do this, we will combine aldehyde (bio)chemistry and metabolomics using nuclear magnetic resonance (NMR) spectroscopy to identify aldehyde-sensitive metabolic enzymes and to profile aldehyde-induced metabolism changes in live human cells.
Aldehydes are chemically reactive and often toxic human metabolites but their biology is undefined. Proving that aldehydes regulate metabolism would be very exciting as it would identify new biological functions for aldehydes and would open up new ways to treat metabolic diseases.
This multidisciplinary project, which is co-supervised by the Hopkinson and Harvey Groups at the Universities of Leicester and Nottingham respectively, involves the production of human metabolic enzymes (Hopkinson), biochemical studies with metabolic enzymes and aldehydes (Hopkinson), and deuterium NMR metabolomics in human cells exposed to aldehydes and aldehyde-modulating chemical tools (Harvey). While focused on cell models, the project is linked to ongoing clinical studies at the Sir Peter Mansfield Imaging Centre in Nottingham. The PhD candidate will receive hands-on training in all the required experimental methods, including in enzymology, biochemical and biophysical methods, and in NMR and magnetic resonance imaging. Collectively, the project will confirm aldehydes as metabolic regulators and will stimulate development of new therapies.
Dr Amanda Rossiter (UoB), Associate Prof Karen Robinson (UoN), Dr Francesco Boccellato University of Oxford and Prof Marco Fritzsche University of Oxford
Personalised medicine is a promising way forward in the fight against cancer. However, for gastrointestinal cancers, we must first understand the biology underpinning host-microbiota relationships. For gastric cancer (GC), Helicobacter pylori is the main risk factor, yet in recent years, sequencing studies have revealed that the gastric microbiota is associated with GC. Dr. Rossiter’s team have recently discovered that non-H. pylori bacteria invade the gastric lamina propria during carcinogenesis. Invasive bacteria represent a novel biomarker for GC. Here, the student will use state-of-the-art human organoid technology to answer three critical questions; i) which bacteria invade the gastric lamina propria, ii) how does H. pylori facilitate invasion and iii) how does inflammation modulate invasion? Under the supervision of academics at the Universities of Birmingham, Oxford, Nottingham and the Rosalind Franklin Institute, the student will answer these questions, using a gastric mucosoid model of microbiota infection. The student will be trained in combining spatial biology techniques, such as RNAscope in situ hybridisation, and advanced three-dimensional lattice light sheet microscopy, to determine the localisation of H. pylori and non-H. pylori bacteria in this model. Ultimately, this data will inform future therapeutic options for GC, which focus on treating H. pylori and ‘invasive’ bacteria.
Dr David Guttery (UoL), Prof Huiyu Zhou (UoL) and Dr Harriet Walter (UoL)
Industrial partner Nonacus Ltd
This MRC iCASE studentship has three main aims: first, to explore the differences in genetic mutations, human papillomavirus (HPV) subtypes and microsatellite instability (MSI) that influence how under-represented populations respond to immunotherapy; second, to investigate whether the oral and gut microbiomes affect these responses; and third, to develop machine learning models to predict relapse in head and neck cancer patients using diagnostic images. This research is important and exciting because oral cancer disproportionately impacts South Asian communities, yet we lack a clear understanding of the biological factors driving these disparities. By integrating genetic, microbial, and clinical data, this project aims to provide insights that could lead to more personalized treatment strategies and improve outcomes for under-represented patients. Throughout this project, the student will gain valuable technical skills, including whole exome sequencing, targeted sequencing, microbiome analysis, and machine learning techniques. They will also spend time at Nonacus Ltd, learning to work with advanced bioinformatics tools and contributing to innovative approaches in cancer research. This multifaceted training will prepare the student for a successful career in biomedical research, with the potential to make a significant impact on public health and clinical practices.
Dr Sally Clayton, (UoB), Dr Sarah Dimeloe (UoB), Prof Andy Clark (UoB) and Dr Rahul Mahida (UoB)
Industrial partner Sitryx Therapeutics
Mitochondria are essential regulators of the immune system. The electron transport chain is the machinery of mitochondrial energy generation and is dynamically regulated by environmental cues to maintain cellular fitness. Two important cues that regulate the electron transport chain are inflammatory triggers such as infection, and a lack of oxygen availability, known as hypoxia. These cues are commonly studied separately, however during disease in the body, inflammation and hypoxia frequently occur together. This happens in the life-threatening lung disorder acute respiratory distress syndrome (ARDS), where inflammation in the lungs prevents proper oxygen delivery to the body. Therefore, to improve the prevention and treatment of conditions such as ARDS, we need to understand how the combination of these cues affects immune cells.
