Gene editing for resistance to Foot and Mouth Disease Virus using genome wide CRISPR Cas9 screens
Foot-and-mouth disease (FMD) imposes a significant burden on global agriculture of cattle, pigs, sheep and other livestock. Foot-and-mouth-disease is caused by a picornavirus with 7 distinct serotypes and remains endemic in large parts of the world. Genetic engineering for disease resistance is a potential strategy for preventing FMD in livestock species.
The overall aim of this project is to identify, validate and short list host genes essential for FMDV replication in porcine cells, thereby allowing generation of cells that are resistant to FMDV. This will provide the foundations for the generation of FMDV resistant livestock through precision genome editing.
In recent years technologies such as the CRISPR/Cas9 system have become mainstream approaches for gene editing where specific manipulation of genomes can be readily achieved based on the expression of modified Cas9 protein and simple short guide RNAs. The creation of genome-wide CRISPR libraries consisting of multiple sgRNAs directed at each annotated gene within a genome, has provided a new approach for functional genomics which has become widely established for the identification of host factors required for virus replication in cell lines.
The Grey lab have recently generated one of the first porcine genome-wide CRISPR knockout libraries (https://www.ed.ac.uk/roslin/systems-virology-group). In this project we will use this library to identify porcine genes required for FMDV replication.
In addition to gaining a solid foundation in core molecular virology techniques, the project offers the opportunity to gain experience and expertise in cutting-edge technologies such as CRISPR-Cas9 gene editing, and to contribute towards a solution to this major infectious disease of global importance.
Other projects available:
We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 10th January 2020 at https://www.ed.ac.uk/roslin/work-study/opportunities/studentships
3.5 year PhD
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 project title/s and the supervisor/s in your covering letter.
All applicants should also apply through the University's on-line application system for September 2020 entry via
1 Knight-Jones, T. J. & Rushton, J. The economic impacts of foot and mouth disease - what are they, how big are they and where do they occur? Prev Vet Med 112, 161-173, doi:10.1016/j.prevetmed.2013.07.013 (2013).
2 Newman, J. et al. The Cellular Chaperone Heat Shock Protein 90 Is Required for Foot-and-Mouth Disease Virus Capsid Precursor Processing and Assembly of Capsid Pentamers. J Virol 92, doi:10.1128/JVI.01415-17 (2018).