One Health

One Health

We are seeking outstanding PhD candidates for University of Edinburgh and University of Glasgow Joint PhD Studentships below:

The vision for this theme is to shape the future practice of combined animal and human health management through partnerships across disciplines and institutions.

One Health can be interpreted widely, but in the context of this studentship programme we focus on the design, implementation and evaluation of interventions in the management of animal populations for the primary purpose of controlling zoonotic disease and improving human health. Such interventions will focus around the development and use of vaccines, drugs, genome editing for resilience, behaviour or husbandry practices, market economics or combinations thereof. 

Projects will highlight the critical importance of social science in leading, designing, planning, implementing and evaluating One Health interventions – including both qualitative (e.g. ethnographic research) and quantitative (e.g. behavioural economics) approaches. We also recognise an important role for fundamental research in understanding the epidemiology of zoonotic pathogens including anti-microbial resistant (AMR) bacteria (e.g. the transformative contributions pathogen genomics has made to understanding transmission). We encourage multi-disciplinary projects that generate knowledge relevant to the design, validation or improvement of interventions in animals for the control of zoonotic disease, and the benefit of human health.

The joint studentship programme will build on existing platforms and synergies within and between our respective institution. For example, Edinburgh Infectious Disease (EID) comprises 190 different research groups across the University and neighbouring institutions interested in infectious disease research. Of note, at the University of Edinburgh, the medical and veterinary schools and the Roslin Institute work closely together within the same College (CMVM), and additional expertise and facilities are available in the School of Biological Sciences, and in Social Science in the College of Arts Humanities and Social Science (CAHSS). Further support for ‘One Health’ Science in the University of Edinburgh comes from the Global Academy for Agriculture and Food Security, The Center for Tropical Livestock Genetics and Health, and the Center for Biomedicine, Self and Society.

‘One Health’ is one of the University’s six Research Beacons, with research supported across the Colleges of Medical, Veterinary and Life Sciences, and Social Sciences, and through interdisciplinary structures including the award-winning Boyd Orr Centre for Population and Ecosystem Health, the MRC Centre for Virus Research, the Wellcome-Trust-funded Centre for Molecular Parasitology, the Institute for Health and Wellbeing and the MRC/CSO Social and Public Health Sciences Unit.

Students will also take advantage of the existing joint collaborative projects such as the Gates-funded Centre for Supporting Evidence-Based Interventions (SEBI), Epidemiology, Population health and Infectious disease Control (EPIC), and established interactions with key organisations such as GALVmed.

How to Apply

1) Prospective students should review the list of potential projects proposals and queries regarding eligibility can be directed to cahsspg.awards@ed.ac.uk (University of Edinburgh) or pgr@glasgow.ac.uk (University of Glasgow) .

2) Applicants should register their details online. Please note that this is not an application to study at the respective universities.

3) Unless otherwise stated, applicants may submit applications, via email to pgr@glasgow.ac.uk, up until the application deadline of 5.00pm, Monday 21 January 2019.  

Required documentation should be submitted as a combined PDF document using the file name '<Theme>, <Applicant First name Surname> ie 'One Health, Phillipa Dean':

University of Glasgow Led Projects

University of Glasgow Led Projects

Leveraging pathogen genomics and phylodynamics to control endemic anthrax

Project Description:

Recent advances in sequencing technology have revolutionised our ability to track infectious disease dynamics using pathogen genomes, such as during outbreak investigations. However, these tools remain underutilised for addressing endemic disease threats, especially those affecting human and animal health in low-resource settings.  

Anthrax is a classic example of a neglected bacterial zoonosis, affecting marginalised communities in many parts of the global south, including much of Sub-Saharan Africa. It causes significant mortality in people as well as livestock losses, but tends to be undiagnosed and underreported. Although vaccination of livestock plays a key role in preventing infection in both people and animals, it is often not affordable. Moreover, because the spores of the anthrax bacterium Bacillus anthracis can remain infectious within the environment for decades, it is not clear how long livestock vaccination would have to be maintained before a measurable reduction in infection risk is achieved. Obtaining genome data from detected cases, and incorporating genomic and epidemiological data into phylodynamic models provide a novel and powerful means to track residual anthrax transmission and quantify progress towards its elimination.