With the use of biochemical, molecular biology and immune profiling techniques, this project will investigate how inflammation and hypoxia interact to alter complex IV of the mitochondrial electron transport chain, and what this means for the activity of the important innate immune cell, the macrophage. Using in vivo mouse models of inflammatory lung disease and patient samples, the researcher will achieve an in-depth understanding of how these pathways impact disease and how we might harness them to benefit patients.
Dr Kevin Webb (UoN), Dr Rachel Clifford (UoN), Prof Antonino La Rocca (UoN), Dr Jose Herreros (UoB) and Prof Charlotte Bolton (UoN)
In 2013 Ella Kiss-Debrah died of an asthma attack caused by illegally high levels of air pollution in London. Globally traffic related air pollution kills 2.4 million people. Despite this governments are “passing the buck” on action to reduce environmental levels. We understand remarkably little about which constituents of air pollution are detrimental to health or the mechanisms by which they impact on lung health. In this project we combine four leading edge research programmes at the (UoN) (UoN) and the (UoB) (UoB), supported by the respiratory theme of the NIHR Nottingham Biomedical Research Centre, to better understand which constituents of vehicle related PM damage airway cells and how. This project will use cutting-edge technologies and the expert support of the supervisory team to perform detailed characterisation of PM, use and develop novel in vitro airway cell models and profile the immune, remodelling and epigenetic profiles of airway cells. The student will learn fundamental and novel techniques across a broad repertoire including cell co-culture, advanced imaging, molecular biology/epigenetics, soot characterisation, epigenomics data analysis and R programming. The project includes cross institute learning, including the University of Nottingham Faculty of Engineering and School of Medicine and the University of Birmingham.
Dr Alex Wadley (UoB), Dr Francesca Kinsella University Hospitals Birmingham, Prof Afroditi Stathi (UoB) and Dr Alex Thompson (UoN)
Over 90,000 people receive stem cell transplants every year worldwide for illnesses such as blood cancer. Stem cells are an ‘immature’ type of cell that help to rebuild a person’s immune system after treatment. Before a transplant, the patient or a healthy individual donates stem cells for at least 3 hours, but failure rates are approximately 40%. Our initial results indicate that light cycling periods spaced out over 3 hours increases the number of stem cells in collected blood of healthy individuals.
This PhD will take a multi-disciplinary approach to test this idea in a hospital for the first time by allocating donors with myeloma, or healthy individuals to either ‘control’ (normal donation) or ‘cycling’ groups (plus donation). The ‘cycling’ group will pedal lightly for 4 minutes every 20 minutes whilst donating. This PhD will examine whether cycling improves the speed of donation, and whether it is practical and safe. The number and function of collected cells will be examined using contemporary biological techniques and a national survey deployed to evaluate a donor and healthcare professional perceptions.
The candidate will have a background in biological sciences and possess the necessary skills to coordinate a clinical trial and interact with patients.
Dr Harvinder Virk (UoL), Prof Don Jones (UoL), Beatriz Guillen Guio (UoL) and Colleen Maxwell, Cardiovascular Sciences, (UoL)
Industrial partner Abcam Ltd
Interstitial Lung Diseases (ILDs) are a family of lung conditions associated with inflammation and/or fibrosis (scarring). Many ILDs can result in progressive fibrosis and rapid patient deterioration, associated with a large symptom burden and short life expectancy. The available treatments include drugs to reduce inflammation, or slow down progressive scarring (anti-fibrotics). The process for working out which treatment approach(es) a patient will benefit from is slow, expensive and rely on subjective judgements. Cheaper, faster and more robust tests to identify the most suitable treatment approach, or clinical trial, for each patient, are urgently needed.
The project will address this need by using bioinformatics, in-vitro models, and preliminary clinical approaches (blood test development), to identify key molecules that predict ILD progression and response to different treatments. This PhD project is part of an exciting collaboration with Abcam Ltd. (Cambridge) and the (UoN), with the student spending up to 6 months with our collaborating partners. Abcam Ltd. will fund the costs of the placement, including travel and accommodation, and support research costs.
The vision is to enable better patient outcomes by improving utilisation of existing treatments, and better patient selection for clinical trials, by creating robustly validated commercial diagnostic tests.
Prof Ed Hollox, (UoL), Prof Louise Wain (UoL) and Dr Nick Hannan (UoN)
This important and exciting project explores an underappreciated aspect of genetics that could help us understand and treat Idiopathic Pulmonary Fibrosis (IPF), a devastating lung disease with limited treatment options. IPF is challenging because its progression is unpredictable, and current treatments only slow the disease slightly, often with side effects. By focusing on short tandem repeats (STRs)—small, repetitive DNA sequences that vary greatly between individuals—this project aims to uncover how these genetic variations might influence the development and progression of IPF. Discovering how specific STRs impact gene expression could lead to new therapeutic strategies, offering hope for better treatments in the future.
