The South West Biosciences Doctoral Training Partnership PhD is a fully-funded, four-year programme designed to provide training in cutting edge world-class bioscience and food security research skills. Linking these two research themes is a thorough training in numerical and systems based approaches. The DTP projects, funded by the BBSRC, are designed to provide outstanding interdisciplinary training in a range of topics in Food Security and World-Class Bioscience, underpinned by training in mathematical approaches.

The SWBIO follows a 4-year PhD model. In the first year, students receive a range of directed training tailored to support their PhD project. This includes a series of compulsory taught units and self-directed study that take up about one-third of the students’ available time. In addition students will experience two assessed laboratory rotations in year 1, each in separate disciplines but designed to provide focused training tailored for their PhD project. 

Students will also continue their skills development training throughout their PhD via the PIPS (Professional Internships for Postgraduate Studies) scheme, an annual Research Conference, workshops and online skills training provision.

A single studentship is available for each project described below.


Prevention of Keel Bones breakage in Laying Hens - Defining a Fracture Resistant Phenotype through Computer Modelling

Main supervisor: Dr John Tarlton, (School of Veterinary Science, University of Bristol)
Second supervisor: Prof Kate Robson-Brown (Department of Archaeology and Anthropology University of Bristol)
Other supervisors: Prof Richie Gill (University of Bath), and Prof Krasimira Tsaneva-Atanasova (University of Exeter)

This is a very exciting project addressing the most important and urgent problem of farm animal welfare, by applying state of the art technology in imaging, engineering, biochemistry, and computer modelling.

Bone fracture is a significant health problem in most vertebrates, causing pain, impaired function, and even fatality. In particular, bone breakage in laying hens is a serious health, welfare and economic issue, with an estimated 138 million hens suffering keel bone fractures in the EU. How bones respond to mechanical loading is fundamental to understanding fractures. Finite-element analysis (FEA) is a method of mathematical modelling used in engineering to explore interactions between geometry, mechanical properties and loading. FEA has recently been used to estimate the mechanics of biological tissues such as bone, using non-destructive micro-computed tomography (μCT). However, such techniques have not fully accounted for detailed variations in bone composition, nor have they been validated against actual small scale mechanical properties. This study will combine μCT/FEA with analysis of detailed molecular composition and multi-scale biomechanics to mathematically model avian keel bones, both intact and with previous fractures, using (non-)linear elastic fracture mechanics. Topographical analysis will then be used to construct virtual keels to model in-silico the effects of different impacts, changes in shape, composition and previous fractures. This study will synergise with a large current BBSRC funded project mathematically modelling actual fractures in keel bones by ex-vivo impact analysis in real housing conditions using tri-axial accelerometry.

The student will benefit from training by world leading experts in biomechanics, engineering, computed tomography, bone biology, FEA and mathematical modelling, and will develop computational models with a wide range of applications in different bones and across species. The multidisciplinarity of this project opens up diverse career opportunities in both academia and commercial science. The project would suit an engineer wishing to apply engineering principles to bone biology, a welfare scientist wishing to apply cutting edge technology in order to benefit animal welfare, or a biologist with a desire to understand the fundamental functionality of bone.

Two First Year Mini Projects are proposed:

1. Relationship between age related compositional changes in bone and susceptibility to fatigue fractures. (Tarlton).
2. Mapping the response to micro-indentation loading of keel bones, and applying finite element modelling to relate this to detailed micro-structural and compositional differences. (Robson-Brown).

Closing date Jan 9th. Applicants are encouraged to contact supervisors (john.tarlton<στο>bristol.ac.uk,kate.robson-brown<στο>bristol.ac.uk, R.Gill<στο>bath.ac.uk or K.Tsaneva-Atanasova<στο>exeter.ac.uk).

