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A single cell approach to analysing the bovine ultralong antibody response to African trypanosomes

  • Full or part time
    Dr L Morrison
  • Application Deadline
    Sunday, April 21, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Cattle uniquely express a proportion of their antibodies with an elongated antigen-binding domain, which are thought to bind to epitopes inaccessible to conventional antibodies[1]. Trypanosomes, vector-borne protozoa that cause serious human and animal disease across sub-Saharan Africa, cloak their surface with a variable protein, which creates a physical barrier preventing conventional antibodies binding to underlying invariant epitopes[2]. However, bovine ultra-long antibodies can perhaps bind such epitopes, raising the possibility of targeting the bovine immune response to trypanosome proteins. The supervisory team have generated an experimental and analytical pipeline that enables isolation and analysis of antigen-specific single bovine B cells.

The student will build upon this foundation in order to characterise in depth the bovine B cell response to immunisation. This will employ novel single cell approaches to isolating single antigen-reactive B cells from cattle immunised with selected proteins, and characterising both the nature and dynamic of the B cell response as well as the expressed immunoglobulin heavy and light chain sequences, including those with ultralong CDR3 domains. Selected immunoglobulins will be generated as recombinant antibodies, and tested for binding against target antigens. Such results would significantly improve our knowledge of the bovine adaptive immune response, and inform on the potential utility of bovine ultra-long antibodies in vaccinology.

The student will greatly benefit from the existing partnership and complementary skills of the experienced supervisory team who collaborate across two world-class research institutes; Roslin and Pirbright are leading the development of these methodologies in veterinary species. The approaches have broad relevance to efforts aimed at dissecting the fine specificities of antibody responses in animal species. The successful candidate will be trained in immunology-focused laboratory skills (flow cytometry/FACS, cell culture, immunohistochemistry) and bioinformatics (single cell transcriptome analysis), resulting in cross-disciplinary abilities that will provide a highly competitive platform for a career in science.

Funding Notes

Funding: This project is eligible for a University of Edinburgh 3.5 year PhD studentship.

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.

Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to

When applying please state clearly the title of the studentship and the supervisor/s in your covering letter.



References

Wang F, Ekiert DC, Ahmad I, Yu W, Zhang Y, Bazirgan O, et al. Reshaping antibody diversity. Cell. 2013;153(6):1379-93.
Matthews KR, McCulloch R, Morrison LJ. The within-host dynamics of African trypanosome infections. Philos Trans R Soc Lond B Biol Sci. 2015;370(1675).

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