Throughout the project, the student will develop a range of valuable technical skills. These include bioinformatics techniques for analysing large genomic datasets. The student will also gain hands-on experience with molecular biology techniques like luciferase reporter assays, used to study gene regulation, and droplet PCR, a method for precisely measuring gene expression. Although based at the (UoL), the project will also involve time at the (UoN) generating genome-edited models of lung disease in stem cells. These skills will equip the student with expertise applicable across many fields in biomedical science.
Dr Claire Palles (UoB), Prof Chris Denning (UoN), Prof Katja Gehmlich (UoB) and Prof Ninian Lang University of Glasgow
Chemotherapies, including a class of drugs called fluoropyrimidines (FPs), have had an enormous impact improving the survival of patients diagnosed with cancer. They can, however, have a negative impact by causing harmful side effects such as cardiac adverse events. Cardio-oncology is an emerging field trying to understand why some patients are at risk of adverse cardiac effects following treatment with cancer drugs.
We have identified a genetic variant associated with a large increased risk of FP induced cardiovascular toxicity. Variants such as this could be tested for before cancer treatment starts and alternative drugs given to those at high risk. We also hope to identify pathways that can be targeted to protect against FP toxicity.
You will be hosted by supervisors from the Universities of Birmingham and Nottingham. You will learn to culture, genetically modify, differentiate and characterise human pluripotent stem cell derived cardiac cells. You will measure cell properties such as contractility, mitochondrial dysfunction and metabolite accumulation to uncover the mechanism of FP induced toxicity. You will also perform RNA sequencing experiments to understand the pathways altered in the presence of toxicity and test targeting these pathways with cardio-protection drugs.
Dr Laura Sidney (UoN), Dr Felicity de Cogan (UoN), Dr Anna Peacock (UoB) and Dr Darren Ting (UoB)
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.
Prof Aga Gambus (UoB) and Prof Andrew Wilson (UoB)
Inhibition of initiation of DNA replication is an attractive and promising anticancer strategy. We have identified a new peptide that inhibits interaction between key replication initiation proteins and inhibits initiation of DNA replication. The aim of this project is to characterise the mechanism of action of this peptide and determine its potential as a research tool but also as a potential anticancer compound. This is an interdisciplinary project allowing the student to develop skills across a whole portfolio of dimerent techniques. We will determine the kinetics of inhibitor interaction with target proteins using in vitro biophysical assays. We will characterise the molecular mechanism of action of the inhibitor during DNA replication using biochemical approaches in cell free system of Xenopus laevis egg extract. We will use the compound as a tool to freeze the replication machinery at the initiation stage and determine its structure using cryo electron microscopy (cryo-EM). Finally, we will assay its therapeutic potential through testing its emects on viability and proliferation potential of cancerous and non-cancerous cell lines. Altogether, these 4 angles of investigation will give us a comprehensive understanding of the action and usefulness of our new inhibitor.
Dr Caroline Gorvin (UoB), Steve Briddon (UoN) and Joëlle Goulding (UoN)
This PhD project explores how accessory proteins modify signalling of G protein-coupled receptors (GPCRs) involved in appetite regulation, using state-of-the-art assays and cutting-edge microscopy techniques. GPCRs are membrane proteins with critical roles in food intake and energy expenditure. GPCR mutations cause obesity and blockbuster obesity drugs target GPCRs. Interactions between GPCRs and accessory proteins can facilitate GPCR signalling but the molecular mechanisms involved are poorly understood.
This project will explore how accessory proteins interact with GPCRs to modify signalling and trafficking, and how these are affected by obesity-associated mutations. The student will investigate interactions between accessory proteins and GPCRs using fluorescence cross-correlation spectroscopy and assess signalling and trafficking using a variety of assays (e.g. BRET) and advanced microscopy. They will also learn core skills, including cell culture and molecular biology techniques. The candidate will be based primarily at the (UoB) but will undertake research visits to the (UoN) to learn fluorescence cross-correlation spectroscopy. This project provides an exceptional opportunity to engage in multidisciplinary research with access to state-of-the-art facilities at two leading universities. This research will advance understanding of the mechanisms by which GPCRs regulate food intake and could lead to innovative therapies for metabolic disease.
