INFECTION, IMMUNITY, ANTIMICROBIAL RESISTANCE AND REPAIR

The details of the available projects for the Infection, Immunity, Antimicrobial Resistance & Repair theme are outlined on this page. You can find other projects on the Neuroscience & Mental Health and Population Health Sciences pages. A full list of our available projects can be downloaded below.

GW4 BioMed2 MRC DTP – Full list of available projects 2023-24

For full project descriptions, including contact details for the lead supervisor, click the download link on the project title.

Applications to the GW4 BioMed2 MRC DTP will be accepted via this online form until 5pm on Wednesday, 2 November 2022. For guidance on the application criteria and decision timeline, please see the information here.


AVAILABLE IIAR PROJECTS

How are antifungal usage and environment change on our farms driving cross-resistance in clinical pathogens?

Fungal pathogens cause deadly human infections, destroy our crops, and contaminate our food with toxins. Fungal pathogens of people are also present on our farms. Worryingly, we rely on a few antifungals to cure human infection and to secure our safe food supply. Here, we aim to understand how our changing environments and use of antifungals on farms may drive human pathogens to evolve cross-resistance to clinical treatments that result in poor patient outcomes.

Lead Supervisor: Dr Neil Brown
Institution: Bath


Integrating biology and population health science to investigate obesity and deficient wound healing

Obesity is a systemic disease that disrupts many cell and tissue functions, with impaired healing a key complication. This project will investigate the impact of obesity on deficient wound healing by integrating approaches from the biological and population health sciences. Key tools include epidemiological multi-omics data, zebrafish transgenesis and imaging, and human tissue culture assays, to reveal potential therapeutic targets for improving patient outcomes.

Lead Supervisor: Dr David Gurevich
Institution: Bath


Evolution of antimicrobial resistance in bacterial microbiomes

Biocides are broad spectrum antimicrobial agents used extensively in healthcare as antiseptics and disinfectants. Working with the United Kingdom Health Security Agency, you will employ molecular, genomic, bioinformatic, and directed evolution techniques, in conjunction with models of polymicrobial infection, to answer fundamental questions about the role of biocides in evolution of antimicrobial resistance. 

Lead Supervisor: Dr Brian Jones
Institution: Bath


Escaping host immunity: Characterising immune evasion mechanisms employed by the bacterial pathogen Staphylococcus aureus

The complement system plays a major role in defence against infection. How major human pathogens such as Staphylococcus aureus resist this element of host immunity is currently unclear. By employing gold-standard phenotypic, transcriptomic and functional genomic techniques, this project will reveal important virulence factors and virulence gene regulatory networks that promote resistance to complement, offering new targets for future therapeutic intervention.

Lead Supervisor: Dr Maisem Laabei
Institution: Bath


Targeting adipose – derived adipsin for the treatment of arthritis

Adipose tissue is much more than an energy store. Recent evidence from rodent models indicates that a major product of adipose tissue (adipsin) plays a direct role in the pathogenesis of immune mediated inflammatory arthritis. This interdisciplinary project will determine the role of adipsin in humans, including whether targeting adipsin has the potential to prevent and/or treat inflammatory arthritis and osteoarthritis.

Supervisor: Prof Dylan Thompson
Institution: Bath


A novel, bacterial quorum sensor-infused nanocarrier drug delivery system to tackle antimicrobial resistant fungi

The lack of effective drugs to manage deadly fungal infections in immunocompromised patients emphasised the dire need for novel therapeutics in combating healthcare associated infections (HAI). Using cutting-edge microbiological and drug delivery approaches, this project will probe the potential for bacterial chemical signals to eliminate invasive fungal pathogen, Candida. Findings will establish a prototype of a novel therapeutic alternative to fight fungal HAI.

Lead Supervisor: Dr Nihal Bandara
Institution: Bristol


Investigating senescence in osteoarthritis 

The accumulation of senescent, ‘zombie’ cells cause tissue dysfunction and human disease including osteoarthritis (OA). This PhD project will investigate how growth, metabolism, and survival pathways are different between senescent and healthy cells. We will then explore how senescence contributes to OA pathology and whether we can prevent or reverse it.

Lead Supervisor: Dr Bernadette Carroll
Institution: Bristol


Accelerated prediction of virulence and antibiotic susceptibility for bacteria causing bloodstream infections using MALDI clinical diagnostics

In life-threatening infections, timely and appropriate antibiotics improve outcomes but testing for antibiotic sensitivities is slow. Our novel machine learning helps detect bacterial types associated with enhanced virulence and resistance from routine MALDI mass spectrometry data. You will develop and validate this approach for clinically-important Klebsiella pneumoniae and Escherichia coli additionally performing gene knockout experiments and bioinformatics.

