Applications are now open for 18 fully funded PhD studentships offered through the BBSRC-funded Wessex One Health (WOH) doctoral programme, starting in October 2026. This interdisciplinary programme focuses on Infection Biosciences, training students to tackle major disease threats to human and animal health, including emerging infections, vector-borne diseases, antimicrobial resistance, food insecurity, and zoonotic pathogens.
The studentships are fully funded for 4 years, covering a UKRI-rate stipend (currently £20,780 per annum), tuition fees (UK level), and research costs. A small number of international fee waivers are available, making the programme accessible to outstanding international applicants. Projects involve cross-institutional supervision and access to world-class facilities at partner institutions, including high-containment laboratories.
The programme welcomes applicants with or expecting a first or upper second-class honours degree (or MSc) in a relevant subject. Laboratory experience is desirable but not essential, as training will be provided. There is no application fee.
Application deadline: Midnight, Friday 23 January 2026
All Available Positions (Please click on specific project to view details)
Project 1: Spatial Relationships in Skin Infections – Insights from Buruli Ulcer
Theme(s): Infection and Cellular Biology
Lead Partner: University of Surrey
Supervisor: Rachel Simmonds, [email protected]
Joint Partner: APHA
Supervisor: Javier Salguero-Bodes, [email protected]
Project Summary Skin is a highly complex organ, which is an essential and effective barrier to infection. Yet some pathogens are able to overcome these protections and infect skin. Spatial relationships can be visualised experimentally using tissue sections and specific stains. In the past, our understanding of the interaction between pathogens and different cells within skin was undertaken on a case-by-case basis. However, recent advances in technology mean that it is now possible to observe the behaviour of many markers at once. These exciting approaches are extremely powerful tools to understand host-pathogen interactions.
Prof Simmonds’ group (University of Surrey) works on Buruli ulcer, a chronic skin infection caused by a bacteria in the same family as TB and Leprosy. The disease is important in West Africa and Australia, and is of great interest because of the lack of typical signs of infection such as pain and inflammation and is hard to treat even in high-resource settings. Our research has shown that the interaction between the bacteria and macrophages may be important in controlling changes in the skin that determine whether an infection results in clinical disease.
In this project, and in collaboration with Prof Javier Salguero-Bodes (UKHSA) you will use cutting edge multi-analyte phenotyping to investigate the interaction between Mycobacterium ulcerans and different cells in the skin experimentally infected animals. To investigate the mechanisms involved, you will use genetically engineered animals, and/or animals treated with drugs that change immune cell function and analyse changes in these spatial relationships.
You will receive excellent training in cellular and molecular biology, as well as experimental models of infection, including work in high containment. You will be part of a worldwide effort to understand this neglected disease, and the research is expected to help us design better treatments to shorten healing times in Buruli ulcer patients.
Please apply by submitting an application form and completing our EDI survey.
Project 2: Honeybee Hives as Sentinels for Infectious Diseases
Theme(s): Detection, Prevention and Intervention
Lead Partner: University of Surrey
Supervisor: Dr Jorge Gutierrez-Merino, [email protected]
Joint Partner: APHA Supervisor: Dr Paul Beales, [email protected]
Project Summary Honeybee hives may hold the key to tracking infectious diseases in our environment. This project investigates how the unique microbial communities within honey and beebread can act as early warning indicators for pathogens affecting plants, animals, and humans across the UK.
As honeybees forage for nectar and pollen, they also collect microbes from plants, soil, water, and waste. Our recent research, published in Environmental Microbiome (2023), showed that each hive possesses a distinctive microbial fingerprint, containing genetic traces of bacteria linked to both plant and zoonotic diseases.
Please apply by submitting an application form and completing our EDI survey.
Project 3: Advancing a Lymph-Node Targeting Bacterial Vaccine Platform for One Health Pathogens
Theme(s): Detection, Prevention and Intervention; Infection and Cellular Biology
Lead Partner: University of Surrey
Supervisor: Dr Matthew Siggins, [email protected]
Joint Partner: APHA
Supervisor: Dr Amin Asfor, [email protected]
Project Summary Antimicrobial resistance is a major One Health and global challenge. As antibiotics lose effectiveness, bacterial infections in humans and animals are becoming harder to treat. Vaccines are a critical tool to reduce antibiotic use and control AMR, but for many priority pathogens they remain unavailable or inadequate. Building on our Nature Communications discovery that hyaluronan promotes bacterial transit to lymph nodes via the lymphatic system, this project advances VAXHA, a versatile live bacterial vaccine vector designed for low-cost manufacture and global use. By directing antigens to lymph nodes—where durable immune responses are generated—VAXHA is designed to produce stronger and longer-lasting antibody and T-cell protection than conventional approaches.
