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  EASTBIO: The chicken or the egg; surmounting neonatal immune dysfunction for successful in ovo vaccination


   College of Medicine and Veterinary Medicine

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  Prof L Vervelde, Prof J Hope  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

Royal (Dick) School of Veterinary Studies / The Roslin Institute

In ovo vaccination is an alternative approach to post-hatch vaccination of chickens. It is a safe, animal and user-friendly method that enables vaccination ~60,000 eggs per hour. The technology has been well developed for vaccination against viral diseases using viral vectors and efforts to extend the technology for bacterial and parasitic vaccines are in progress. Although in ovo vaccination can be successful, the immature immune system of a neonate shows functional deficiencies that limit the success rate of this technology.

The in ovo vaccines currently used in the poultry industry are live replicating viruses. To extend and improve this technology for application of inactivated vaccines or adjuvanted subunit vaccines, it is of utmost importance that we understand early life immune ontology and the cellular and molecular mechanisms that affect antigen uptake at mucosal surfaces and induction of immune responses. We will investigate if the avian neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses as previously shown in mammals. Innate immunity also shows functional deficiency in antigen-presenting cells; expression and signalling of Toll-like receptors undergo maturational changes associated with distinct functional responses. Therefore, this project will test the hypothesis that the inherent regulatory constraints of the neonate innate and adaptive immune system can be surmounted by appropriate stimulation. A variety of approaches have been proposed including improved trained innate immunity, altered innate receptor agonists and novel age-specific adjuvantation systems. Gaining a thorough understanding of the immune ontology and cellular and molecular factors that can influence the induction of immune responses in neonates will part of this project.

More recently unique tools to visualise the immune system of the chicken have been developed at The Roslin Institute. In this project, transgenic reporter chickens will be used to visualise antigen presenting cells and specialised epithelial cells, or M cells, to assess their function in antigen uptake and presentation in embryonic chicks [1,2]. Combined with state of the art bio-imaging (https://www.ed.ac.uk/roslin/facilities-resources/bioimaging), the uptake of fluorescent antigens, adjuvants or pathogens can be traced and the immune responses investigated at cellular and molecular level. Throughout this project novel in vivo and in vitro (cell culture systems) models will be used to address the project’s main aims. This studentship will therefore provide excellent training opportunities in state-of-the-art immunology, bioimaging, vaccinology, cell biology and multiplexed PCR platforms [3].

This studentship is a collaborative project with MSD Animal Health and the placement will enable MSD-AH to teach students the essential technical and business skills needed to meet current and future industrial needs.

Eligibility:
All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement.

Funding Notes

Applications:
Completed application form along with your supporting documents should be sent to our PGR student team at [Email Address Removed]

References:
Please send the reference request form to two referees. Completed forms for University of Edinburgh, Royal (Dick) School of Veterinary Studies and the Roslin Institute project should be returned to [Email Address Removed] by the closing date: 5th January 2020.

It is your responsibility to ensure that references are provided by the specified deadline.
Download application and reference forms via:
http://www.eastscotbiodtp.ac.uk/how-apply-0

References

1. Balic A, Chintoan-Uta C, Vohra P, Sutton KM, Cassady-Cain RL, Hu T, Donaldson DS, Stevens MP, Mabbott NA, Hume DA, Sang HM, Vervelde L. 2019 Antigen Sampling CSF1R-Expressing Epithelial Cells Are the Functional Equivalents of Mammalian M Cells in the Avian Follicle-Associated Epithelium. Front. Immunol., doi.org/10.3389/fimmu.2019.02495

2. Sutton K, Costa T, Alber A, Bryson K, Borowska D, Balic A, Kaiser P, Stevens M, Vervelde L. 2018
Visualisation and characterisation of mononuclear phagocytes in the chicken respiratory tract using CSF1R-transgenic chickens. Vet Res., doi: 10.1186/s13567-018-0598-7

3. Borowska D, Kuo R, Bailey RA, Watson KA, Kaiser P, Vervelde L, Stevens MP. 2018 Highly multiplexed quantitative PCR-based platform for evaluation of chicken immune responses. PLoS One. doi: 10.1371/journal.pone.0225658

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