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EASTBIO: The chicken or the egg; unravelling immunological mechanisms of 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 (Students Worldwide)

About the Project

We have an exciting opportunity for an enthusiastic Ph.D. student with an appropriate immunology, cell biology or veterinary degree to study neonatal immune immunological pathways that lead to succesful in ovo vaccination.
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.

Funding information and application procedures:
This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP) http://www.eastscotbiodtp.ac.uk/how-apply-0 .

EASTBIO Application and Reference Forms can be downloaded via http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO Application Form along with a copy of your academic transcripts to [Email Address Removed]

You should also ensure that two references have been send to [Email Address Removed] by the deadline using the EASTBIO Reference Form.


Funding Notes

This opportunity is open to UK and international students and provides funding covering stipend and UK level tuition fees. The University of Edinburgh covers the difference between home and international fees meaning that the EASTBIO DTP offers fully-funded studentships to all appointees. There is a cap on the number of international students the DTP recruits. It is important that we know from the outset which fees status category applicants fall under when applying to our university.

Please refer to UKRI (https://www.ukri.org/our-work/develop ing-people-and-skills/find-studentships-and-doctoral-training/get-a-studentship-to-fund-your-doctorate/) and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria (https://www.ukri.org/wp-content/uploads/2020/10/UKRI-291020-guidance-to-training-grant-terms-and-conditions.pdf).


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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