Resistance of warthogs to African Swine Fever Virus

Background: African swine fever (ASF) is a severe infectious disease of domestic pigs and wild boar caused by African swine fever virus (ASFV). Although ASFV replicates to high titres in experimentally infected warthogs and bushpigs the animals remain asymptomatic. Thus, resistance in these Suidae species concerns progression to disease rather than initial host-virus interactions, viral entry or replication. This project will identify and investigate potential mechanisms that enable warthogs and bushpigs to tolerate high ASFV loads and resist the terminal haemorrhagic cascade of ASF disease.

Hypothesis: Differences in the pig and warthog genomes underpin the relative resistance of warthogs to ASFV

Approach: The student will compare the pig (Sus scrofa) and warthog (Phacochoerus africanus) genomes at Roslin (months 1-12). Sequence variants will be identified and prioritised for further study using evolutionary approaches and by characterising their potential functional impact on proteins and gene regulation. Sequence data are already available, including the pig reference genome sequence (Sscrofa11.1), and draft genome sequences for warthog, Red River Hog (Potamochoerus porcus) and bushpig (Potamochoerus larvatus) which are similarly susceptible to infection with ASFV but asymptomatic.
The student will undertake experiments to examine the role of identified genes in conferring resistance to ASF at The Pirbright Institute (months 13-48), e.g.
• Modification of host genes in Vero cells using CRISPR/Cas9 technology then use of the Vero cell-adapted BA71V strain of ASFV
• Over-expression and comparison of the function of warthog or domestic pig genes in appropriate in vitro models such as reconstitution of the suidae DNA sensing pathway in HEK293 cells
• Over-expression and purification of recombinant pig and warthog proteins for use in protein-protein interaction studies such as pull-down assays or surface plasmon resonance
• Modification of target genes or pathways in primary pig macrophages prior to virulent ASFV infection by pharmacological manipulation [2] or lentivirus transduction [3].

Application procedures
Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed].

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

All applicants should also apply through the University’s on-line application system for September 2018 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=830

Applicants for the Principal’s career development studentship must also complete the specific on-line application form.

Applicants for an Enlightenment Scholarship must also complete the specific on-line application form.
ALL APPLICATION PROCEDURES MUST BE COMPLETED BY THE CLOSING DATE 16th January 2018