Transmission of infectious disease between wild and domestic species is a major concern for agriculture, wild life management, and human health - as demonstrated by recent global pandemics. The overall aim of this project is to generate appropriate host cell types from disease resilient and susceptible animals using stem cell technologies, to study and compare host-pathogen interactions in different species. An advantage of the stem cell-based platform is that it can deliver an unlimited supply of differentiated cells without requiring repeated sampling from animals (of course impractical and unethical in wild animals), and is readily amenable to CRISPR/Cas9 gene editing techniques. This approach provides new opportunities to investigate how host genetics and molecular biology influence disease in the biologically appropriate genetic backgrounds (Meek et al., 2021)1.
Our experimental system is founded on the different responses of domestic and wild African pigs to African swine fever virus (ASFV). In wild African pigs ASFV is endemic and causes no discernible disease. By contrast, in domestic pigs ASFV infection causes a lethal haemorrhagic fever that results in death within 7-10 days. In the absence of commercially available vaccines, attempts to curb the spread of ASFV in a recent ASF disease outbreak in eastern Europe and Asia resulted in the slaughter of millions of domestic pigs (https://www.bbc.co.uk/news/world-asia-48785965). ASFV therefore represents a serious and ongoing threat to global food security and animal welfare.
The macrophage is the primary cellular host for ASFV. Deregulation and destruction of this key mediator of innate immunity by ASFV infection leads to a “cytokine storm” that causes uncontrolled inflammation and breakdown of vasculature. We have developed a stem cell-based system that produces macrophages in culture from both domestic and African wild pigs, and have initiated studies into their differing responses to ASFV. The student will study host tolerance by comparing the response of the domestic and wild pig macrophages to infection by viruses. The project will entail analysis of transcriptional data sets, propagation and gene editing stem cells, and functional analysis of responses to ASFV in domestic and wild pig macrophages.
This project aligns closely with the 3Rs ethos - reducing, refining and replacing animals in research (https://mrcvs.co.uk/en/news-story.php?id=19667).
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to Tom Burdon ([Email Address Removed]).