This project aims to create the necessary framework for guiding anthrax control programmes in endemic settings through the use of pathogen genomics and phylodynamic modelling. Building on robust partnerships and research platforms established in northern Tanzania by the Glasgow supervisors, including existing genomic data, our project will:

1) Extend current analytical tools and molecular clock models to accommodate the alternation between extended environmental persistence and periodic rapid replication typical for B. anthracis

2) Develop a simulation model combining genomic, spatial, temporal and epidemiological information to examine the effect of vaccination on B. anthracis genetic diversity and transmission in silico

Validate this model by generating genomic data obtained during a livestock vaccination program expected to start in the study area in 2019.

 

Supervisors:


Self-spreading Interventions to Prevent Viral Spillover from Bats to Humans and Domestic Animals

Project Description:

A new generation of self-spreading, virally-vectored vaccines promises new opportunities to limit disease transmission within otherwise intractable wildlife sources of human and domestic animal disease. However, since sustained transmission of engineered viral vectors poses difficult to foresee biological risks, finding ‘minimally transmissible’ vaccines that are adequate for disease management goals is a major research need.

This project uses a data-rich and economically important system, vampire bat rabies in Latin America, to develop an epidemiological framework for applying virally-vectored vaccines to bats, a key wildlife reservoir for emerging viruses. We develop our framework based on two extremes in vaccine transmission: a vampire bat Betaherpesvirus, identified in our recent work as a potentially fully transmissible vector that is expected to cause a lifelong recurrent infection and an existing poxvirus vector, which spreads only from topically treated bats to untreated bats by grooming and contact and is rapidly cleared. Field experiments in wild vampire bat colonies in Peru will project the spread of viral vectors following initial release using UV powders to measure contact and Rhodamine b to measure consumption. We will estimate the prevalence of natural Betaherpesvirus and of natural poxviruses that may interfere with engineered vectors through cross-immunity and the frequency of Betaherpesvirus shedding using field monitoring and PCR. Sequencing and phylogenetic analyses of Betaherpesviruses will trace and project the potential inter-colony spread of introduced vaccines. Finally, existing mathematical models of rabies within vampire bat populations will be adapted to incorporate vaccines with varying levels of capacity for spread. This will allow us to develop strategies that target either reducing infections in livestock and humans or regional elimination of rabies from bats and to assess how release strategies depend on vaccine vector choice.

Supervisors:


Genetic and mathematical dissection of the mechanisms of antigenic variation in Trypanosoma congolense

Project Description:

Diversity is fundamental to biological processes at all scales. One area in which measuring diversity is critical, and where quantification has wide application, is in host-pathogen interaction. A central pathogen reaction to counter the host acquired immune response is termed antigenic variation, which involves the dynamic expression of surface antigens, allowing for long term infection, transmission and super-infection. African trypanosomes are an exemplar of pathogen antigenic variation, with extensive data in Trypanosoma brucei having detailed the recombination reactions that mediate ‘switching’ of the Variant Surface Glycoprotein (VSGs), as well as RNA studies that have detailed the extent of expressed VSG diversity in mice infections. It is widely assumed that these findings in T. brucei, which causes human trypanosomiasis, applies also to T. conglense and T. vivax, which cause animal trypanosomiasis. However, recent genome sequencing efforts have suggested the recombination processes that have shaped the archive of VSG genes differ in the three trypanosomes, and that the nature of T. congolense VSG transcription may differ from the well charactarised system of VSG ‘expression sites’ used by T. brucei. Thus, it is important to begin to dissect the mechanism of VSG switching in T. congolense, and to evaluate VSG diversity during infections. We and others have recently demonstrated that it is possible to genetically modify T. congolense and, as result, we propose in this PhD project to generate mutants in two key T. congolense recombination genes, RAD51 and BRCA2. We will then establish infections with the mutant parasites and measure VSG expressed diversity using RNAseq, and examine the stability of the VSG archive by genome sequencing, comparing with wild type parasites. In so doing, we will determine if and how recombination drives VSG switching in T. congolense, and whether or not loss of these factors alters the VSG archive. All the data generated will then be compared with similar, ongoing experiments in T. brucei, allowing us to ask, for the first time, if the dynamics and mechanisms of VSG switching are the same or different in trypanosome species that cause human and animal trypanosomiasis. As human animal trypanosomiasis is the focus of concerted WHO-led efforts at eradication, this project will ask if these efforts might also be applicable to animal trypanosomiasis, which is not currently being tackled directly and therefore remains a major threat in Africa and beyond.

