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How is viral DNA sensed by human cells?

  • Full or part time
  • Application Deadline
    Wednesday, January 01, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

The ability of a host to sense and respond to virus infection is largely dependent on the intracellular detection of viral nucleic acids. The DNA-sensing pattern recognition receptors (PRRs) that bind viral DNA and initiate the type-I interferon response are an essential component for mammalian host defence against DNA virus infections. The viral DNA-sensing PRRs cGAS, DNA-PK and IFI16 all function in human cells but how exactly they sense and respond to DNA virus infections is not well understood. This project aims to define the molecular mechanisms by which the pattern recognition receptors that sense the presence of viral DNA function to initiate and anti-viral response. We will use multiple methods in primary and immortalised human cells to characterise the signalling pathways downstream of DNA-sensing PRRs and the how they impact DNA virus infections.

Funding Notes

Funding* will cover the student’s stipend at the current Research Council rate and University Fees. The studentships will be funded for three years in the first instance subject to eligibility**, with the possibility of additional funding in the fourth year depending on circumstances.

**The studentships are available to students who qualify for Home/EU fees

Applications from ineligible candidates will not be considered.

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References

Ben J. Trigg, Katharina B. Lauer, Paula Fernandes dos Santos, Heather Coleman, Gabriel Balmus, Daniel S. Mansur and Brian J. Ferguson
The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection. Viruses 2018, Volume 9(11)
J Zinngrebe, E Rieser, L Taraborrelli, N Peltzer, T Hartwig, H Ren, I Kovács, C Endres, P Draber, M Darding, S von Karstedt, J Lemke, B Dome, M Bergmann , BJ Ferguson*, H Walczak* LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation. J Experimental Medicine 2016
BJ Ferguson, DS Mansur, NE Peters, H Ren, GL Smith. DNA-PK is a DNA sensor for IRF-3-dependent innate immunity. eLife Sciences, 2012, 1 e00047

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