Dr John Tarlton (http://www.bristol.ac.uk/vetscience/people/john-f-tarlton/index.html)

Prof Kate Robson-Brown (http://www.bristol.ac.uk/school-of-arts/people/katharine-a-robson-brown/index.html). Prof Richie Gill (http://www.bath.ac.uk/mech-eng/people/gill/index.html)

Prof Krasimira Tsaneva-Atanasova (http://emps.exeter.ac.uk/mathematics/staff/kt298)

For more information on this project and to apply, visit:

http://www.bris.ac.uk/swdtp/projects_available/2015_projects_available/2015_fs_bristol.html


Big Data Approaches to Livestock Health and Welfare at the One Health-Food Security Interface

Main supervisor: Prof. Mark Eisler (School of Veterinary Science, University of Bristol)
Second supervisor: Dr Katy Turner (School of Veterinary Science, University of Bristol)

The project will investigate relationships among human and animal health, welfare and demographics, consumption of animal products, land use, and geopolitical and socioeconomic predictor variables, thereby enhancing understanding of the role of farmed livestock in global food security. The project will exploit a number of public access online databases including (i) FAOSTAT a large database relating to hunger, food and agriculture, (ii) World Bank Open Data, free and open access to country-level development data, (iii) the World Animal Health Organisation’s (OIE) new World Animal Health Information System (iv) the ProMED-mail reporting system for rapid global dissemination of information on outbreaks of infectious diseases and acute exposures to toxins that affect human animal and plant health and (v) the Infectious Diseases (EID2) evidence-based database on vectors, hosts and their pathogens including spatial and temporal distributions and potentially climate-sensitive data. Data mining and modelling approaches will be used to investigate livestock numbers, consumption of meat and other animal products, and transboundary and zoonotic disease reporting at individual country level. The project will focus particularly on counties with partner research institutes in the Global Farm Platform initiative.

Multivariate analysis methods such as principal components and factor analysis will be used to reduced dimensionality of variables to be used in generalised and linear mixed-effect regression modelling. Model outputs will be incorporated into geographical information systems, representing animal production, health and welfare, zoonotic disease risk and ecosystem service and biodiversity impacts for various future scenarios representing intensification or extensification of livestock production. Ground-truthing of model predictions will be conducted in collaboration with Global Farm Platform partners.

For more information on this project and to apply, visit:

http://www.bris.ac.uk/swdtp/projects_available/2015_projects_available/2015_fs_bristol.html


Structural and functional basis of effective immunity against Theileria parva infection in cattle

Main supervisor: Prof. Linda Wooldridge (School of Veterinary Sciences, University of Bristol)
Second supervisor: Dr Paul Race (School of Biochemistry, University of Bristol)
Other supervisors: Dr Timothy Connelley (Roslin Institute, University of Edinburgh), Dr Hugo van den Berg (Systems Biology Centre, University of Warwick)

Theileria parva is a protozoan parasite of cattle which causes an acute and usually fatal lymphoproliferative disease known as East Coast Fever (ECF). ECF is a major constraint on cattle production in a large area of sub-Saharan Africa, causing estimated losses of USD300 million/year. CD8 T-cells have been shown to provide immunity against T. parva infection and therefore, the development of vaccines that stimulate CD8 T-cell immunity hold great promise for disease control. Immunisation with a single T. parva strain provides effective long lasting immunity against the homologous strain. However, protective immunity against heterologous strains is extremely variable which represents a major barrier to the development of an effective vaccine program. The objective of this PhD is to examine the structural and functional basis of strain-specific immunity against T. parva, which will inform rational design of effective vaccines for ECF control. The successful candidate will apply structural analysis of TCR/pMHCI interactions and systems biology approaches to sets of well characterized CD8 T-cell clones specific for naturally occurring T. parva epitope variants to investigate the structural and functional basis of cross-reactivity. To achieve this, the student will receive training in functional analysis of T-cells, protein biochemistry and mathematical analysis of T-cell crossreactivity. The project is a collaboration between the School of Veterinary Sciences, University of Bristol, The Roslin Institute, University of Edinburgh and The Systems Biology Centre, Warwick University.

For more information on this project and to apply, visit:

http://www.bris.ac.uk/swdtp/projects_available/2015_projects_available/2015_fs_bristol.html


Effects of contrasting grassland systems on phosphorus cycling: forms and quantities of phosphorus in animal wastes and impact on transfers to surface waters.

