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Host-pathogen interaction studies of hepatitis E virus

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  • Full or part time
    Dr C Burkard
    Prof J Haas
    Dr T Opriessnig
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Hepatitis E virus (HEV) infection in adults can result in acute hepatitis and chronic hepatitis in immunocompromised patients. In developing countries tansmission of the virus mainly occurs via contaminated water and food by the fecal oral route, with genotypes 1 and 2 being the primary cause of infection. In industrialized countries zoonotic transmission of HEV is prevalent with porcine zoonosis being the major source of transmission in Europe, associated with genotypes 3 and 4. Infections in the pig are usually asymptomatic but seroprevalence is high, reaching 80-100% in the UK.
Between 2004 and 2016 notified, laboratory-confirmed cases of HEV increased 15-fold in Scotland, reflecting a national trend (1). Most of these cases were caused by genotype 3 viruses, highlighting the importance of zoonotic transmission.
Unpublished results from the lab of J. Haas show that genetic variations in the cellular immune response are linked to disease severity in hospitalised patients. This highlights an urgent need to better understand the host-pathogen interaction of HEV in both humans and pigs to prevent disease spread and devise new antiviral treatment stategies. One of the major hindrances in understanding HEV is the lack of suitable cell culture systems to cultivate field isolate viruses, however, recent advances show that stem cell-derived hepatic cells and organoids (SCDCs) may be used for virus isolation and cultivation (2).
Within this project the student will investigate three objectives: 1) to develop new stem cell-derived culturing systems to grow field-isolate HEVs, 2) to perform an siRNA screen using hepatic human cell lines and culture-adapted virus to identify host genes involved in HEV infection, and 3) to investigate the role of genetic variation in cellular immune genes and follow up on host genes involved in HEV infection in SCDCs and cell line cultures.
This 3.5-year studentship will provide excellent training in a variety of fields of biology, including cell biology, virology, biochemistry and molecular biology. The successful candidate will learn and apply a wide variety of techniques and transferable skills.

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

Funding Notes

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
http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=831

References

(1) Thom K, Gilhooly P, McGowan K, et al. Hepatitis E virus (HEV) in Scotland: evidence of recent increase in viral circulation in humans. Euro Surveill. 2018;23(12):17-00174. doi:10.2807/1560-7917.ES.2018.23.12.17-0017
(2) Himmelsbach K, Bender D, Hildt E. Life cycle and morphogenesis of the hepatitis E virus. Emerg Microbes Infect. 2018;7(1):196. Published 2018 Nov 29. doi:10.1038/s41426-018-0198-7

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