 

Supervisors:

 


Antimicrobial quality, use, access, and demand in rural African communities (QUAD-Africa)

Project Description:

Antimicrobial resistance (AMR) threatens human and animal health, productivity and prosperity, with the greatest impacts falling on Low Income Countries. East Africa has considerable gaps in AMR research despite the prevalence of the problem, particularly in livestock-dependent communities. Certain local practices in these communities may trigger AMR in people and animals, including preventative use of antibiotics administered by livestock owners to themselves and their animals without clinical and diagnostic assessment. Such widespread self-medication practices combined with accessibility to counterfeit drugs with sub-therapeutic antimicrobials could represent important sources of AMR. Yet, these processes remain poorly understood.

Focusing on traditional livestock-keeping systems in rural Tanzania, this project will investigate access to, and use and quality of human and veterinary drugs as well as their respective drivers. Such communities, who lack antimicrobial stewardship strategies with disproportionately high risk of infection, are particularly important in highlighting potentially extreme impacts of resistance to clinically-relevant antibiotics. The PhD research links into a large MRC-funded consortium tackling AMR in Tanzania the UG supervisors are investigators on. The consortium provides essential information on local understanding and behaviours around health, illness, and antimicrobial use and resistance, and a critical field platform to map baseline antimicrobial QUAD dynamics in rural communities. Further surveys will map the supply chain down up to the users (i.e. community residents seeking medical or veterinary care) both through formal (e.g. dispensaries and licensed drug suppliers) and informal (e.g. local healers, market/black market sellers of bio/traditional medicines, and interpersonal exchange of curatives) channels. Furthermore, pharmacological assessments of antibacterial quality through the identified local networks will reveal their antimicrobial activity or lack thereof.

Ultimately, this project will assess the quality, access and supply as well as usage of antimicrobials in a resource-limited setting towards identifying local and regional challenges as well as solutions for antimicrobial stewardship.

 

Supervisors:


Coordination on networks for livestock disease control: a one health approach.

Project Description:

Farming sustainability and a healthy livestock system is critical for food security and the health of human society more broadly. Better understanding of how cooperative behavior amongst farms can be used to simultaneously reduce livestock disease burden and improve productivity will lead to both improved animal health and greater food security, as well as providing general insights into the role of human behavior in sustainability of agricultural systems.

In this PhD, we will use an integrated epi-economic modelling approach to develop new understandings of the process of infectious livestock disease transmission, and of the role of human, policy and market responses to reducing disease risk across an epi-system.

The student will develop a conceptual epi-economic model of an infectious livestock disease. This model will include the ideas of (1) shiftable externalities between farmers and (2) coordination games on a network. Both (1) and (2) can be shown to lead to too little spending by farmers on infectious disease control. With regard to (1), the work will build on the theoretical model of Fenichel et al (ERE, 2014) which shows that the critical feature is whether private disease risk control actions are strategic complements or strategic substitutes. With regard to (2), we will build on the literature on spatial coordination in Payment for Ecosystem Service schemes, using the idea of an Agglomeration Bonus. This is a 2-part incentive scheme which creates a coordination game between players (farmers) on a network. The student will use this model to compare the performance of an Agglomeration Bonus-type scheme to incentivise higher on-farm biosecurity investments with a market price-led scheme, where livestock markets reward lower risk sellers with higher prices.