Prof G André Ng (UoL), Dr Reshma Chauhan (UoL), Dr Davor Pavlovic (UoB) and Dr Chris O’Shea (UoB)
Sudden Cardiac Death is a major unsolved clinical problem claiming 100,000 lives annually in the UK. The majority of these deaths are due to lethal heart rhythm disturbances called arrhythmias, often driven by abnormal autonomic nervous system function in heart disease patients. However, due to an incomplete understanding of the underlying mechanisms, there is no effective treatment or preventative therapy. A better understanding of autonomic function and cardiac electrophysiology is essential for the progression of clinical interventions.
The aim of this project will be to investigate the changes in cardiac electrophysiology as a result of heart failure and autonomic dysfunction. This will be explored using our new custom-built panoramic optical mapping system, which gives a 360° view of the heart and can record novel 3D data providing exciting new insights into heart failure and arrhythmia risk.
This project will enable the development of invaluable skills such as surgical skills, experience with in vitro preparations and advanced optical mapping techniques at the (UoL). This project is part of an exciting collaboration with the (UoB) with the opportunity to use innovative new software and produce novel data that will support the development of new clinical therapeutics.
Prof Hansong Ma (UoB), Assistant Prof Luke Chao Harvard Medical School and Associate Prof Yun Fan (UoB)
Are you interested in uncovering the cellular mechanisms that regulate mitochondrial stress responses and exploring cutting-edge biological research? Join our team in investigating the crucial role of inter-organelle communication, where much is still unknown about the regulation of lipid flux upon mitochondrial damages. In our previous work, we identified that compromising mitochondrial DNA and mitochondrial quality control results in a significant accumulation of lipid droplets in Drosophila oocytes and human cells. We hypothesise that mitochondrial stress alters lipid flow, activating a protective mechanism that buffers cellular levels of reactive oxygen species.
In this project, you will engage state-of-the-art 3D electron microscopy to map organelle ultrastructure, identify contact sites, and quantify changes in organelle abundance across different stress conditions. You will leverage lipidomics and genetic tools to pinpoint specific lipid species and pathways, providing critical insights into how lipid droplets are mobilised in response to mitochondrial stress. There will be opportunities to collaborate with our partners at Harvard University and the Janelia Research Campus to access advanced imaging techniques and other methodologies. This work will uncover the mechanisms by which cells adapt to pathological stress, with the potential to develop therapeutic approaches to mitochondrial and other metabolic disorders.
Dr Rahul Mahida (UoB), Dr Amanda Tatler (UoN), Dr Aaron Scott (UoB) and Dr Dhruv Parekh (UoB)
Progressive Pulmonary Fibrosis (IPF) is a devastating condition which causes worsening breathlessness and disability, with a high mortality rate. Macrophage metabolic reprogramming and dysfunction are implicated in IPF pathogenesis, however the mechanisms remain unclear. The aim of this studentship will be to determine the role of extracellular vesicles in mediating macrophage dysfunction and reprogramming in IPF. The objectives will be to characterise the function and metabolic profile macrophages from IPF patients, determine the biological effect of extracellular vesicles on macrophages in vitro and using ex-vivo human lung slice models of fibrosis, and determine whether these effects can be reversed. This is an exciting and highly topical project, which could identify new therapeutic targets for IPF. A range of translational research skills will be taught, including flow cytometry, fluorescence microscopy, qPCR, Seahorse metabolic profiling, macrophage functional assays, electron microscopy, mass spectrometry proteomics, microRNA profiling, digital spatial transcriptomics, and Western blotting. This project benefits from access to human lung tissue from surgical resections; the student will learn how to isolate primary macrophages from tissue, and use precision-cut lung slices in models of pulmonary fibrosis. The student will work collaboratively with an integrated team of discovery scientists and translational clinical academics.
Dr Richard Horniblow (UoB), Prof Iain Chapple (UoB), Prof Zhibing Zhang (UoB) and Prof Kim Hardie (UoN)
Industrial partner Dr Ricarda Hawkins, Haleon, Senior Microbiologist
This PhD project offers an exciting opportunity to explore innovative translational strategies for combatting oral microbiota dysbiosis as a route to maintaining oral health. The oral microbiota, crucial for maintaining a healthy oral environment, often becomes imbalanced (a state of dysbiosis) in conditions including periodontitis and caries. Oral dysbiosis can have significant consequences for overall health, yet no treatment strategies currently exist which can effectively modulate and resolve oral dysbiosis. This project aims to develop microformulations as a tool for restoring healthy oral biofilms. The project will use multidisciplinary approaches from the fields of biochemistry, microbiology and chemical engineering to develop novel composites that can deliver lab-grown healthy oral biofilms within the oral cavity. The project will employ biophysical models to examine and improve biofilm adhesion in simulated oral environments. In addition, in vitro microbial-dental tissue co-culture models will be used to assess the functional and immunological changes that accompany biofilm restoration, shedding light on how inflammatory markers linked to disease are impacted. This research could pave the way for oral microbial transplantation, offering promising solutions for the treatment and prevention of dysbiosis-driven oral and systemic conditions.