Working within advanced, specialist facilities across the University of Surrey and APHA, the student will progress through three phases: first, molecular engineering of the live bacterial vaccine platform to enhance performance and safety; second, immune profiling to determine how lymph-node targeting shapes the quality and durability of B- and T-cell responses, integrating quantitative ex vivo and in vivo readouts; and third, protection studies in vivo to test whether improved delivery translates into stronger, longer-lasting immunity. Methods will include fluorescence microscopy, flow cytometry, cell culture, and AI-driven analysis.
Full interdisciplinary training will be provided across microbiology, molecular biology, immunology, and data science. Students will have opportunities to present their work, collaborate across partners, and undertake diverse professional skills training. Ultimately, this project will uncover how lymph-node targeting orchestrates improved protective B- and T-cell immunity, and it will advance the VAXHA vaccine platform towards practical use across a range of One Health pathogens.
Please apply by submitting an application form and completing our EDI survey.
Project 4: Environmental Adaptation of Mycobacterium bovis and Its Impact on Infectivity
Theme(s): Detection, Prevention and Intervention, Understanding Disease Spread, Infection and Cellular Biology
Lead Partner: University of Surrey
Supervisor: Graham Stewart, [email protected]
Joint Partner: APHA
Supervisor: Daryan Kaveh, [email protected]
Project Summary Mycobacterium bovis is the causative agent of bovine tuberculosis (bTB) and the predominant cause of zoonotic tuberculosis worldwide. In the UK and Ireland, control of bTB is complicated by a reservoir of infection in badgers. Transmission between badgers and cattle (and vice versa) is not well understood but may involve an environmental step between hosts. We hypothesise that interaction with environmental amoebae increases infectivity of M. bovis. In preliminary experiments to support this PhD project we showed that M. bovis actively escapes predation by the soil and dung-dwelling amoeba, Dictyostelium discoideum. It does this using the ESX-1 and ESX-5b type VII secretion systems as part of an extensive programme of mechanisms involving hundreds of genes.
In this project, the student will characterise how M. bovis changes its physiology during infection of Dictyostelium and establish if these changes pre-adapt the bacterium for mammalian infection, as is the case for other bacterial pathogens such as Legionella pneumophila, Vibrio cholerae and Salmonella enterica. Indeed, for Legionella the demonstration that passage through amoebae increased infectivity was critical to understanding the paradox that concentrations of Legionella below the experimentally determined infective dose were able to cause human infection. Thus, it is important that we understand the effect of amoeba passage on M. bovis physiology and how this affects infectivity. This fundamental biology could transform our understanding of bTB transmission and will help design measures to control environmental transmission of M. bovis in badgers and cattle. Specifically, the findings will guide validation of disinfection strategies for bTB breakdown farms with the potential to significantly impact persistence rates and infection of reintroduced cattle.
Please apply by submitting an application form and completing our EDI survey.
Project 5: Modelling the Role of Superspreaders in Disease Outbreaks
Theme(s): Understanding Disease Spread
Lead Partner: University of Surrey
Supervisor: Klara Wanelik, [email protected]
Joint Partner: DSTL
Supervisor: Thomas Laws, [email protected]
Project Summary Superspreaders are the minority of individuals responsible for the majority of disease spread and come in two forms. Supershedders spread more disease because they shed more pathogen. Supercontacters spread more disease because they have more social contacts. The presence of supershedders and/or supercontacters in a population is likely to be associated with distinctive patterns of disease spread which, if detected early, could be used to better design disease control strategies.
In this project, you will use a novel epidemiological modelling approach to simulate disease outbreaks in closed populations (representative of e.g. a military base or naval vessel) and to better understand the role of supershedders and/or supercontacters in driving patterns of disease spread. Your model will incorporate both within-host and between-host dynamics.
Project Objectives:
- In a scenario where there are only supershedders, identify which physiological features of supershedders (e.g. infectious period, pathogen load) impact on patterns of disease spread and how.
- In a scenario where there are only supercontacters, identify which behavioural features of supercontacters (e.g. contact frequency, contact duration, contact heterogeneity) impact on patterns of disease spread and how.
- In a more realistic scenario where there are supershedders and supercontacters, identify which features of supershedders and supercontacters impact on patterns of disease spread and how.
You will use openly available datasets for a representative range of viral pathogens to parameterise and test your model. This will include Ebola and Lassa virus – two major pathogens of strategic importance that exhibit contrasting dynamics.
This project is an exciting opportunity to contribute to preparedness for pathogen X, a pandemic pathogen that has not yet been characterised. It would suit those with an interest in infectious diseases, public health and/or epidemiological modelling. Experience in epidemiological modelling is desirable but not essential. The individual will work closely with Dstl.
Please apply by submitting an application form and completing our EDI survey.
