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China Scholarship Council: How does the HOIL-1 component of LUBAC regulate innate immunity?

  • Full or part time
    Prof Sir Philip Cohen
  • Application Deadline
    Wednesday, January 15, 2020
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

The School of Life Sciences at the University of Dundee, joint with the China Scholarship Council (CSC), is proud to be able to offer a scholarship programme for postgraduate research students. The scholarship covers all tuition fees and research fees and provides living expenses and one return flight ticket to successful candidates. There are up to 5 scholarships of 4 years duration available.

The Linear Ubiquitin Assembly Complex (LUBAC) contains two E3 ubiquitin ligases, called HOIP and HOIL-1. HOIP catalyses the formation of Met1-linked ubiquitin (also called linear ubiquitin) chains, which are required to activate the IkB kinase (IKK) complex that switches on the master transcription factors of the innate immune system, NF-kB and IRF5 (interferon regulatory factor 5). In contrast, we have recently discovered that HOIL-1 is a remarkable and most unusual E3 ligase that links ubiquitin to serine and threonine residues in proteins by forming ester bonds [1]. We have also found that the physiological substrates of HOIL-1 include the components of the Myddosome, an oligomeric complex that initiates signaling by Toll-Like Receptors (TLRs) and members of the Interleukin-1 (IL-1) family of cytokines. This exciting finding has opened up several new projects that would make interesting and challenging PhD projects. For example, how do HOIL-1-catalysed ester bonds control the production of inflammatory mediators by the innate immune system? Are other innate immune signaling pathways, such as those triggered by TNF or NOD-like receptors, also regulated by HOIL-1? Which deubiquitylases hydrolyse the ester-linked ubiquitins formed by the action of HOIL-1, and are ester-linked ubiquitins recognized by novel ubiquitin-binding proteins that decode their message? These projects will be tackled by a range of “state-of-the art” methods in my laboratory that include protein chemistry and mass spectrometry, cell and molecular biology, immunology and mouse genetics.

Funding Notes

In order to be eligible for these awards applicants must:

Be a Chinese national
Meet the requirements of the CSC – please see their website
Hold an unconditional offer to study for a PhD at the University of Dundee and meet our English language requirements
Have completed bachelors or masters degree before the agreed start of PhD study.

References

Reference.

Kelsall, I.R., Zhang, J., Knebel, A., Arthur, J.S.C. and Cohen, P. (2019) Proc.Natl. Acad. Sci. USA 116, 13293-13298. The E3 ligase HOIL-1 catalyses ester bond formation between ubiquitin and components of the Myddosome in mammalian cells.

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