Lead Supervisor: Prof Andrew Dowsey
Institution: Bristol


Identifying immune mechanisms and testing new therapeutic targets for inflammatory arthritis and associated comorbidities

Cytokine-blocking drugs have revolutionised the treatment of inflammatory arthritis. However, ~40% of patients show poor responses to these drugs, continue to display severe disease and also suffer comorbidities (e.g. cardiovascular disease, uveitis). The student will use in vivo arthritis models, imaging, and bioinformatics to test the therapeutic potential of targeting coexisting immune mechanisms active in arthritic joints and tissues affected by comorbidity.

Lead Supervisor: Dr Gareth Jones
Institution: Bristol


Immune and therapeutic implications of intratumour bacteria

Intratumour microbiota (i.e. bacteria living inside tumour cells) is an emerging hallmark that has been clinically validated in many tumour types. You will study the role of intratumour microbiota in promoting chemoresistance and characterise the associated tumour immune microenvironment. Once validated, this project will be the first demonstration of how intratumour microbes alter tumour behaviours, paving the way to more mechanism-directed clinical interventions.

Lead Supervisor: Dr Siang-Boon Koh
Institution: Bristol


Sticky but not sweet: deciphering how Streptococcus bacteria drive clot formation and heart disease

Streptococcus bacteria cause heart disease infective endocarditis (IE), for which novel therapies are urgently needed. Bacterial protein PadA is critical to IE pathogenesis but how it functions is unknown. This project combines molecular/clinical microbiology, host immunity and structural biology to identify the mechanisms by which PadA aids bacterial survival in blood and drives the harmful clot formation seen with IE. Such insight is critical to IE therapy design. Dr Angela Nobbs

Lead Supervisor: Dr Angela Nobbs
Institution: Bristol


Understanding how extracellular vesicles influence inflammation during tissue regeneration in zebrafish

Zebrafish have a remarkable ability to regenerate damaged tissues. Tissue repair and regeneration requires communication between multiple different cell types including immune cells, fibroblasts and endothelial cells. Extracellular vesicles (EVs) deliver molecular messages between cells and our data suggests they promote regeneration. This project will determine how EVs might be harnessed to facilitate optimal repair of damaged tissues via influencing inflammation.

Lead Supervisor: Dr Rebecca Richardson
Institution: Bristol


Exploiting glycan interactions for bacterial detection

Bacterial infections acquired in the community (e.g. tuberculosis (TB)) or healthcare settings (e.g. Staphylococcus aureus/MRSA) are a global public health burden exacerbated by growing antimicrobial resistance and slow antimicrobial drug development. Bacteria exploit specific carbohydrates (glycans) during the infection process. This project explores how bacteria interact with synthetic glycans, and how these might be developed as tools for detecting infections.

Lead Supervisor: Prof James Spencer
Institution: Bristol


Does microplastic exposure cause immune dysfunction and impact our health?

Humans are estimated to consume millions of microplastics (MPs) each year, but exactly how MPs impact our health is alarmingly unclear. In this project, we will identify the molecular consequences of MP uptake on cells and tissues, and explore whether prolonged MP exposure even weakens immunity. We will integrate in vivo animal models with in vitro analyses of human cells and state-of-the-art imaging, and engage with chemists to test novel bioplastic alternatives. 

Lead Supervisor: Dr Helen Weavers
Institution: Bristol


Unravelling cell entry and intracellular trafficking of adenoviruses at the nanoscale using coherent optical nanoscopy

Adenoviruses (AdV) are promising candidates as vectors for gene therapies, yet they follow a complex intracellular journey which needs to be fully understood for the design of optimised constructs. The project will exploit a novel single virus tracking technology using photostable gold nanoparticle probes, to directly pinpoint the mechanism of cell entry and intracellular trafficking pathways of different AdV serotypes with unprecedented spatio-temporal resolution

Lead Supervisor: Prof Paola Borri
Institution: Cardiff


Investigating novel chronic kidney disease therapies that regulate expression of long noncoding RNA hyaluronan synthase 2-antisense 1 (HAS2-AS1)

Chronic kidney disease (CKD) affects 15% of the global population but has no cure. This project will investigate a novel therapeutic approach to halting CKD progression, by using a long noncoding (lnc)RNA that is relevant to kidney disease. The student will explore the role of lncRNA HAS2-AS1 in the regulation of kidney fibrosis using cell and in vivo models, and then translate these findings by manipulating HAS2-AS1 expression in models of CKD therapy.