Project 6: Exploring Gene Transfer and Recombination in Poxviruses Using AI and Pangenomics
Theme(s): Microbial Evolution and Drug Resistance; Understanding Disease Spread
Lead Partner: University of Surrey
Supervisor: Bingxin Lu, [email protected]
Joint Partner: Pirbright Institute
Supervisor: Tim Downing, [email protected]
Project Summary Poxviruses pose a major threat to human and livestock health, such as mpox, which remains a continuing threat. Poxviruses evolve through a combination of mutation, recombination, and gene transfer. These processes permit the exchange of new DNA segments, which may encode proteins with novel functions in new viral hosts, resulting in new outbreaks and epidemic threats. Moreover, high rates of rearrangements and repetitiveness in poxvirus genomes obscure the adaptation and origins of different lineages. Existing tools to study these processes were developed for prokaryotic or eukaryotic organisms and certain virus types, but none have been optimised for poxviruses. Additionally, we are now in a much better position to understand poxvirus adaptation, thanks to recent advances in extensive short- and long-read genome sequencing of human and livestock poxviruses. This means new inferences are possible, if appropriate scientific methods are used.
This project will explore published diverse poxvirus genomes using better gene transfer and recombination analysis. It will leverage two novel approaches: pangenome graphs and artificial intelligence-informed phylogenetics. We will use unsupervised machine learning methods based on DNA similarity and related pangenome graph information to identify regions of interest in individual virus genomes. This will be designed to identify gene transfer and recombination in new, unknown samples. Identified gene transfer and recombination events will be verified using phylogenetic methods and compared to the results of existing tools to validate and improve the new approaches.
This project will train you in cutting-edge methods (machine learning, genomics/pangenomics, and viral genetics) that will shed new light on gene transfer, recombination, and genomic diversity in poxviruses. It will create improved genome analysis methods for poxviruses to pin-point genes driving outbreaks with pandemic potential. This project will lay a foundation on which to explore virus evolution, and to apply these machine-learning and pangenomic tools to other viruses.
Please apply by submitting an application form and completing our EDI survey.
Project 7: Impact of Diabetes on Dengue Virus Transmission and Disease Severity
Theme(s): Infection and Cellular Biology; Understanding Disease Spread
Lead Partner: University of Surrey
Supervisor: Paola Campagnolo, [email protected]
Joint Partner: The Pirbright Institute
Supervisor: Kevin Maringer, [email protected]
Project Summary Dengue is the most significant mosquito-borne viral disease globally, affecting over half the world’s population across tropical and subtropical countries while also emerging in Europe, due to climate change. Over 80% of people living with diabetes reside in dengue-endemic countries. In coming decades, we expect a significant increase in the burden of both diseases. People living with diabetes are more likely to develop severe (haemorrhagic) dengue symptoms, yet our understanding of the role of diabetes in dengue virus transmission and disease severity is limited.
Our preliminary data suggest that dengue haemorrhage is exacerbated by dysfunctional interactions between microvascular cells (endothelial cells and pericytes) in people living with diabetes. The first aim of this project is to use RNA-Seq, proteomics, functional assays (angiogenesis and permeability assays) and novel 3D in vitro co-culture models (organoids, microfluidics) developed at Surrey to characterise the mechanisms underlying worsened vascular outcomes in diabetic dengue patients.
Our data also suggest that dengue virus readily infects vascular pericytes and (rarely) endothelial cells in vitro. The second aim will explore the impact of diabetic conditions on dengue virus replication and functional microvascular outcomes during infection in vitro in The Pirbright Institute’s high-containment facilities.
Finally, previous reports suggest that mosquitoes fed with high-glucose blood more readily transmit dengue virus. The third aim will explore potential roles for enhanced virus replication and diabetic blood-induced hyperpermeability in the mosquito midgut in enhancing dengue virus transmission.
Technical training: cell culture, in vitro 3D multicellular cardiovascular models, vascular function assays, omics analyses, high containment virus work (CL3), mosquito husbandry and transmission assays.
Impact: The studentship will explore an urgent understudied area in a world of increasing dengue and diabetes rates, both in the Global North and South, helping to elucidate cellular mechanisms leading to enhanced dengue virus transmission and disease severity.
Please apply by submitting an application form and completing our EDI survey.
