About the Project
African swine fever virus (ASFV) causes a highly contagious lethal haemorrhagic fever in domestic pigs that without an effective vaccine is controlled by mass culling of infected and neighbouring herds (doi.org/10.1016/j.tvjl.2017.12.025). A recent ASF disease outbreak in Asia led to the slaughter of millions of domestic pigs (https://www.bbc.co.uk/news/world-asia-48785965). By contrast, in Sub-Saharan Africa where ASFV is endemic, African wild pigs are readily infected, tolerate virus, but do not develop disease. The different responses of wild African and domestic pigs to pathogens reflect their genetic ancestry and will have been shaped by adaptation to their environments, as well as domestication and selection for enhanced productivity. We suggest that studying the interaction between these hosts and ASFV will contribute to a better understanding of the disease, and the development of effective control measures to limit the devastating effects of ASFV.
The cellular host for ASFV is the macrophage, a white blood cell that is normally a first line defence against infections. ASFV infection not only destroys this key mediator of the innate immune response but also causes a “cytokine storm”, similar to other viruses (e.g. SARS-COV-2), that induces uncontrolled inflammation and mass breakdown of the vasculature. We have adapted a novel stem cell-based system (doi.org/10.1038/s41556-019-0333-2), to generate macrophages in culture from both domestic and African wild pigs, and have initiated studies into their differential response to ASFV infection. By comparing the response of the domestic and wild pig macrophages to infection by viruses, we aim to gain key insights into factors affecting host tolerance.
The student will study how domestic and wild African pig macrophages respond to virus infection, and apply state-of-the-art techniques involving the propagation, genetic editing, and differentiation of domestic and wild pig stem cells, transcriptional profiling, and the analysis of virus/host interactions - to functionally investigate the genetic basis of susceptibility and tolerance to ASFV. The Burdon laboratory has a longstanding interest in stem cell biology (doi.org/10.1016/j.stemcr.2019.12.001), most recently applied to livestock species, and has active collaborations with expert virologists and immunologists both at the Roslin Institute and in wider academia and industry.
This project has a strong 3Rs component aimed at reducing the use of animals in research (https://mrcvs.co.uk/en/news-story.php?id=19667).
Training
Laboratory work in this project will involve training in PSC propagation, differentiation and CRISPR/Cas9 gene-editing, gene expression profiling, viral infection of macrophages and a range of immunological assays. The student will learn complementary skills and techniques required for this project in the supervisor’s laboratories. The student will attend weekly research seminars at the Roslin Institute. Opportunities to develop presentation and communication skills will include: regular lab meetings, one-on-one meetings with supervisor(s) on a 1-2 week basis, critical review of research papers at journal clubs, written skills developed in preparation of PhD annual reports, manuscript preparation, and poster and oral presentations at Roslin/CRM internal seminars and UK/international meetings. Additional Courses covering Research and Career Management, Personal Effectiveness and Networking are provided by University of Edinburgh, and offered during the course of research (www.postgrad.ed.ac.uk/pgskills), tailored to students 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).
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