Lead Supervisor: Dr Timothy Bowen
Institution: Cardiff


Novel tools for analysis of high-dimensional cytometry data: implications for patients with severe dengue

Cytometry – the method of identifying and counting cells – is a cornerstone of biomedical research and clinical practice. Cytometry generates massive datasets too unwieldy to manage efficiently, thereby slowing down scientific progress. We aim to empower scientists to analyse and interpret complex data at a quality, speed and reproducibility never seen before, by developing novel mathematical approaches and apply them to immune profiles of dengue patients.

Lead Supervisor: Prof Matthias Eberl
Institution: Cardiff


Combating cancer with data science: Deep learning of histological images for the detection of lymph node metastases

Lymph nodes are a common site for the spread of cancer. The student will learn state-of-the-art techniques in Data Science involving Deep Learning to detect cancer automatically in lymph-node histology images. This will alleviate the workload of trained histologists in the UK, who struggle to keep up with demand. It will lead to earlier detection and lives saved. Training across two GW4 universities will be immersed in strongly multidisciplinary environments.

Lead Supervisor: Dr Damian JJ Farnell
Institution: Cardiff


Tracking the genetic link between neurodevelopmental conditions, inflammation and kidney disease

Population studies have identified genetic traits linked with neurodevelopmental disorders. Patients with these conditions often display an increased risk of kidney disease. The genetic and molecular basis for this joint susceptibility profile is unknown. Combining training in genetic epidemiology with immune pathology and molecular cell biology studies, the successful applicant will investigate the regulatory mechanisms responsible. 

Lead Supervisor: Prof Donald Fraser
Institution: Cardiff


T cell immune modulation during severe bacterial infection

There is no licensed vaccine against Staphylococcus aureus which produces life-threatening bloodstream infections (“bacteraemia”) and has evolved antibiotic-resistant strains. However, mucosal-associated invariant T (MAIT) cells can combat certain antibiotic-resistant bacteria, positioning them as ideal targets for new vaccines. The student will examine how MAIT cell responses against Staphylococcus aureus are affected by the bacterium during bacteraemia.

Lead Supervisor: Dr James McLaren
Institution: Cardiff


Defining the adenoviral “interactome” to develop safer and more efficacious virus-based therapies

The AZ adenovirus-based coronavirus vaccine has prevented ~6M COVID deaths worldwide. Nevertheless, interactions with host proteins have resulted in rare adverse blood clotting events, harming vaccine confidence. This highlights the need to define proteins interacting with adenoviruses prior to clinical role out. This project will develop methodologies to achieve this, defining the viral “interactome” to develop safer platforms for therapeutic applications.

Lead Supervisor: Prof Alan Parker
Institution: Cardiff


Epigenetic regulation of microglial gene expression in Alzheimer’s disease

Neuroinflammation is a prominent event in Alzheimer’s disease (AD) pathogenesis driven by activation of microglia, the brains resident immune cells. To define how microglial gene expression is regulated in AD, this project utilises a state-of-the-art human induced pluripotent stem cell models of AD coupled with epigenomic profiling and bioinformatic analysis. The role of prioritised genes will then be described through functional assays of key microglial processes.

Lead Supervisor: Dr Owen Peters
Institution: Cardiff


De novo synthekines for treatment of autoimmune diseases

Inflammation is essential for responding to infection and tissue damage. Its dysregulation, however, causes autoimmune diseases and chronic inflammation. Modulating cytokine activity has emerged as an important therapy for autoimmune conditions such as rheumatoid arthritis and uveitis. In this project you will computationally design new-to-nature proteins that mimic cytokines and test their therapeutic potential in autoimmunity.

Lead Supervisor: Dr Guto Rhys
Institution: Cardiff


Enhancing immunological control of SARS-CoV-2

Neutralizing antibodies are key to preventing transmission of SARS-CoV-2, however the virus can rapidly mutate to avoid these. Furthermore, once infected, neutralizing antibodies cannot access intracellular virus. At this point, antibodies that recognise the infected cell become critical. However, current vaccines fail to induce these. This proposal will investigate how this activity can be induced, as the basis for next-generation and variant-resistant vaccines.

Lead Supervisor: Prof Richard Stanton
Institution: Cardiff


Generating killer cells for immunotherapy against cancer and pathogens

Natural killer cells (NK) and CD8+ cytotoxic T lymphocytes (CTL) protect us by killing cells infected with intracellular pathogens and cancers. This project aims to work out what drives the growth of types of NK and CTL that are optimised to protect against these diseases, using state-of-the-art technologies (proteomics, advanced flow cytometry), unique libraries of viruses (adenovirus and cytomegalovirus) and clinical samples (leukaemias) as systems of analysis.