Project 8: Metabolic and Proteomic Responses in Mosquitoes During Persistent Viral Infections
Theme(s): Infection and Cellular Biology; Understanding Disease Spread
Lead Partner: University of Surrey
Supervisor: Dr Matteo Barberis, [email protected]
Joint Partner: Pirbright Institute
Supervisor: Dr Naomi Forrester-Soto, [email protected]
Project Summary This project aims at gaining systematic and mechanistic insights into viral infections. Specifically, it is designed to understand the metabolic and proteomic response of persistent infections in mosquitoes through a systems Biology strategy that integrates multiple levels of –omics data with experimentation. Viruses that use invertebrates as part of their lifecycle include well-known viruses such as Dengue virus, Chikungunya virus, and yellow fever virus. Persistent viral infections do not result in pathological injury to their hosts, but the presence of the infection causes a metabolic burden, which can impact the host. This interaction is not well understood. However, we know that successful infection of mosquitoes is multi-factorial and the mosquito metabolism is an understudied aspect of this interaction. Our hypothesis is that mosquito metabolism, and its regulation from the proteome, is critical to sustaining persistent infections and that specific metabolites can be identified that provide an environment allowing for viral persistence.
The student will utilise a series of mutant viruses from highly attenuated to wild type that will enable us to interrogate the role of metabolism in determining whether the virus is able to establish a persistent infection. They will use a combination of in vitro and in silico approaches to generate and prepare samples for metabolomic and proteomic analyses, using the wild-type and mutant strains of Venezuelan equine encephalitis virus (VEEV). The metabolomic and proteomic data will be integrated and annotated onto biochemical maps, which will be analysed to identify metabolic/proteomic targets in different states of viral infection. The results will be verified by targeting some of these key targets as indicators during viral infections and testing the outcomes for various viruses. Outcomes from this project will help us understand the relationship between mosquitoes and persistent viruses and will inform novel targeting strategies for the control of important mosquito-borne viruses.
Please apply by submitting an application form and completing our EDI survey.
Project 9: Developing a 3D Porcine Spleen Model for African Swine Fever Virus Research
Theme(s): Infection and Cellular Biology
Lead Partner: University of Surrey
Supervisor: Dr Patrizia Camelliti, [email protected]
Joint Partner: Pirbright Institute
Supervisor: Dr Natacha Ogando, [email protected]
Project Summary Global pork supplies are threatened by African swine fever (ASF), a devastating disease affecting pigs and wild boar. The causative agent, ASF virus (ASFV) targets macrophages and replicates in lymphoid organs such as spleen. Understanding host-ASFV interactions is critical for the development of ASF vaccines and ASF resilient animals. Still, most studies have predominantly focused on 2D macrophage cultures, which inadequately capture the complexity of immune processes during infection. In contrast, cutting-edge 3D culture systems better mimic in vivo conditions, enabling the investigation of dynamic cell-cell and cell-pathogen interactions within host tissues. Moreover, 3D cultures provide a sustainable platform that reduces the use of animals in research.
This interdisciplinary project, in collaboration with Dr Priscilla Tng (ASF Vaccinology), aims to develop a porcine spleen-derived 3D model to study complex host immune responses during ASFV infection. Two complementary approaches will be explored to study the interface between innate and adaptive immunity: organotypic slices prepared from freshly isolated spleen, and 3D spheroids generated using spleen isolated cells. Then, established 3D models will be used to study host immune processes and immune cell dynamics modulated by multiple ASFV strains of varying virulence. The project will involve working in high containment facility, and cross-disciplinary training in tissue bioengineering-, virology, immunology and computational data analysis, which will be provided on site.
Importantly, this work will develop a sustainable and ethically responsible 3D spleen model platform applicable to different areas of host-pathogen research, disease modelling and pharmacology, spanning both veterinary and biomedical research fields. Furthermore, this project will provide a novel perspective on host immune responses to ASFV infection and potentially identify mechanisms that can lead to the development of ASF control strategies to improve livestock health and global food security.
Please apply by submitting an application form and completing our EDI survey.
Project 10: Environmental Drivers of Mosquito-Borne Disease Outbreaks
Theme(s): Understanding Disease Spread; Detection, Prevention and Intervention
Lead Partner: University of Surrey
Supervisor: Gianni Lo Iacono, [email protected]
Joint Partner: Pirbright Institute
Supervisor: Marion England, [email protected]
Project Summary Mosquitoes are among the deadliest animals on Earth, transmitting diseases that affect people, animals, and ecosystems. This challenge is intensifying with climate and land-use change. For example, the spread of tiger mosquitoes across Europe, introduced through the trade of used tyres and plants, has brought dengue and chikungunya to new regions. Rift Valley fever and West Nile virus are two major mosquito-borne diseases that cause periodic outbreaks with serious health and economic impacts. Although most common in sub-Saharan Africa, both are expanding their range as environmental conditions shift.
These diseases are tightly linked to environmental factors. Rainfall creates breeding sites, while temperature affects mosquito survival and development. Understanding these relationships can help predict when and where outbreaks might occur. Our team has successfully used environmental data to model gastrointestinal diseases, and we now aim to extend these methods to mosquito-borne infections, which are more complex, and more exciting, because transmission involves both mosquitoes and humans.
In this project, you will apply a novel epidemiological modelling approach to simulate disease outbreaks based on environmental data.