Dr Nick Holmes (UoB), Dr Katherine Dyke (UoN) and Dr Max Little (UoB)
How does the brain control the body’s muscles? Can we decode the electrical signals that travel down the spine to the motorneurons of the hand? How do these signals change with age and in people with Tourette syndrome? These fundamental research questions can best be answered with research that cuts across medicine, neuroscience, psychology and computer science. Working across three Schools (Sports Science, Psychology, Computer Sciences), and two Universities (Birmingham, Nottingham) this project offers a fantastic opportunity to learn brain stimulation, electrophysiology, signal processing and machine learning, and to apply these skills to understanding how the human brain produces hand movements in health and disease.
The student will collate existing data from brain stimulation studies of hand movement; analyse those data using advanced signal processing and machine learning algorithms; develop a computational model of how the brain produces individual electrical signals in hand and arm muscles; and apply that model to data collected from a wide range of neurotypical participants and those with Tourette syndrome.
Good mathematical and computer skills are required, but your first and/or MSc degree could be in engineering, neuroscience or related fields – don’t hesitate to get in touch if this sounds like the project for you.
Dr Paul Muhle-Karbe (UoB), Prof Harriet Allen (UoN) and Dr Cathy Manning (UoB)
Atypical allocation of attention has long been reported in autism and has been proposed to underlie varied aspects of the condition. However, existing theories conceive autistic attention in opposing ways, either as narrow focus or as high distractibility. In this project, you will learn about and use cutting-edge tools from computational neuroscience to uncover sources of variability in autistic attention and relate them to everyday functioning, both in terms of strengths and challenges. It will combine expertise in computational modelling, vision neuroscience, and clinical psychology to develop a precise and integrative theory of attention allocation in autism. You will receive in-depth training in cutting-edge quantitative skills such as neural network modelling or EEG frequency tagging. This computational training will be complemented by placements and continuous interaction with our project partners that include clinicians, charities, and autistic people, to understand the real-world implications of atypical attention allocation in autism. You will therefore develop a set of cutting-edge skills and clinical experience in a team of highly supportive scientists at the (UoB) and the (UoN) to develop a clear vision of how to conduct research with impact in the real world.
Prof Nicholas Selby (UoN), Prof Bethan Phillips (UoN), Dr Matthew Graham-Brown (UoL) and Dr Daniela Viramontes Hörner (UoN)
Acute kidney injury (AKI) is a common consequence of acute illness impacting >13-million individuals worldwide each year. Despite this high prevalence and growing recognition of a prolonged symptom burden after recovery from AKI, little attention has been given to potential strategies to improve physical function in AKI patients. Reduced physical function is a substantial burden in those recovering from AKI, postulated to be due, at least in part, to losses of skeletal muscle mass and function during hospitalisation for AKI. Emerging evidence suggests that daily neuromuscular electrical stimulation (NMES) of the quadriceps can reduce losses of muscle mass and function in older cancer patients’ recovering from surgery. However, how this strategy may benefit AKI patients is not yet known. This PhD will use physiological assessments, molecular biology methods and novel imaging techniques to determine: i) the impact of in-hospital NMES on muscle mass and function in AKI patients during their hospital stay and ii) 3-months after hospital discharge; and iii) the potential of an emerging blood-based biomarker to assess muscle mass in AKI patients. Overall, this project will provide the successful candidate with varied skills and experience across the translational research pathway (i.e., bench-to-bedside).
Dr Jose R Hombrebueno (UoB), Prof Parth Narendran (UoB), Prof Fabian Spill (UoB) and Prof Melanie Davies (UoL)
This exciting interdisciplinary and cross-institutional project ((UoB), (UoL) and Mary Lyon Centre at Harwell) aims to test a novel class of therapeutics for the multisystem management of diabetes. Our approach focuses on repairing mitochondria, a major interest of our research group (Nature Communications 2024) which has the potential to revolutionize diabetes treatment, especially given the current lack of preventive therapies.
The selected candidate will pioneer an interdisciplinary PhD project to validate the therapeutic potential of our drug candidates at a preclinical level. You will utilize a wide range of innovative tools (in vivo models, mitophagy reporters, bioenergetic and metabolic assays, molecular techniques, etc) to determine how mitochondrial-based therapies can alleviate related pathology in distal tissues and the immune system. You will also receive additional training in computational modelling of mitochondrial networks, as a potential predictor of multisystem pathology in diabetes including in the clinical setting. This PhD programme offers an exceptional opportunity to join an experienced supervisory team with expertise in translational medicine, diabetes, mitochondrial biology, clinical research, and applied mathematics. This training will equip you with transferable skills to analyse and interpret complex data, enabling the advancement of innovative multi-purpose strategies to improve diabetes care.