 

Supervisors:


An Interdisciplinary Approach to Intersectoral Surveillance

Project Description:

Integrated Bite Case Management (IBCM) is a One Health approach for intersectoral surveillance that is recommended as part of the global strategy to eliminate human deaths from dog-mediated rabies ‘Zero by 30’. IBCM involves risk assessments by health workers to identify high-risk bites, to trigger epidemiological investigations by veterinary officers for detection of rabies cases, and to formalize intersectoral communication channels to guide appropriate and coordinated prevention and control. IBCM is crucial to the rabies endgame when enhanced surveillance is needed to respond effectively to incursions and ultimately to verify and maintain freedom from disease.

The Philippines has made considerable progress towards rabies elimination. Mass dog vaccination is underway across much of the country, however incursions and outbreaks continue. Improved access to lifesaving human rabies vaccines has reduced mortality but proven expensive.  More sustainable approaches to elimination are urgently needed. This studentship is part of a larger operational study of intersectoral surveillance in the Philippines aiming to accelerate achievement of rabies freedom and ensure sustainability of the national rabies control programme.

Using mixed methods, the student will examine the feasibility, acceptability and effectiveness of IBCM, collecting data on barriers and facilitators to deploying this approach as part of an embedded process evaluation. The student will conduct semi-ethnographic research working with local frontline veterinary and health workers and will co-produce guidelines for replication and scale-up of strengthened intersectoral surveillance. 

The ultimate project aim is to generate transferrable lessons for best practice for One Health surveillance and specifically for rabies elimination. Further opportunities would include engagement with rabies technical support programmes in the region through the UN Food and Agriculture Organization and other international partners (the world organization for Animal Health and the US Centers for Disease Control and Prevention).

Supervisors:


University of Edinburgh Led Projects

University of Edinburgh Led Projects

Cost-effective Mitigation of Antimicrobial Use and Antimicrobial Resistance

Project Desrciption:

This project will identify cost-effective methods to reduce antimicrobial (AM) use and deliver technical and economic evidence to industrial stakeholders and governments to develop stewardship strategies to increase uptake of AM alternatives. 

Background: Antimicrobial resistance is a quintessential One Health challenge, with recognized public externality characteristics, and an absence of any global regulatory or governance architecture. Numerous national and international strategies and action plans have aimed to improve stewardship of medically important drugs and to reduce their use, especially in food-producing animals, but few of these suggest clear frameworks to evaluate interventions. This project will focus on the application of a marginal abatement cost curve (MACC) approach to illustrate the technical, economic and behavioural feasibility of key interventions applicable to antimicrobial use, thereby reducing a driver of resistance selection. The MACC approach has been successfully developed in the context of diffuse pollution control (e.g. greenhouse emissions from agriculture); in the context of AMR it will provide a novel framework for data collection, research and policy on key mitiation measures in farm production systems.

Key research questions:

1) What metrics are best used to express the effectiveness of AMR reduction across different livestock sectors?

2) What farm and supply chain measures are effective in reducing the use of antimicrobials/antibiotics in UK agriculture?

3) Which measures are most cost-effective and likely to be implemented?

4) What are the behavioural challenges specific to each cost-effective meaure?

5)Which market-based and policy instruments apply to each measure?

Training: A comprehensive training programme will be provided comprising both specialist scientific training and generic transferable and professional skills. The latter includes environmental economics, modelling, programming, geo-processing tools and introduction to epidemiology; e.g. ArcGIS and data statistical, using R scripts.

Supervisors:


Modelling Bovine Tuberculosis Epidemiology and Zoonotic Risk in Tanzania

Project Description:

Zoonotic tuberculosis, caused primarily by Mycobacterium bovis (bovine tuberculosis, bTB) is a global disease problem, causing an estimated 147,000 new cases and 12,500 deaths globally due to the disease in 2016. Furthermore, new concerns are emerging in relation to potential risks arising from intensification of dairy production across East Africa, with the potential for an industry-driven, continent wide zTB epidemic. Dairy production is being encouraged among smallholders providing a route out of poverty and improving nutrition. However, consumption of raw milk products can act as a major source of human infection.  In Cameroon, for example, 25% in dairy smallholder cattle were test positive, and one pastoralist herd 68% of cattle tested positive, however, the overall prevalence is thought to be much lower.  In Asia, where the dairy industry is more extensive, much higher prevalence’s of bTB and zTB have been reported, with 10-12% zTB rates in some human populations. Similarly, in Ethiopia recent studies indicate an increasing prevalence of infection within the developing dairy sector.