Objectives:
- Develop an agent-based model of a vector-borne disease influenced by environmental factors.
- Using the technique developed for gastrointestinal diseases, estimate the crude probability of detecting a case based on weather and land-use conditions.
- Improve the technique by explicitly incorporating mosquito-borne transmission. You will achieve this by allowing the probability model to retain a “memory” of past events and validating it with the agent-based model.
- Apply the validated model to real-world data.
You will use open datasets on Rift Valley fever and West Nile virus from endemic regions and explore potential disease risks under UK climate change scenarios. This exciting project suits students interested in infectious diseases, public health, data science, or modelling; prior experience in modelling is helpful but not essential.
Please apply by submitting an application form and completing our EDI survey.
Project 11: Interplay Between Avian Coronavirus and Avian Pathogenic Escherichia coli in Poultry
Theme(s): Microbial Evolution and Drug Resistance; Infection and Cellular Biology
Lead Partner: University of Surrey
Supervisor: Jai Mehat, [email protected]
Joint Partner: The Pirbright Institute
Supervisor: Dr Erica Bickerton, [email protected]
Project Summary The University of Surrey, in collaboration with The Pirbright Institute, are offering an exciting PhD opportunity to investigate the complex interplay between avian coronavirus infectious bronchitis virus (IBV) and Avian Pathogenic Escherichia coli (APEC) in poultry.
Project Background The poultry industry is vital for feeding a growing global population but faces significant challenges from infectious diseases. Co-infections with IBV and APEC represent a major threat, causing immune suppression and secondary infections that lead to systemic colibacillosis and economic losses. Available vaccines offer limited protection, reflecting both narrow strain coverage and limited insight into how IBV increases susceptibility to APEC infection. This project aims to close this knowledge gap by exploring the cooperative dynamics by which IBV enhances APEC colonisation and bacterial opportunism, and identify viral-bacterial strain combinations that lead to the most severe disease outcomes.
Approaches We will employ cutting-edge in vitro and ex vivo models to investigate the synergistic dynamics of IBV and APEC co-infection across key mucosal sites.
Using three-dimensional “inside-out” chicken enteroids incorporating a leukocyte component, we will explore how enterotropic IBV infection alters intestinal barrier integrity and promotes bacterial infiltration, using advanced microscopy approaches to visualise interactions in detail. Complementary high-resolution metagenomic analyses of IBV-infected chickens will identify virus-induced shifts in the gut microbiota that may enhance APEC colonisation and shedding. In parallel, studies of IBV-APEC interactions in the avian respiratory tract will determine how IBV infection facilitates extra-intestinal dissemination and increases susceptibility to APEC.
Impact and Career Opportunities This PhD opportunity offers the unique benefit of collaboration between the University of Surrey and The Pirbright Institute, creating a dynamic environment that bridges academic and applied science. This research will provide critical insights into viral-bacterial co-infections- a key challenge in One-Health contexts, paving the way for improved disease control strategies and reducing reliance on antimicrobials.
Please apply by submitting an application form and completing our EDI survey.
Project 12: Role of Post-Translational Modifications in Cross-Species Adaptation of Swine Vesicular Disease Virus
Theme(s): Infection and Cellular Biology
Lead Partner: University of Surrey
Supervisor: Samaneh Kouchaki, [email protected]
Joint Partner: The Pirbright Institute
Supervisor: James Kelly, [email protected]
Project Summary Post-translational modifications (PTMs), including phosphorylation, ubiquitination, and glycosylation, are crucial for viral functions like replication, capsid maturation, and evading the host immune system. PTMs can also be a key factor in cross-species transmission.
Host range of retroviruses like HIV is notably limited by species-specific variations of the antiviral protein TRIM5. TRIM5 acts by ubiquitinating the viral capsid, tagging it for destruction by the proteasome. However, retroviruses evolve to evade their native host’s TRIM5, while remaining susceptible to that of other species. For example, the cross-species jump of HIV from monkeys to humans, required HIV to adapt and bypass inactivation by human-specific TRIM5. This illustrates how PTMs can play a key role in cross-species transmission.
This interdisciplinary project will investigate the role of PTMs in the cross-species jump of swine vesicular disease virus (SVDV). An enterovirus that emerged from the human virus Coxsackievirus B5 (CVB5) through a human to pig species-jump in the 1960s. By leveraging cutting-edge AI and advanced molecular virology we will pinpoint the PTMs crucial for viral adaptation to new species.
Phase 1: Identification of PTMs using cutting-edge AI models At the Surrey Institute for People-Centred AI, CVSSP, and School of Health Sciences (supervised by Samaneh Kouchaki and Ayse Demirkan), the student will develop AI-driven PTM prediction models using mass-spectrometry proteomics, and structural modelling to identify key PTMs. This will reveal how the PTM landscape of CVB5/SVDV was reshaped by its 60-year evolution in pigs.
