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Harnessing Cell-Mediated Immunity to Cytomegalovirus for Personalized Antiviral Therapy


Project Description

Human cytomegalovirus (CMV) establishes lifelong latent infections in most of us. Although CMV does not usually cause severe disease in healthy people, the virus is a leading cause of birth defects and a major pathogen in individuals with weakened immune systems including transplant patients. There is no vaccine for CMV, and antiviral treatment is costly and comes with serious side effects. To inform decision-making for antiviral therapy after transplantation, novel immune-based diagnostic assays are being developed. The immediate-early 1 (IE1) and pp65 proteins, two highly immunogenic CMV antigens, are integral components of many candidate vaccines and diagnostic assays including T-Track® CMV developed by Lophius Biosciences. IE1 and pp65 also make key contributions to CMV biology, including innate immune evasion, in ways that remain to be fully explored.

The successful candidate will examine in human cells how the two viral proteins impact CMV replication and reactivation from latency by targeting critical pathogen sensing and signalling mechanisms. He/she will also optimize IE1 and pp65 protein production and engineer mutant proteins with improved activities in the T-Track® CMV assay. The student will work as part of a CMV research team at the University of St Andrews, using cutting-edge molecular biology and virology techniques. The work will be conducted in collaboration with Lophius Biosciences and will involve regular visits to the company’s premises in Germany.

This interdisciplinary project at a crossroads between biology and medicine will offer a unique opportunity to explore both academic and corporate research settings. The outcomes will help improve and personalize the management of CMV infection in immune-suppressed patients, inform vaccine development, and elucidate virus-host interactions underlying CMV disease.

For further information please contact Dr Michael M Nevels (principal supervisor, ) or Dr Simon J Powis (second supervisor, ).

Funding Notes

Excellent candidates from the UK or EU (outside UK) are encouraged to apply by submitting the usual documents including their CV and a covering letter. Outstanding candidates from overseas will also be considered. Applicants must have obtained, or be about to obtain, a first or upper second class Honours degree, Masters degree or equivalent in a relevant subject. The studentship is generously funded by Medical Research Scotland for 4 years and includes a stipend above national UKRI standard rate and UK/EU tuition fees as well as travel allowances. International fees are not covered.

References

Wu CC, Jiang X, Wang XZ, Liu XJ, Li XJ, Yang B, Ye HQ, Harwardt T, Jiang M, Xia HM, Wang W, Britt WJ, Paulus C, Nevels M, Luo MH. 2018. Human cytomegalovirus immediate early 1 protein causes loss of SOX2 from neural progenitor cells by trapping unphosphorylated STAT3 in the nucleus. J Virol. 92(17):e00340.
Banas B, Steubl D, Renders L, Chittka D, Banas MC, Wekerle T, Koch M, Witzke O, Mühlfeld A, Sommerer C, Habicht A, Hugo C, Hünig T, Lindemann M, Schmidt T, Rascle A, Barabas S, Deml L, Wagner R, Krämer BK, Krüger B. 2018. Clinical validation of a novel ELISpot-based in vitro diagnostic assay to monitor CMV-specific cell-mediated immunity in kidney transplant recipients: a multicenter, longitudinal, prospective, observational study. Transpl Int. 31:436.
Liu XJ, Yang B, Huang SN, Wu CC, Li XJ, Cheng S, Jiang X, Hu F, Ming YZ, Nevels M, Britt WJ, Rayner S, Tang Q, Zeng WB, Zhao F, Luo MH. 2017. Human cytomegalovirus IE1 downregulates Hes1 in neural progenitor cells as a potential E3 ubiquitin ligase. PLoS Pathog. 13(7):e1006542.
Banas B, Böger CA, Lückhoff G, Krüger B, Barabas S, Batzilla J, Schemmerer M, Köstler J, Bendfeldt H, Rascle A, Wagner R, Deml L, Leicht J, Krämer BK. 2017. Validation of T-Track® CMV to assess the functionality of cytomegalovirus-reactive cell-mediated immunity in hemodialysis patients. BMC Immunol. 18:15.
Barabas S, Spindler T, Kiener R, Tonar C, Lugner T, Batzilla J, Bendfeldt H, Rascle A, Asbach B, Wagner R, Deml L. 2017. An optimized IFN-γ ELISpot assay for the sensitive and standardized monitoring of CMV protein-reactive effector cells of cell-mediated immunity. BMC Immunol. 18:14.
Reuschel E, Barabas S, Zeman F, Bendfeldt H, Rascle A, Deml L, Seelbach-Goebel B. 2017. Functional impairment of CMV-reactive cellular immunity during pregnancy. J Med Virol. 89:324.
Harwardt T, Lukas S, Zenger M, Reitberger T, Danzer D, Übner T, Munday DC, Nevels M, Paulus C. 2016. Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response. PLoS Pathog. 12(7):e1005748.

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)

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