Dr Nicholas Hannan (UoN), Prof Gordon Moran (UoN), Gordon, Dr Eva Rodríguez-Suárez AstraZeneca and Dr Gerben Bouma AstraZeneca
Industry partner AstraZeneca
This project aims to develop a single-cell sequencing atlas from intestinal epithelium and blood samples of healthy individuals and IBD patients. You will utilize bioinformatics to analyse differences in gene expression, cell signalling and cell interactions, which will be validated using patient-derived intestinal organoids. This research is crucial for enhancing diagnosis and treatment strategies, enabling personalized therapies that minimize side effects. By contributing to a deeper understanding of IBD mechanisms, your work could significantly improve patient outcomes and reduce the economic burden on healthcare systems.
Additionally, the successful applicant will have the unique opportunity for an industrial placement with AstraZeneca, allowing for collaboration with leading experts and gaining valuable experience in a pharmaceutical setting. This project and industrial placement will enhance your research skills, allow you to develop cutting edge techniques such as single-cell sequencing, bioinformatics, stem cell and organoid biology and cell phenotypin techniques which together will generate insights into the translation of scientific findings into clinical applications.
Dr Boyan Bonev (UoN), Dr Emma Hesketh (UoL) and Dr Andrew Quigley Diamond Light Source and the Research Complex at Harwell
Bacterial resistance to antibiotics is a leading challenge to global healthcare for the coming decade. Particularly difficult to manage are Gram-negative infections, which require the development of new drugs, alongside better education, hygiene and lifestyle. Gram-negative pathogens have an outer membrane, OM, vital to their survival. OM biogenesis requires an essential protein assembly complex, BAM; stalling the BAM is lethal to bacteria. A minimal set of BAM proteins, BamAD, is functional in the pathogen C. jejuni, which offers a unique opportunity to dissect the essential cogs of BAM and to understand its molecular function. By contrast, the BAM complex in E. coli consists of BamABCDE proteins.
In this project, you will learn leading edge integrative structural and computational biology and will apply your knowledge to novel drug design. You will use cryo-electron microscopy and crystallography to characterise the BamAD structure, alongside computational mechanics and NMR to describe its dynamics and interactions, and will employ computational drug design tools to exploit the structural and dynamics information to develop new platform antimicrobial compounds. You will also learn how to test and validate antimicrobial activity. In this project, we will develop a highly selective strategy for management of bacterial virulence, proliferation and invasion of Gram-negative bacteria.
Prof Thomas Schalch (UoL), Prof Clare Davies (UoB), Prof Dean Fennel (UoL) and Dr Yolanda Markaki (UoL)
This PhD project focuses on developing a novel protein-based therapeutic approach to tackle mesothelioma, a highly lethal cancer with limited treatment options. Mesotheliomas often exhibit mutations in the epigenetic regulator and tumour suppressor gene BAP1, making the restoration of its function a key therapeutic strategy. Using a bacterial injection system in combination with various BAP1-deficient cell lines, we aim to deliver functional BAP1 protein directly into tumour cells and restore the epigenetic landscape. We will compare this cutting-edge approach with the traditional lentiviral restoration of BAP1 function. We will investigate how this changes the oncogenic gene expression program and how it can trigger cell death through apoptosis or necroptosis. This groundbreaking approach may open the door to innovative treatments for not only mesothelioma but other cancers with tumour suppressor mutations.
This project will be jointly led by PIs at the Universities of Birmingham and Leicester with experiments performed in both locations. As a PhD student, you will be guided by biochemistry, cell biology and mesothelioma research experts. You will gain expertise in advanced techniques like protein engineering, gene expression analysis, microscopy, and flow cytometry, working closely with leaders in epigenetics, cell and cancer biology, molecular biology, and bioinformatics.
Dr Peter Aldiss (UoN), Associate Prof Caroline Gorvin (UoB) and Assistant Prof Sally Eldeghaidy (UoN)
Excess intake of dietary sugars are a major contributor to obesity, and type 2 diabetes. 82% of consumers state that taste is the major determinant of what they buy and eat – as such, deciphering the mechanisms of sweet taste, and understanding how we can target the ‘sweet tooth’ is key in curbing population-wide sugar intake.