Phase 2: Characterisation of PTMs through in vitro and live virus studies Working in high-containment labs at the world-leading Pirbright Institute, the student will investigate how PTMs shape the enterovirus life cycle and control host-specificity of CVB5/SVDV.
This research will reveal mechanisms underlying cross-species adaptation in enteroviruses and provide new insights for rational antiviral design and zoonotic risk assessment across human and animal health.
Please apply by submitting an application form and completing our EDI survey.
Project 13: Characterising Novel Virus-Induced Cytoplasmic Complexes in Herpesviruses
Theme(s): Infection and Cellular Biology
Lead Partner: University of Surrey
Supervisor: Gill Elliott, [email protected]
Joint Partner: The Pirbright Institute
Supervisor: Nicolas Locker, [email protected]
Project Summary Many viruses induce the formation of novel membraneless biocondensates which are involved in a range of processes including genome replication, virus assembly and inhibition of immune responses. We have discovered a novel biocondensate that is induced in the cytoplasm of herpes simplex virus infected cells which we have termed virus-induced cytoplasmic complexes (VICCs). These structures are induced later in infection and contain at least one virus protein specifically targeted there (VICC-protein). Nonetheless, their role in virus infection remains unknown. In this exciting project, you will train across an interdisciplinary team of three research-active groups where you will learn a wide range of skills and cutting-edge technology to address the purpose and nature of these novel VICC biocondensates.
In the Elliott group (University of Surrey), you will utilise HSV1 expressing a GFP-tagged VICC-protein in a range of virological and bioimaging experiments (eg confocal, live-cell, and super-resolution microscopy) to investigate the cell biology, kinetics and dynamics of VICC assembly and determine their contribution to efficient virus production and/or regulation of innate immune responses. Methodology to purify VICCs will be developed in the Locker group (Pirbright Institute) in collaboration with the SEISMIC facility (Kings College London), leveraging biochemical and in situ dissection processes to isolate and determine the viral and cellular proteome of VICCs. Compositional analysis of these structures will subsequently inform parallel virological studies. To assess if VICCs are a panviral feature of alphaherpesviruses, animal herpesviruses that express homologues of the VICC-protein will be engineered to express GFP-tagged protein, and VICC formation examined by microscopy.
By defining these new virus-induced structures across the alphaherpesvirus family, you will make a vital contribution to current understanding of the herpesvirus-host cell relationship and establish the potential for VICCs to be exploited as a new panviral target for herpesvirus infection in humans and animals.
Please apply by submitting an application form and completing our EDI survey.
Project 14: Developing Rapid Diagnostics for Tuberculosis and Non-Tuberculous Mycobacteria
Theme(s): Detection, Prevention and Intervention
Lead Partner: University of Surrey
Supervisor: Suzie Hingley-Wilson, [email protected]
Joint Partner: UKHSA
Supervisor: Ginny Moore, [email protected]
Case Supervisor: Jessie Carpenter, [email protected]
Project Summary Tuberculosis (TB) is often called the forgotten pandemic, causing over 1.3 million deaths every year. Much of this burden is in West Africa, where many of the TB-causing strains are not the usual suspect Mycobacterium tuberculosis (Mtb). Up to 50% of TB cases may be misdiagnosed, with many caused by other lineages of the Mycobacterium tuberculosis complex (MTBC) or by non-tuberculous mycobacteria (NTM), such as Mycobacterium abscessus (MABC). Research from our lab also revealed a high proportion of mixed MTBC infections and potential non-tuberculous mycobacteria (NTM) causing TB (Owusu et al., 2022). Treatment for Mtb, MTBCs and NTMs differs significantly, and misapplication of these treatments can lead to exacerbation of existing infections or complete treatment failure.
This PhD project will help with misdiagnosis and improve treatment prescribing, by developing and validating a cutting-edge diagnostic test to differentiate NTMs and MTBC strains using our industrial partner VIDIIA’s rapid AI-assisted diagnostics. The test will focus on MTBC’s and clinically relevant NTMs, such as M. abscessus. Many NTMs are ubiquitous in the environment and their presence in hospital water systems can be associated with calamitous outbreaks. Therefore, this diagnostic test will be adapted to be of use in patient and environmental samples. Initially, cutting edge bioinformatics will be used to further develop the differentiative test to define the loop mediated isothermal amplification (LAMP) or Clustered regularly interspaced short palindromic repeats (CRISPR) primers. Environmental diagnostics will be tested at UKHSA using their “model” hospital ward, before testing on real-life samples in the UK and in Ghana.