This PhD would address: (1) is the trajectory of cattle rearing in Tanzania consistent with the development of an industry-driven zTB epidemic; (2) what is the resultant impact of bTB spilling over into pastoralist cattle populations; and (3) what is the implication for the risks from milk consumption and how can they be mitigated without pricing milk out of reach of poor families?

The student will use extant data generated from funded projects that: (i) describe the demographics of livestock populations in northern Tanzania and socio-demographics of keepers, considering traditional pastoralist and more dairy-intensive agro-pastoralist industry sectors (tinyurl.com/SEEDZproject); (ii) generate a detailed picture of the smallholder sector (BMGF ADGG/CTLGH project) including measures of bTB prevalence. By projecting from observed bTB outbreak patterns and current demographics, the student will explore plausible future scenarios, using model-based analyses to identify which of these futures is more likely to generate increased zTB risks.

Supervisors:


Role of Metabolism-related Islets in Salmonella Pathogenesis

Project Description:

Salmonella is an animal and zoonotic pathogen of global importance. An estimated 78 million cases of human nontyphoidal salmonellosis occur annually and are frequently acquired via the food chain from farmed animals. Enteric and systemic salmonellosis also constrains animal productivity and welfare. A need exists for more effective vaccines to control Salmonella in livestock. Toward this aim, we have used transposon-directed insertion-site sequencing to assign roles to thousands of Salmonella enterica serovar Typhimurium genes in intestinal colonisation of chickens, pigs and cattle [1]. Moreover, we have used novel surgical methods to assign spatiotemporal roles to Salmonella genes during systemic translocation in cattle. These studies identified a core subset of genes that play conserved roles across species, but also identified host- and niche-specific virulence factors. Many attenuating mutations are located in islets of metabolism-related genes of poorly defined function. Variation in metabolism-related genes has also been associated with the host tropism and invasive potential of Salmonella. Here we propose to:

  1. Generate mutations in metabolism-related islets implicated in Salmonella pathogenesis.
  2. Define the impact of such mutations on the metabolome of Salmonella by mass spectrometry.
  3. Characterise mutant phenotypes in vitro, for example in relation to use of specific metabolites and using cell-based assays of virulence-associated phenotypes.
  4. Use novel 3R methods to assign phenotypes to mutants in farm animals, for example using ligated intestinal loop models to quantify net replication, inflammation and secretory responses.
  5. Use computational approaches to study the relationship between metabolism-related islets and the differential tropism and virulence of S. Typhimurium pathovariants and S. enterica serovars. 

The project will instil training in diverse areas and harness expertise, datasets and techniques in both partner institutions.

[1] Chaudhuri RR et al. 2013. Comprehensive assignment of roles for Salmonella Typhimurium genes in intestinal colonization of food-producing animals. PLoS Genetics 9:e1003456.

Supervisors:


How are Phage Infection Dynamics Altered by Bacterial Interactions with Eukaryotic Host Cells

Project Description:

Alternative treatments for life-threatening antimicrobial resistant infections are urgently required. Phage therapy, the use of bacteriophages to kill infecting bacteria, has real potential but has to overcome a number of barriers before its adoption in clinical settings. This PhD research will study bacterium-phage interactions on hosts cells and tissues to understand how bacteria avoid phage predation under realistic host conditions.  This project will study multi-drug resistant Escherichia coli associated with urinary tract infections (UTI).  Both humans and dogs can suffer from chronic UTIs caused by E. coli that can lead to life-threatening bacteraemia. 