This project aims to understand how inhibiting the pathways responsible for digesting sugar impacts how we taste and perceive sweet foods, and whether we can target this pathway to curb sugar intake at the population level. The student will lead a multidisciplinary project including human pharmacology and nutritional intervention studies in humans where they will acquire skills in sensory sciences, and functional neuroimaging to determine whether inhibition of SI impacts how we sense and taste sweet foods and whether it impacts reward signalling in the brain.
Alongside this, the student will gain expertise in G protein-coupled receptor (GPCRs) biology, signalling assays and advanced imaging as they seek to understand how these genetic variants impact taste-receptor signalling. Finally, the student will gain experience with high-throughput screening of putative therapeutic compounds testing their efficacy at inhibiting key enzymes and taste signalling pathways involved in sugar metabolism and taste.
Prof Suzanne Higgs (UoB), Dr Benjamin I. Perry (UoB), Dr Colin T. Dourish (UoB) and Dr Elizabeth Simpson (UoN)
One of the most pressing problems in psychiatry is the 20-year shortened life-expectancy faced by people with severe mental illnesses like schizophrenia. The most important explanation for this shortened life-expectancy is not the mental disorder itself, but the strong overlap with preventable physical conditions such as diabetes and cardiovascular disease. Yet, intriguingly, research is pointing toward a biological link between body and mind, with the same disease processes leading to both mental and physical ill health.
During this project, the student will be supervised by internationally-leading experts to develop cutting edge skills in data science and epidemiology, then apply those skills in a large database of around 15,000 young adults, to further our understanding of the underpinnings behind co-occurring mental and physical illness.
Further, the student will be supported to develop skills in assessing appetite, impulsivity and metabolic function, and will be supported to apply them by collecting their own data – both from the general population and, supported by an NHS Consultant Psychiatrist, from people with lived experience of mental illness.
Together, this project will improve our understanding of why and how people with mental disorders develop physical health conditions, which is the first step towards preventing them.
Dr Renate Reniers (UoB), Dr Paul Smith (UoB), Dr Rima Dhillon-Smith (UoB), Prof Stephane de Brito (UoB) and Dr Rosalind Baker-Frampton, Clinical Director, Gordon Moody
Industrial partner Gordon Moody
Gambling is a common activity in the UK, with 47.2% of men and 41.7% of women having gambled in the past four weeks. Despite growing evidence that female gambling is on the rise, treatment programmes offered to female gamblers are virtually the same as those offered to male gamblers, leaving female-specific factors largely unstudied. This PhD project offers the exciting opportunity to fill this research gap and investigates variations in gambling behaviour, reward sensitivity, stress, and mental health across the menstrual cycle to identify female-specific factors affecting harmful gambling behaviour and treatment success.
The successful candidate will spend six weeks every four months at Gordon Moody – the UK’s leading charity for gambling addiction treatment. This hands-on experience will include data collection, work on data analytics, and work alongside therapists, recovery workers, and clinicians to gain a thorough grounding in gambling addiction and treatment.
This project will lead to the development of more effective interventions for females experiencing, or at risk for, harmful gambling. The findings will impact Gordon Moody and NHS practices more widely, and influence government policy and funding allocations. This is a unique opportunity to make a tangible difference to addiction treatment.
Dr Katrin Schilcher (UoL) and Prof Joan Geoghegan (UoB)
Are you passionate about advancing our understanding of bacterial pathogens? This project investigates the roles of bacterial lipoproteins in Staphylococcus aureus, a human pathogen linked to various infections and rising antibiotic resistance. By elucidating the interaction partners of these lipoproteins, this research will reveal mechanisms of bacterial adaptation and contribute to the development of innovative therapeutic strategies.
As part of a dynamic collaboration between the (UoL) and (UoB), you will have the opportunity to gain expertise in bacterial genetics, protein co-immunoprecipitation and transcriptomics to analyse gene expression and identify protein interactions. The insights gained will be tested in in vitro and ex vivo virulence models. These experimental approaches will be complemented by bioinformatic analysis, crucial for interpreting transcriptomic data and mapping protein interaction networks, providing deeper insights into the pathways involved in lipoprotein function.
You will have the opportunity to conduct research at both the (UoL) and the (UoB). Join us in tackling the challenge of antibiotic resistance while advancing our understanding of bacterial biology. This project offers a unique opportunity to contribute to impactful research with significant implications for public health.