Main supervisor: Dr Michael Lee (School of Veterinary Sciences, University of Bristol)
Second supervisor: Dr Martin Blackwell (North Wyke, Rothamsted Research)
Other supervisors: Dr Mark van der Giezen (College of Life and Environmental Sciences, University of Exeter)

This project will investigate the effects of livestock diet on phosphorus in animal waste in order to understand the implications for its transfer to land and surface waters.

Agricultural phosphorus management is an important factor in the drive towards Food Security largely due to the fact that phosphorus resources are finite. In addition, its presence in surface waters currently is the most common cause of water quality failure of freshwater bodies under the EU Water Framework Directive in England.

The major objective of this study is that farms can be better managed to minimise losses, improve phosphorus use efficiency, and balance trade-offs between production and environmental impacts. Agriculture has been implicated as one of the major contributors of phosphorous release into the environment and therefore a concern regarding sustainable intensification. Changes in animal diet are known to alter rumen microbial populations which have been shown to be a factor in phosphorus utilisation in ruminant animals. This subsequently impacts the forms, availability and susceptibility of phosphorous transfer to surface waters via animal wastes. It is vital that the cycling, dynamics and quality of phosphorus in agricultural systems are better understood at all stages of the food production cycle, especially in the field and the animal. Using the Rothamsted North Wyke Farm Platform (NWFP) we will develop a model for phosphorus cycling across the three treatment farmlets to better understand the impact of diet on phosphorus within the animal and the environment. No studies have previously sought to understand the combined effects of these factors on phosphorus cycling and transfer at a whole farm-scale.

The student will receive world-class training in three main areas. Firstly, in sampling and analysis (soil/water/vegetation/faecal deposits/fertilisers) for determination of phosphorus forms and quantities using cutting edge techniques including 31P-NMR, HPLC, enzyme hydrolysis and δ18O-PO4 tracing techniques. This will be provided in the laboratories at North Wyke. Secondly, sampling and analysis of rumen digesta and blood plasma will be taught in the veterinary laboratories at the University of Bristol. Finally, techniques in microbial diversity of rumen digesta using NGS will be taught at the University of Exeter. The laboratories at North Wyke and Bristol will comprise the first year project rotations, with time also spent at the University of Exeter, which is a 30-minute drive from North Wyke, during the course of the PhD. Training will combine modern techniques in animal, microbial and environmental science, providing the student with a strong suite of skills enhancing future employment options.

This proposal provides a novel perspective on how grassland systems, animal diet and processing of phosphorus effect not only the wider environment but are tantamount in securing sustainable food production for future generations.

The closing date for applications is 15th Jan 2015. Interested candidates are strongly advised to contact the project supervisors: Dr. Michael Lee (michaelrf.lee<στο>bristol.ac.uk), Dr. Martin Blackwell (martin.blackwell<στο>rothamsted.ac.uk), or Dr. Mark van der Giezen (m.vandergiezen<στο>exeter.ac.uk) as soon as possible.

For more information on this project and to apply, visit:

http://www.bris.ac.uk/swdtp/projects_available/2015_projects_available/2015_fs_bristol.html


Emotion and decision-making: disentangling underlying processes

Main supervisor: Professor Mike Mendl (School of Veterinary Science, University of Bristol)
Second supervisor: Professor Iain Gilchrist (School of Psychology, University of Bristol)
Other supervisors: Professor Peter Dayan (Gatsby Computational Neuroscience Unit, UCL), Dr Liz Paul (School of Veterinary Science, University of Bristol)

Humans in negative emotional (affective) states are more likely to make negative judgements about ambiguous stimuli (e.g. words, facial expressions) than happier people – so-called judgement biases. Findings from over 45 studies using a translational task developed in our lab (Harding et al. 2004. Nature427, 312) indicate that the same relationship between affect and decision-making under ambiguity also exists in a range of non-human animals. Judgement biases may thus be valuable new indicators of animal affect and welfare. However, the psychological processes underlying these findings remain unknown. Affective states might alter subjective probabilities and/or valuations of decision-outcomes, and may influence sensory perceptual processes such as stimulus generalization. Disentangling these processes will offer important new insights into the links between affect and decision-making.

The aim of this PhD is to investigate the processes by which affective states alter decisions, and the extent to which these show parallels across humans and rodents. Carefully controlled experiments, e.g. sensory discrimination paradigms that are designed and interpreted via quantitative computational and mathematical models, will be employed. Combining modelling and experiments has proved a very fruitful enterprise in decision-making research, and we will exploit these close links. The student will receive training in animal learning and behaviour, perceptual and affective psychology, and computational theory and modelling from a supervisory team with expertise in all areas. They will learn to design perceptual discrimination tasks, to programme and use automated operant equipment, and to implement computational, statistical and trial-by-trial analysis of complex datasets.

For more information on this project and to apply, visit:

http://www.bris.ac.uk/swdtp/projects_available/2015_projects_available/2015_wcb_bristol.html


Spatial management of livestock grazing for sustainable parasite control

Main supervisor: Dr Eric Morgan (School of Veterinary Science, University of Bristol)
Second supervisor: Dr Colin Torney (Department of Mathematics, University of Exeter)
Other supervisors: Dr Christos Ioannou (School of Biological Sciences, University of Bristol)

Parasitic diseases cause major negative impacts on the health, welfare and productivity of grazing livestock. Their control is essential to sustainable intensification in support of food security, but is threatened by the emergence of anthelmintic drug resistance (AR) [1]. Although mathematical modelling has been used to inform general strategies for the development of AR [e.g. 2], these make simplifying assumptions on farm management, which are at odds with the recent emphasis on targeting treatment within flocks and herds [3]. Crucially, the effectiveness of refugia for susceptible genotypes, generated by targeted treatment and a lynch-pin of sustainable parasite control [4], will depend strongly on their spatial distribution. Currently, no model frameworks exist to explore the spatial interactions between anti-parasite treatments, livestock movement, climatic factors, and the development of AR. This is an important deficit, both in terms of providing specific guidance to farmers on practical control strategies, and for predicting the effect of future climate and land use change on their effectiveness.

This project would build, validate and apply spatial models of parasite transmission in grazing livestock systems, to predict the development of AR across a range of treatment, climate and livestock movement scenarios. Outcomes will be improved understanding of the spatial processes leading to AR and how they can be influenced by farm management, and practical recommendations to enable farmers to exploit these processes to enhance the sustainability of production.

Mini-project 1 (Bristol, Morgan) will train the student in parasitological laboratory methods, including up to date methods for the in vitro detection of anthelmintic resistance. This will provide them with the skills base to validate models in the field by cross-sectional and longitudinal studies that measure AR development on farms. A small survey of AR on cattle and sheep farms will provide baseline data and build a network for the main PhD study. This project will be based in Bristol to facilitate attendance of taught components.

Mini-project 2 (Exeter, Torney) will provide training in the modelling of animal movement, considering how interactions within a herd or flock impact on group cohesion and collective movement, and how this then affects interactions with the environment, including parasite transmission patterns. The student will learn spatial modelling techniques that will be carried forward to the main project.

References: [1] Kaplan and Vidyashankar Veterinary Parasitology 2012:4:186:70-78; [2] Barnes, Dobson and Barger Parasitology Today 1995:11:56-63; [3] Charlier, Morgan et al. Veterinary Record 2014;175:250-255; [4] Van Wyk Onderstepoort Journal of Veterinary research 2001:68:55-67.

For more information on this project and to apply, visit:

http://www.bris.ac.uk/swdtp/projects_available/2015_projects_available/2015_fs_bristol.html


Viral-bacterial interactions in the upper respiratory tract of pigs

Main supervisor: Prof. Mick Bailey (School of Clinical Veterinary Sciences, University of Bristol)
Second supervisor: Professor Adam Finn (Schools of Clinical Sciences and Cellular and Molecular Medicine, University of Bristol)

Intervention studies in laboratory rodents and in agricultural species have demonstrated that colonisation with commensal microbiota contributes to development of the mucosal and systemic immune systems, particularly in neonates. In human infants, epidemiological studies also implicate the microbiota in protection or predisposition to several diseases involving immune dysfunction, including allergies and autoimmune diseases. However, expression of immune responses at mucosal surfaces can also affect the composition of the microbiota. Thus, the interaction between mucosal immune system and the microbiota seems to be bi-directional and, unsurprisingly, complex.

Mick Bailey’s laboratory has demonstrated that a range of environmental factors influence both the development of the microbiota and the potential for immune responses to defined antigens in piglets. By extension, it seems likely that some of the inter-individual variation in response to vaccination in farm animals is determined by the pattern of mucosal colonisation with microbiota. Further, it seems likely that manipulation of this microbiota in agricultural species may contribute to maximising the effectiveness of vaccination.

Adam Finn’s laboratory has recently demonstrated that mucosal immunisation of human infants with attenuated influenza virus can modulate carriage and shedding of a series of bacteria which fall into the class of ‘normal commensals but occasional pathogens’ (e.g. Haemophilus influenzae, Strep. pneumoniae, Moraxella catarrhalis, Staph. aureus). The clinical significance of these observations is not clear, but they clearly imply that vaccination is likely to modulate onward transmission of a range of antigenically unrelated potential pathogens.

Under a current BBSRC award (sLoLa BB1001330/1) we have extensive funding for a series of vaccination and infection experiments in pigs using, specifically, strains of the H1N1 2009 pandemic influenza (‘swine flu’, which has now re-crossed back into pigs to become the dominant strain). These include: time course of infection with virulent influenza virus using serial post-mortem allowing full tissue sampling; vaccination efficacy using at least 8 different formulations plus controls, and finishing with a full challenge with virulent virus; transmission studies in which infected pigs are exposed to a series of vaccinated or unvaccinated pigs for short periods (24 hours) to assess onward transmission through several cycles. Current expertise includes virology and immunology but we had not planned sampling to determine either the effect of respiratory microbiota on response to vaccination or infection or vice-versa. The transmission experiments proposed will also allow us to examine co-transmission of commensals/opportunist pathogens (such asStrep. suis, Haemophilus parasuis, Mycoplasma hyorrhinis) along with influenza virus.

For more information on this project and to apply, visit:

http://www.bris.ac.uk/swdtp/projects_available/2015_projects_available/2015_fs_bristol.html


Establishing a reverse genetic system for field-derived feline coronaviruses – a step towards effective feline infectious peritonitis vaccination

Main supervisors: Dr Andrew Davidson (School of Cellular and Molecular Medicine, University of Bristol) and Dr Séverine Tasker (School of Veterinary Sciences, University of Bristol).
Other supervisors: Professor Linda Wooldridge (School of Veterinary Sciences, University of Bristol)

Feline infectious peritonitis (FIP) is a fatal disease in young cats arising from (type 1) feline coronavirus (FCoV) infection. There is an urgent need to develop an effective FCoV vaccine that protects against this disease, which is distressing for cats, their owners and the veterinary surgeons dealing with them. The type 1 FCoV cell entry receptor (CER) is currently unknown, which has impeded the propagation of field-derived FCoVs in vitro. This has prevented the production of recombinant attenuated FCoVs, which are essential for FCoV vaccine development.

With recent technical advances, we can now circumvent these barriers. The first aim of the project is to use a novel high-throughput proteomic approach to identify the FCoV CER, which will facilitate the generation of feline cell lines that allow field-derived FCoV propagation. We have recently sequenced the genomes of multiple field-derived FCoVs. The second aim of the project is to use this sequence information, in combination with the identified CER, to establish a reverse genetic system for a representative FCoV, using a rapid synthetic biology approach. This will be a powerful technological platform for vaccine development. Accordingly, in the third aim of the project, the FCoV genome will be genetically manipulated to produce novel attenuated recombinant viruses that can serve as candidate vaccine strains, which would be a major step forward in preventing FIP.

The student will work within a multi-disciplinary team engaged in coronavirus and feline infectious disease research. The project will use the University of Bristol’s state-of-the-art proteomic and synthetic biology facilities and the student will receive training in high- throughput proteomics and advanced bioinformatics. Training will also be provided in immunology, cell culture, advanced molecular cloning techniques and statistical analysis. The project will also include a three month placement at BioBest laboratories, Edinburgh, UK a leading international specialist veterinary laboratory.

For more information on this project and to apply, visit:

http://www.bris.ac.uk/swdtp/projects_available/2015_projects_available/2015_wcb_bristol.html