This project could help save lives by enabling accurate and rapid diagnosis in high-burden areas, breaking the cycle of treatment failure, AMR, and disease transmission. Students will gain valuable experience in bioinformatics, molecular diagnostics and translational science, while contributing to a project with real-world impact on global health.
Please apply by submitting an application form and completing our EDI survey.
Project 15: Targeting ADAMTS Metalloproteinases for Treatment of Respiratory Viral Infections
Theme(s): Detection, Prevention and Intervention; Infection and Cellular Biology
Lead Partner: University of Surrey
Supervisor: Salvatore Santamaria, [email protected]
Joint Partner: UKHSA
Supervisor: Anika Singanayagam, [email protected]
Project Summary Upper respiratory tract infections are the leading cause of acute disease worldwide causing over 12 billion episodes each year. Seasonal respiratory viruses, including influenza and respiratory syncytial virus (RSV), drive major morbidity and mortality despite the use of current vaccines and antivirals that target the pathogen. There is an unmet need for treatments that, in contrast to currently available prophylactics/interventions, do not require annual reformulation or close monitoring of mutations. Therapeutics targeting the host response, a conserved mechanism of defence during viral infections, may provide an universal weapon in the arms race against respiratory viruses. Extracellular matrix (ECM)-associated metalloproteinases called ADAMTSs are emerging as regulators of antiviral immunity: genetic manipulation of ADAMTS4 or ADAMTS5 improves survival following influenza infection of mice, yet the mechanistic basis of this immune regulation is unresolved.
We hypothesise that pharmacologic inhibition of ADAMTS paralogues may improve survival after lung viral infection by reprograming host responses and limiting damaging inflammation.
By leveraging selective anti-ADAMTS4 and ADAMTS5 monoclonal antibodies (mAbs), we will dissect protease-dependent control of virus-host interactions in advanced cellular models and translational assays to accelerate preclinical development.
We have already generated 1) a mAb blocking ADAMTS4 activity; 2) a mAb that increases extracellular ADAMTS5 levels by blocking ADAMTS5 internalisation into the cells and subsequent degradation. Both antibodies demonstrated efficacy in ex-vivo models of osteoarthritis. In this project, we aim to repurpose anti-ADAMTS mAbs and assess their feasibility as treatments for viral lung infections by achieving three specific aims:
- Reformatting, expression and purification of humanised anti-ADAMTS and anti-ADAMTS5 mAbs.
- Assessing the effect of anti-ADAMTS mAbs on cell lines and primary cells infected with RSV and influenza virus.
- Understanding the impact of ADAMTS mAbs on the innate immune responses to respiratory viral infection and subsequent disease.
Please apply by submitting an application form and completing our EDI survey.
Project 16: Harnessing Lactic Acid Bacteria for Antiviral Responses in Pigs
Theme(s): Infection and Cellular Biology
Lead Partner: University of Surrey
Supervisor: Dr David J Allen, [email protected]
Joint Partner: UKHSA
Supervisor: Dr Alex Stewart, [email protected]
Project Summary Virus infections of pigs have a global economic impact of billions of dollars annually. Alongside affecting animal health directly, they cause secondary bacterial coinfections driving antibiotic use, contributing to AMR, and indirectly affect human health through impacting food security and livelihoods through losses. Endemic and emerging viruses in pig populations include flaviviruses, picornaviruses, nidoviruses and parvoviruses.
Understanding virus-host interactions such as immune responses mediated by type-I interferons (IFN-I) that initiate antiviral responses are underexplored as pathways to developing countermeasures.
Early virus-host interactions do not occur in isolation: sites targeted by viruses have populations of resident commensal bacteria (‘microbiota’) which can modulate immune responses. Lactic acid bacteria (LAB) – common beneficial commensals – activate IFN-I responses via intracellular sensors STING and MAVS which are important components of signalling systems that initiate IFN-I antiviral responses to DNA and RNA viruses, respectively.
Therefore: can LAB trigger an antiviral response for therapeutic use?
The project will answer this question through three objectives:
- Build cell-based laboratory models for measuring IFN-I responses following infection with RNA/DNA viruses, in the presence/absence of LAB, and with/without STING or MAVS.
- Determine components of LAB critical for the activation of STING or MAVS, and characterise IFN-antagonistic viral proteins in these systems.
- Test LAB – or LAB components – against a panel of viruses to demonstrate their potential as a therapeutic.
The project provides training in laboratory techniques, including CRISPR, RNA knockdown/out, stable cell line production, molecular biology, quantitative RT-PCR, sequencing, protein-protein interaction assays, bacterial culture, recombinant protein expression, cell transfection, and virus/cell culture, and working with APHA who have collections of porcine viruses for study in laboratory and in vivo challenge systems.
This one-health research will establish potential for use of LAB as a probiotic, and/or identify components of LAB for development as therapeutics, to control viral infections in pig herds.
