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*EASTBIO* A One Health, Genome-wide Approach Investigating the Interplay Between Respiratory Syncytial Virus (RSV) and host defence

  • Full or part time
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

BBSRC Thematic Group: Health
Bovine respiratory syncytial virus (BRSV) affects approximately 1.9 million calves each year in the UK and is considered the most important cause of viral respiratory disease in calves. Similarly, human RSV (HRSV) causes >30% of the global virally-associated respiratory illness in children (see http://perchresults.org/). Together, these enormously successful pathogens place a significant burden on animal welfare and healthcare resources and places substantial pressures on the agroeconomy (ca. £54M/y). BRSV and HRSV are genetically and antigenically very similar and the pathogenesis and epidemiology of infection by these viruses have many features in common. Furthermore, both viruses express analogous proteins (particularly NS1 & NS2) that counteract the host’s innate immune response showing that, despite their strict host range, they are highly related. What host factors are key to the success of these viruses is largely unknown; likewise, knowledge of how the host defence system attempts to limit their replication is also lacking. Importantly, there are no licenced vaccines and current therapeutic interventions are limited. Therefore, a detailed comparative analysis will significantly improve our understanding these exquisitely successful pathogens that could translate in to the development of new therapeutics.

Project overview:
Based on the ‘One Health’ principle, this project provides a comparative examination of the host factors required for RSV replication and the critical antiviral factors responsible for limiting infection. Drawing on expertise in viral diseases in cattle (Dr Dalziel) and humans (Dr Hughes), this project will take advantage of the newly established bovine, genome-wide CRISPR/Cas9 loss-of-function screen (developed in Dr Dalziel’s laboratory) to investigate BRSV. Concurrently, a human genome-wide CRISPR/Cas9 screen will be performed to investigate HRSV. Knock-out cells unable to support RSV infection will survive; these will be expanded, and the critical factors required for replication will be identified using next generation sequencing (NGS) and validated using various state-of-the-art virological and biochemical techniques. To investigate which host defence factors are important for limiting infection, a similar screen will involve pre-treating cells with species-specific interferon, to mimic a pre-existing antiviral state, and then infected using reporter viruses that express fluorescent proteins. Cells in which a critical antiviral factor has been knocked out will support RSV replication; these cells will be isolated by fluorescence-activated cell sorting (FACS), and the essential antiviral gene will be identified using next generation sequencing followed by thorough validation. Detailed comparisons will be made to identify both shared and unique pathways used by each virus.

This highly focussed project, which has implications for our fundamental understanding of host defence, health and disease, is designed to provide training in cutting-edge genomics and molecular virology methods that will equip the PhD student with the skills required to be competitive in their future scientific endeavours.

The successful candidate will receive training in a wide variety of state-of-the-art techniques. You will join a supportive and friendly collaborative team studying viruses relevant to human and animal health in purpose-built and well-equipped laboratories.

Funding Notes

This project is eligible for the EASTBIO Doctoral Training Partnership: View Website

This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body.

Apply by 5.00 pm on 5 January 2020 following the instructions on how to apply at: View Website

Please also upload the EASTBO Application Form as an additional document to the University of St Andrews online Application.

Informal inquiries to the primary supervisor are very strongly encouraged.

How good is research at University of St Andrews in Biological Sciences?

FTE Category A staff submitted: 50.45

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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