Lead Supervisor: Prof Eddie Wang
Institution: Cardiff


Investigating the therapeutic potential of microwaves in chronic wound healing

Chronic wounds are a significant economic and societal burden. Bacterial biofilms are regular colonisers of chronic wounds, with treatment failure common. Microwaves will be investigated as a potential therapy for chronic wounds via a dual approach of biofilm disruption and promoting healing through fibroblast stimulation. A clinical prototype will also be designed based on patient feedback and an interdisciplinary skillset will be developed.

Lead Supervisor: Dr Helen Brown
Institution: Cardiff


Pharmacological targeting of AMP-activated protein kinase for immune cell regulation in Type 1 Diabetes

The ambition of this project is to discover new approaches to dampen the immune-mediated attack on the pancreatic beta cell seen in type-1 diabetes. Using immune cells from healthy and diabetic pre-clinical research models, this project will employ pharmacological approaches to measure production of inflammatory and cytotoxic molecules as well as assessment of how novel drugs affect immunometabolism, an emerging area of research involved in many diseases.

Lead Supervisor: Dr Craig Beall
Institution: Exeter


Optimising phage cocktails for treatment of drug resistant pathogens associated with cystic fibrosis

Phage cocktails promise treatments for antibiotic-resistant infections but are arbitrarily composed. They do not account for phage cross-resistance (resistance to one phage confers resistance to others), especially alongside antibiotics or immune responses. Using new high-throughput phage resistance assays and genomics the student will deliver phage cocktails that avoid cross-resistance and maximise effect in combination with antibiotics and innate host immunity.

Lead Supervisor: Dr Remy Chait
Institution: Exeter


Developing novel microfluidic platforms for antibiotic discovery

AS THIS PROJECT IS AN INDUSTRIAL PARTNERSHIP WITH DSTL IT CAN ONLY BE SELECTED AS A FIRST CHOICE, NOT A SECOND CHOICE PROJECT AND IS ONLY AVAILABLE TO UK CITIZENS

Antimicrobial resistance is one of the most pressing public health challenges and threatens the ability to effectively fight infectious diseases, with around 10 million people predicted to die annually of infections by 2050. This project will tackle antimicrobial resistance by developing a biodiscovery pipeline for the isolation of bacteria and for the discovery of new antibiotic leads from previously uncultured microbes.

Lead Supervisor: Prof Stefano Pagliara
Institution: Exeter


Does resistance to antimicrobial peptides help bacteria avoid immunity and become more harmful?

Antimicrobial peptides are a potentially rich source of new antibacterial drugs.  However, peptides also form part of the defence systems of many animals.  The project will combine protein synthesis with genomics, and experiments in an insect model.  It will investigate whether evolved resistance to a range of peptide structures also confers resistance to innate immunity peptides and how resistance affects the ability of bacteria to infect and harm hosts.

Lead Supervisor: Prof Ben Raymond
Institution: Exeter


Modelling human embryo development: a combined mathematics and lab approach

During this PhD, you will use mathematics, computer programming and lab-based experiments to investigate how the human embryo develops, focusing on the very first few days after fertilisation when the embryo grows from a single egg to several hundred cells. The findings will have important implications for improving IVF treatment. Unlike most PhDs, this is an excellent opportunity to be trained in both the experimental and mathematical aspects of modern research.

Lead Supervisor: Dr David Richards
Institution: Exeter


Quantitative analysis of Wnt signalling in the gastric tumour microenvironment

Gastric cancer is a multifactorial disease-causing over a million deaths yearly. Deregulation of oncogenic cell signalling, such as the Wnt signalling pathway, leads to tumour growth and metastasis. In this project, the student will apply novel microfluidic tools to decipher the function of Wnt signal spreading and activation in the tumour microenvironment to develop effective new therapeutics to combat gastric cancer.

Lead Supervisor: Dr Steffen Scholpp
Institution: Exeter


Mapping pathogen transport and retention near ciliated surfaces

Cilia fulfil numerous physiological functions. From protists to mammals, cilia have highly conserved structure and function. In humans, motile cilia beating in our airways are a critical first line of defence against bacterial, fungal and viral infections. This interdisciplinary PhD will provide the first comprehensive biophysical study of how the rich dynamics and topology of different ciliated surfaces conspire to control the fate of foreign particles/pathogens.

Lead Supervisor: Dr Kirsty Wan
Institution: Exeter


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