Please apply by submitting an application form and completing our EDI survey.
Project 17: Evaluating Immunomodulatory Agents in Human Immune Organoids for Anti-Viral Immunity
Theme(s): Infection and Cellular Biology; Detection, Prevention and Intervention
Lead Partner: University of Surrey
Supervisor: Dr Qibo Zhang, [email protected]
Joint Partner: UKHSA
Supervisor: Dr Julie Tree, [email protected]
Project Summary Rationale Immunity against virus infection critically depend on T cell and antibody responses produced in the immune system. Development of immunomodulatory agents/drugs to enhance these immune responses is an important strategy for better efficacy of treatment such as antibody-based or anti-viral therapy. Testing of new drugs typically involves the use of animal models to generate pre-clinical data. There is a growing momentum to replace/reduce animal experimentation. The availability of complex in vitro models such as human organoid system may provide experimental data that better predict clinical outcomes in humans. This PhD project aims to evaluate the effectiveness of new immunomodulatory agents and antivirals in anti-viral immunity using human tissue-derived immune organoids.
Approaches Using an in vitro immune organoid culture system established in Dr Zhang’s lab, which is based on immune tissue/cells from children & adults and able to study immune responses to microbial infection and vaccines, this project will characterise/evaluate the effectiveness of immunomodulatory agents and antivirals on enhancement of anti-viral response. Both T cell- and antibody-mediated immunity to influenza A(H1N1) (a prototype of highly pathogenic avian influenza virus), SARS-CoV-2 and Herpes simplex virus(HSV) will be analysed. CD4/CD8 T cell responses, cytokine profiles, and antibody responses induced by the virus antigens, with/without immunomodulatory agents (e.g. TLR4, TLR7/8 agonists, IFNβ) will be evaluated, using state-of-the-art techniques including confocal microscopy, flowcytometry, immunoassays and virus neutralisation analysis (within Biosafety Level 3 facilities).
The PhD student will be jointly supervised by multidisciplinary teams at UoS (Dr Zhang and Prof Elliot) and UKHSA (Drs Tree and Horton), with expertise/experience in immunology, anti-viral drug testing and viral infection biology.
Impact An in vitro immune organoid system with capacities for testing immunotherapeutic anti-viral agents and better predicting clinical outcomes will speed up development of effective anti-viral drugs for humans and improve pandemic preparedness against new virus infection.
Please apply by submitting an application form and completing our EDI survey.
Project 18: Molecular and Immune Mechanisms of Rift Valley Fever Virus Pathology
Theme(s): Detection, Prevention and Intervention; Understanding Disease Spread
Lead Partner: University of Surrey
Supervisor: Lisa Holbrook, [email protected]
Joint Partner: UKHSA
Supervisor: Stuart Dowall, [email protected]
Collaborative Partner: The Pirbright Institute
Project Summary Rift Valley fever virus (RVFV) is a mosquito-transmitted, zoonotic, emerging bunyavirus categorised by the World Health Organisation (WHO) as a high-consequence, priority pathogen due to its emergence and lack of effective treatments. It can cause viral haemorrhagic fever in humans and livestock characterised by necrotic lesions in major organs, decreased circulation of platelets, coagulation defects and increased vascular permeability resulting in oedema, hypotension, shock, and in severe cases, death. How RVFV induces pathology remains largely unknown and understanding the molecular and immune mechanisms underlying RVFV infection and pathology will identify new avenues for therapeutics development.
Haemorrhagic fever-inducing viruses, including RVFV, cause destruction or dysfunction of platelets. Platelets are essential in haemostasis, for integrity of the vascular system and immunity. They can be activated aberrantly by interaction with viruses or virus-infected cells, causing them to adhere to the endothelium. We hypothesise that RVFV-activated platelets adhere to endothelial cells, altering their function, increasing vascular permeability and reducing the circulating platelet number leading to haemorrhage. Treatments that prevent or correct this platelet loss and dysfunction in RVFV infection have the potential to ameliorate platelet-mediated pathology and to significantly improve clinical outcome.
Supervised by Dr Lisa Holbrook (University of Surrey), Dr Stuart Dowall (UKHSA) and Dr Naomi Forrester-Soto (Pirbright Institute), this project will examine the molecular and immune interactions between RVFV, platelets and the endothelium and explore how these lead to pathology by characterising the mode of RVFV-induced platelet activation, platelet dysfunction and changes to endothelial permeability using a combination of in vitro and in vivo methods. Final confirmation of in vitro mechanisms will be evaluated using material from RVFV challenge animal models allowing direct comparison with disease severity and clinical outcome.
This interdisciplinary project will provide training in platelet biology alongside high containment virology, in vivo models, molecular and cell biology assays.
Please apply by submitting an application form and completing our EDI survey.
