Infection, Immunity and Repair

Projects for an October 2018 start are now available on our Available Projects page. To give you an idea of the types of project that might be on offer, please find below a brief outline of the projects that were advertised for an October 2017 start under the Infection, Immunity and Repair theme below.  Projects for an October 2018 start under this theme can be found here.

 

Imaging and modelling for prevention of heart failure following myocardial infarction
To better understand the progression to heart failure following a heart attack, a combined approach of computational modelling, PET/CT imaging and rodent experimental models will be harnessed, forming a key step in the creation of a novel pipeline for accelerating the development of the next generation of therapies for cardiovascular diseases.
Supervisor: Dr Andrew Cookson.
Lead Institution: Bath University.


Development of a multiplex sensing platform for accurate and rapid diagnosis of sepsis

Sepsis kills one person every few seconds. Clinical symptoms and current laboratory diagnostics do not allow definitive early diagnosis. This collaborative project aims to address this shortcoming through the development of a novel sensing platform, capable of detecting both pathogen associated and host immune markers of sepsis at point-of-care.
Supervisor: Dr Pedro Estrela.
Lead Institution: Bath.


Structural and functional analysis of a supra-molecular assembly crucial for Staphylococcus aureus immune evasion

Immune evasion protein Sbi enables human pathogen Staphylococcus aureus to escape elimination by activating the innate immune system. This project aims to gain understanding in this process by studying the supra-molecular complex formed between Sbi and complement proteins and how this can be used to design new vaccines and immunotherapies.
Supervisor: Dr Jean van den Elsen.
Lead Institution: Bath.


Understanding the functions and therapeutic potential of the Shigella surface protein IcsA

This project aims to study, at the cellular and molecular level, the multiple functions of the Shigella surface protein IcsA during shigellosis, in order to develop its use as a vaccine antigen.
Supervisor: Dr Ariel Blocker.
Lead Institution: Bristol.


New antimicrobials from deep-sea sponges

Marine natural products are an untapped reserve of potent antibacterial agents. The student will isolate and characterise new antibiotics from the microbial biota of deep-ocean sponges. This interdisciplinary project will provide training in microbial cultivation, natural product chemistry, next-generation sequencing and susceptibility screening.
Supervisor: Dr Paul Curnow.
Lead Institution: Bristol.


Role of Class I PI3 kinase in platelet-leukocyte interactions, innate immunity and deep vein thrombosis 

Both platelets and leucocytes are key players in causing deep vein thrombosis (DVT), a leading cause of cardiovascular death. This project will study the role of PI3kinase in cross-talk between platelets and innate immunity and how this contributes to DVT.
Supervisor: Dr Ingeborg Hers.
Lead Institution: Bristol.


Modelling cancer biopsy and radiotherapy in zebrafish and man

This project will utilise live imaging studies in translucent zebrafish to investigate how cancer biopsy/surgery and radiotherapy impact on the local innate and adaptive immune response and how this alters cancer progression for various cancer types.  The work will lead onto clinical studies using patient samples.
Supervisor: Professor Paul Martin.
Lead Institution: Bristol.


Factors involved in expression and secretion of the Streptococcus pneumoniae cytotoxin pneumolysin

Streptococcus pneumoniae causes significant disease worldwide. A critical virulence factor is toxin pneumolysin (Ply). This project utilises a combination of genetic and proteomic approaches to determine the molecular basis of Ply expression and secretion. Such information will aid development of novel strategies to combat pneumococcal disease.
Supervisor: Dr Angela Nobbs.
Lead Institution: Bristol.


Molecular Basis of Mobile Colistin Resistance in Gram-negative Bacteria

Colistin is a last resort antibiotic for infections by Gram-negative bacteria. Recently we described MCR-1, a transmissible colistin resistance mechanism, in E coli from China. Subsequently MCR-1 has been identified worldwide. This project aims to determine a crystal structure for MCR-1 and establish the basis for its activity.
Supervisor: Dr James Spencer.
Lead Institution: Bristol.


General and efficient computational assays for antibiotic breakdown by β-lactamases

β-lactamase mediated resistance to existing antibiotics is a major threat to human health. We can now use atomistic simulation to predict this type of resistance. The project aims to develop efficient in silico assays for all serine β-lactamases, to allow their use in identifying new resistance-conferring enzymes and aid future antibiotic design.
Supervisor: Dr Marc van der Kamp
Lead Institution: Bristol.


Addressing cellular interactions in tumours in vivo to control tumour immunity

The immune system can eliminate tumour cells, yet such anti-tumour immunity is largely suppressed in the tumour microenvironment. Here we will use in vivo imaging in combination with genetic manipulation to understand and overcome limitations in how immune cells access a tumour, regulate tumour vascularisation and kill tumour target cells.
Supervisor: Professor Christoph Wuelfing.
Lead Institution:
Bristol.

 

Investigating the impact of metallic nanoparticles on biological systems and lysosomal function
Metal nanoparticles are increasingly used in biomedicine but their toxic impact on biological systems remain largely unknown. This multidisciplinary project, combining cell biology and chemistry, aims to explore the effects of these nanoparticles on lysosomal function in the immune system and explore how they enter the brain and induce damage.
Supervisor: Dr Emyr Lloyd-Evans.
Lead Institution: Cardiff.

 

New synthetic biology approaches to antibiotic resistance detection and treatment
You will undertake a PhD in synthetic biology that uses engineered BLIP proteins as novel detection and treatment methods to tackle the growing threat of microbial resistance to antibiotics. You will target beta-lactamase enzymes, which are responsible for resistance to the most important and commonly used antibiotic class, the penicillins.
Supervisor: Dr Dafydd Jones.
Lead Institution: Cardiff.