Bladder cell lines and canine bladder organoid cultures infected with E. coli will be used to image and quantify phage interactions.  Bacteria will be fluorescently-labelled using in-house techniques and phage labelled using a CRISPR-Cas system.  Real time interactions will be captured using fluorescence and confocal microscopy.  The project will then identify E. coli genes important for resistance to phage predation under these ‘close to host’ conditions. This will start with genes already identified in a recent mutagenesis study1 and further screens may be required. The expression and role of specific genes will be studied using reporter fusions and site-directed mutants.  Ultimately, this work will feed into our bioinformatic pipelines to predict effective phage combinations for treatment.   

1 https://mbio.asm.org/content/9/4/e00705-18

Supervisors:


Application of a Metabolomic Approach to Studying Cellular Processes in Trypanosoma Vivax

Project Description:

Trypanosomiasis is a vector-borne disease of humans and animals. While the human disease is a rare success story (<2,500 cases in 2017), Animal African Trypanosomiasis (AAT) remains a significant problem, causing ~70 million infections and 3 million deaths per year in cattle. Most trypanosome research has focused on the species that causes human disease (Trypanosoma brucei), but AAT is mainly caused by two very different species, Trypanosoma congolense and Trypanosoma vivax. We are starting to understand that the significant genomic differences between these three species relate to fundamental differences in important phenotypes in AAT infection biology, such as pathogenesis, antigenic variation and metabolism. While progress is being made in T. congolense, we still know very little about these processes in T. vivax. T. vivax is the most evolutionary ancient of the African trypanosomes, and as well as being transmitted by the cyclical tsetse vector, has adapted to mechanical transmission and has spread beyond Africa to become an established livestock pathogen in South America. This project aims to characterize the key features of central carbon metabolism in T. vivax, using approaches that the supervisory team has successfully applied to T. brucei and T. congolense. The student will generate metabolomics and RNAseq datasets from parasites grown in vivo and ex vivo in order to identify key aspects of metabolism in T. vivax, andidentify metabolic processes for which T. vivax differs from T. congolense and T. brucei. This will include the selection and generation of drug resistant T. vivax in order to identify mechanisms of drug uptake and resistance. Identifying metabolic differences can inform the design of culture media to enable efficient drug screening, isolation of field isolates (including drug resistant strains), and the identification of novel therapeutic targets. This project will provide the student with a broad repertoire of cross-disciplinary skills. 

Supervisors:

 


Development of Generalisable Adaptive Network Models and Application to One Health Disease Problems in Tanzania

Project Description:

Individual behaviour impacts infectious disease spread and control, affecting both how we acquire disease, and how we spread it to others. Adaptive network models, where changes in behavior are represented by changes in how individuals in a population ‘connect’ to others, are a flexible analytical representation of these considerations. Where responses to disease also depend on the adaptive behavior of the others in the network, game theory constructs apply, and this is an approach that has been successfully used in the study of vaccine uptake in human diseases, as is the case for studying MMR vaccine uptake in GB.

The analytical power of adaptive network paradigms is well recognized, but many challenges remain. Two important ones are the acquisition of relevant “qualitative” data on behavior and adaptation, and the consistent interpretation of these qualitative data in quantitative models. Both these challenges require close cooperation across often very different disciplines. In this project, the student will work with established inter-disciplinary teams from the Glasgow-led SEEDZ and SNAP-AMR (which Matthews co-leads) projects, to develop consistent approaches for the integration of qualitative information such as the knowledge of cultural norms and social context, with quantitative information such as economic cost and network structure, to better interpret epidemiological outbreak data.

Building on ongoing modelling analyses in SEEDZ and SNAP-AMR, the student will develop novel network archetypes explicitly considering multi-layer network representations with two types of information transmission across populations, (i) the disease itself, and (ii) knowledge of disease management practice, to explore the implications of adaptive behaviour and the interactions of those two layers. Working with the SEEDZ and SNAP-AMR project teams, the student will establish benchmarks by which to evaluate these models, thereby developing consistent approaches to integrating the data available from these projects, and establishing generalizable paradigms exploitable for understanding other systems.

Supervisors: