Vaccine development for important spirochaetal diseases of cattle

Description

*Bovine digital dermatitis (DD) is a severe, infectious, foot skin disease affecting cattle worldwide. This disease causes severe pain resulting in ruminant lameness and impacts animal welfare. Bovine DD results in reduced milk yield and poor reproductive performance costing the UK dairy industry £74 million/year. Existing DD treatments are relatively ineffective. Anaerobic Treponema are considered causal of DD and the University of Liverpool (UoL) currently has substantial experience investigating these microorganisms and is currently working towards development of a vaccine for prevention and control of this important infectious disease.

*Leptospirosis is a worldwide infectious disease affecting a wide range of different host species with notable severity in ruminants and humans. The greatest disease burden for leptospirosis is within tropical/sub-tropical regions where, the causal agents, leptospires can be highly diverse. Bovine leptospirosis (BL) has substantial animal health and welfare costs as well as economic losses estimated at £22.3 million/year in the UK and vastly larger implications for countries with higher disease morbidity. Moreover, BL is a zoonotic threat to man and antimicrobial stewardship issues abound with similar antibiotics used in man and animal. Current vaccines for BL are typically bacterins with limited protection across multiple pathogenic species/serovars that could be causal of disease in tropical regions.

*The development of efficacious, cross-protective vaccines to protect against both bovine DD and leptospirosis would be ideal and likely result in approaches that could be applicable to multiple afflicted host species.

*This proposed studentship would use functional and immunological analyses to pursue identification and characterisation of protein vaccine candidates and seek to engineer targets using artificial intelligence (AI) to enable development of designer vaccines, enabling effective control strategies for these important infectious diseases of cattle.

*This studentship builds on our synergistic programme which uses novel systems approaches linking AI, in silico methods and synthetic biology with immunology to deliver an efficacious vaccine for these severe diseases. The UoL team are in a strong position to deliver this study due to recent uptake of reverse vaccinology approaches and ability to culture fastidious spirochetes. This PhD studentship, based in the Department of Infection Biology and Microbiomes (Leahurst Campus), would collaborate with and basic scientists (with AI and protein structure expertise) from UoL Institute of Systems, Molecular and Integrative Biology and veterinary clinician scientists and pathologists at the University of Liverpool (UoL) Veterinary School to ensure a successful outcome.

*This is a highly interdisciplinary project that sits at the interface between biochemistry, molecular microbiology and vaccinology. You will be primarily based at University of Liverpool Leahurst campus, with some work undertaken at the University of Liverpool main, city centre campus. The student will be able to attend University-run courses in relevant topics and interact with postdoctoral and postgraduate researchers from a range of scientific backgrounds. Substantial training will be provided during the project enabling the student to gain a wide range of core and translational skills that should strategically enable development for a career in a range of different sectors.

Applicants must hold 1st or 2.1 honours degree in a relevant subject, such as Microbiology, Biochemistry, Biological/Biomedical/Bioveterinary/Veterinary Sciences, or a closely related discipline.

For further information, please email Prof. Nicholas Evans: . To apply please forward your covering letter and CV (listing 2 referees) to .

Availability

Open to students worldwide

Funding information

Self-funded project

This studentship would be for a duration of 3-4 years and is open to both European/UK and International students. The studentship is UNFUNDED (self-funded). Prospective applicants are encouraged to contact the listed supervisor directly to discuss their application and the project. If seeking funding from a relevant scheme to support self-funding to undertake this studentship, assistance can be given. The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs of £8000 per year. Details of tuition fees can be found on the University website: 

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Supervisors

References

Staton, G.J., Carter S.D., Ainsworth S., Mullin J., Smith R.F. & Evans N.J., β-barrel outer membrane proteins of the bovine digital dermatitis treponemes: identification and functional characterization. Infect Immun, 2020 Apr 20;88(5):e00050-20.
Staton, G.J., Clegg, S.R., Ainsworth, S., Armstrong, S, Carter, S.D. & Evans, N.J., Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms. PLOS Pathogens, 2021 Mar 29;17(3):e1009464.
Kamaruzaman, I.N.A., Staton, G.J., Ainsworth, S., Carter, S.D. & Evans, N.J., Characterisation of Putative Outer Membrane Proteins from Leptospira borgpetersenii Serovar Hardjo-Bovis Identifies Novel Adhesins and Diversity in Adhesion across Genomospecies Orthologs. Microorganisms, 2024 Jan 24;12(2):245.