Dr Katherine Fawcett (UoL), Prof Ian Sayers (UoN) and Prof Chris Brightling (UoL)
Up to 10% of individuals with asthma struggle to control their symptoms despite high intensity treatment, leading to increased risk of hospitalisation and death. We recently performed a genome-wide association study of difficult-to-treat asthma in order to identify genetic risk factors for this condition. However, the causal variants, genes and mechanisms underlying these associated genomic regions is not fully understood. In this project, you will use both computational and experimental approaches to identify the key drivers of difficult-to-treat asthma in these genomic regions. The first 18-24 months of the PhD will be spent in the Genetic Epidemiology Group at the (UoL), an internationally renowned group with a large, vibrant student community. Here, you will learn state-of-the-art statistical genetics and bioinformatics techniques, including analysis of long-read sequencing and multi-omic datasets. You will then have the opportunity to investigate prioritised asthma-associated regions at the prestigious Biodiscovery Institute at the (UoN) using cutting-edge wet-lab techniques such as genome editing in in vitro model systems. This project will provide valuable insights into the biology of difficult-to-treat asthma and potentially inform the development of new therapies for these patients.
Associate Prof Catherine Jopling (UoN) and Dr Michael Tellier (UoL)
In this PhD project, the student will investigate how cancer-associated mutation in the splicing factor SF3B1 affects microRNA biogenesis. SF3B1 mutations are strongly implicated in various cancers but their biological consequences are unclear, although it is becoming increasingly apparent that SF3B1 has functions beyond splicing. We have recently found that SF3B1 inhibition has broad impact on the production of microRNAs, regulatory RNA molecules that are important in cancer. This project will follow on from this work to establish how SF3B1 regulates microRNA biogenesis and whether cancer-associated mutations affect this. This will give novel insight into the role of SF3B1 in cancer with potential to lead to future therapeutic approaches.
This PhD project will be run jointly by the Jopling lab at the (UoN) and the Tellier lab at the (UoL). The student will be mainly based in Nottingham, where they will be part of the friendly and collaborative Gene Regulation and RNA Biology group based in newly refurbished labs in the multidisciplinary Biodiscovery Institute. Here, they will carry out molecular and cell biology research to investigate microRNA biogenesis in cells with and without SF3B1 mutation. The student will also work closely with the Tellier lab to carry out bioinformatic analysis of large datasets, and will therefore acquire skills in state-of the-art wet and dry lab approaches.
Dr James Hodgkinson (UoL), Dr Emma Hesketh (UoL) and Prof John Schwabe (UoL)
Industrial partner Sygnature Discovery (Peak Proteins)
This PhD project is an exciting opportunity to explore the innovative drug strategy PROTACs by Cryo-Electron microscopy, a cutting-edge structural biology technique.
This project involves a close partnership and collaboration with a world-leading drug discovery CRO where the student will learn protein expression/purification amongst industry experts, producing the therapeutic target proteins SOS1 and LSD1.
At Leicester you will learn the chemistry of making PROTACS – novel bi-functional drugs that promise to ‘drug the undruggable’ by marking target proteins for degradation rather than inhibition. To determine the structure-activity relationship of these PROTACS, you will use state of the art cryo-electron microscopy at the regional facility based at Leicester.
SOS1 and LSD1 are both important cancer therapeutic targets with substantial prospect for future drug development:
SOS1 is cytoplasmic guanine nucleotide exchange factor that plays a critical and essential role in the KRAS signalling pathway. Inhibitors of SOS1 have shown considerable potential for targeting RAS-driven tumours.
LSD1 is a histone demethylase enzyme that plays a critical role in the endothelial to mesenchymal transition that is a key step in allowing tumours to metastasize. Inhibition of LSD1 has been shown to be a promising treatment for melanoma in mouse models.
Prof Jessica Blair (UoB), Prof Lindsay Hall (UoB) and Prof Kim Hardie (UoN)
Acinetobacter lwoffii (AL) is a commensal of human skin but is also an emerging opportunistic pathogen that is now the leading cause of Acinetobacter-associated bacteraemia in the UK, ahead of the well-studied antimicrobial resistant (AMR) pathogen Acinetobacter baumannii (AB). Importantly, despite causing similar infections to AB and inhabiting the same niche, AL remains susceptible to antibiotics while AB is frequently highly multidrug resistant (MDR). We have previously shown that development of AMR in AL is constrained. However, the reasons why AL remains antibiotic susceptible, even under selection pressure, remain unclear. The aim of the project is to explain why AMR is constrained in the emerging pathogen AL and how this is influenced by the environment and the skin microbiome. This interdisciplinary project will combine expertise from three leading PIs across the Universities of Birmingham and Nottingham and will provide training in molecular microbiology, AMR, evolution, whole genome sequencing and use of ex-vivo skin models with advanced microscopy techniques. This project will provide critical insights into an important emerging pathogen. Additionally, by understanding why resistance is constrained in AL, we can identify potential strategies for combating AMR in other pathogens, offering novel approaches to tackling this global health threat.