 

Characterising Intra-host Spread of Clinical Human Cytomegalovirus 
Cytomegalovirus (CMV) is the leading viral cause of congenital malformation, and a major issue in the immunocompromised. CMV spreads through the host by direct cell-to-cell spread; this project will use unique technologies and cutting-edge ‘omics’ techniques to dissect both the mechanisms and pathological consequences of this method of spread.
Supervisor: Dr Richard Stanton.
Lead Institution: Cardiff.

 

Defining the true extent of macrophage diversity in diseases such as infection, heart disease and cancer
Macrophages play important roles in diseases such as infection, cancer and heart disease but their true diversity and the specific roles of subsets remain unknown. We will use state-of-the-art technologies to understand what individual cells do in specific disease contexts building on our discoveries in tissues (PMID: 24762537).
Supervisor: Professor Philip Taylor.
Lead Institution: Cardiff.

 

Development of Cytomegalovirus-Based Vectors in Cancer Vaccination
Cytomegalovirus (CMV) vaccine vectors stimulate potent T-cell responses. This project will develop cancer vaccines based on unique replication-deficient CMV vectors that are safe for use in humans. In combination with cutting-edge immune modulatory approaches, we will examine anti-cancer immune responses and protection induced by these vectors.
Supervisor: Dr Ian Humphreys.
Lead Institution: Cardiff.

 

Innate immune recognition of needle-like structures from bacterial pathogens
This project aims to investigate, at the cellular and molecular level, the interactions of the type III secretion system (T3SS) “needle” proteins and “tip” complexes from Y. pestis and Shigella with the innate immune system in order to determine how these proteins subvert the host response to promote infection.
Supervisor: Professor Kathy Triantafilou.
Lead Institution: Cardiff.

 

Integrative multi-omic study of progression to Nonalcoholic Steatohepatitis
Nonalcoholic steatohepatitis (NASH) affects up to 5% of the UK population and is now considered to be one of the main causes of cirrhosis. What determines the progression to NASH is not clear. The student will develop a high-dimensional model to profile the pathogenic processes of NASH by using cutting-edge systems biology approaches.
Supervisor: Dr You Zhou.
Lead Institution: Cardiff.

 

MicroRNA regulation of kidney macrophage function in diabetic kidney disease
Macrophages are key to Diabetic Kidney Disease (the commonest cause of kidney failure) and also to kidney injury repair. This studentship will uncover the roles of microRNAs in specifying these macrophage phenotypes in the kidney, using state of the art techniques to study cells isolated from a mouse model and from human disease.
Supervisor: Professor Donald Fraser.
Lead Institution: Cardiff.

 

Role of tissue-resident monocytes (Mtr) in wound healing
Wound repair is essential for tissue health and longevity. We propose that tissue-resident monocytes (MTR), a novel immune cell subset, control this process. The GW4 BioMed student will examine this hypothesis in vitro and in vivo under the supervision of experts in immune cell migration and tissue macrophages (Cardiff) and wound biology (Bristol).
Supervisor: Professor Bernhard Moser.
Lead Institution: Cardiff.

 

Stem Cell Exosomes; a system for initiating tissue repair and regeneration in diverse disease settings
Cardiovascular progenitor cells (PCs) created hope for vascular regeneration. However, PCs’ drive effects through secretion of molecules and vesicles (exosomes), and their actions depend on the microenvironment, which is made unfavorable by the disease. The project will study exosomes as therapeutic alternative to PCs for vascular regeneration.
Supervisor: Dr Jason Webber.
Lead Institution: Cardiff.

 

The role of chromatin modifications in immune diversification and tumorigenesis
The DNA damage response, highlighted in this year’s Nobel Prize, plays a critical role in preserving genomic integrity against cancer. Paradoxically, it also promotes mutagenesis to stimulate antibody diversity against immunodeficiency. This project aims to study the role of a new chromatin modifier on antibody diversification and cancer.
Supervisor: Dr Richard Chahwan.
Lead Institution: Exeter.

 

Eradicating antimicrobial resistance genes from human pathogen communities using CRISPR-Cas9
Antimicrobial resistance (AMR) is one of the greatest threats to human health of our time and discovering ways to prevent the spread of AMR would be truly ground breaking. This project develops the CRISPR-Cas9 genome editing system to target and destroy AMR genes in complex microbial communities present in the lungs of cystic fibrosis patients.
Supervisor: Dr William Gaze.
Lead Institution: Exeter.

 

Combatting antibiotic resistance by targeting the sensory networks that control pathogenicity
Antibiotic resistance is a major problem in the treatment of bacterial infections. Novel ways of tackling infection are urgently needed. Bacteria rely upon sensory networks to sense threats and to respond accordingly. This project aims to assess the potential of targeting these sensory networks that bacteria depend upon for their survival.
Supervisor: Dr Steven Porter.
Lead Institution: Exeter.

 

Epigenetic profiling of circulating DNA as a marker of dysregulated tissue repair in lung disease
Cutting-edge sequencing and epigenetic profiling will be used to seek novel circulating DNA and RNA signatures (biomarkers) in blood samples from patients with terminal lung disease. This will aid diagnosis and prediction of drug responsiveness, while offering insights into the disease pathogenesis (which will be explored using lab-based assays).
Supervisor: Dr Chris Scotton.
Institution: Exeter.

 

Serum nitrate as a biomarker of infection in gastroenteritis patients
Patients with infective gastroenteritis show extreme increases in serum nitrate levels due to high nitric oxide synthesis. Do blood serum nitrate levels reveal the cause of acute diarrhoea in patients admitted as emergency cases to hospital, and can a novel electrochemical sensor facilitate rapid bedside measurements of nitrate?
Supervisor: Professor Paul Winyard.
Institution: Exeter.

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