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Ubiquitin signalling mechanisms: From decoding to functional responses

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

The cells in our body use signal transduction pathways to communicate external stimuli and stress to produce an appropriate functional response. The information flow in signalling pathways is mediated by posttranslational modifications (PTMs). Ubiquitylation is an important PTM that regulates almost every facet of eukaryotic biology. This is made possible because different types of ubiquitin (Ub) signals can be generated and the type of signal depends on whether Ub is attached to a protein as a single molecule (monoUb) or as a polyubiquitin (polyUb) chain. PolyUb chains of 8 different types can be formed depending on the lysine within one Ub molecule that connects to another Ub within the chain. In addition, we and others have recently shown that mixed or branched polyUb chains can be formed. These diverse types of Ub modifications encode different signals, thus making ubiquitylation a very information rich system.

The central question we are addressing is how this vast array of different Ub signals are decoded and coupled to downstream signalling to produce specific cellular responses. My lab is interested in how Ub signals regulate immune responses and how they are deregulated in immune disorders. We also study how different Ub signals regulate removal of damaged or misfolded and aggregated proteins and how they are deregulated in age-related diseases such as Alzheimer’s or Huntington’s disease.

The PhD project is likely to focus on one of these broad areas and the precise project will be decided together with the student to match their research and methodological interests. We employ a range of techniques including state-of-the-art ubiquitin proteomics, X-ray crystallography, mouse models and CRISPR/Cas genome-editing methods in our research for a comprehensive mechanistic and functional understanding.

Further details of our research are at http://www.ppu.mrc.ac.uk/research/?pid=1001&sub1=research .

Informal enquiries can be made to

Funding Notes

We offer a 4 year studentship in which you would join a particular lab in the Unit. However, we strongly encourage prospective students to become part of the 4-year PhD programme in which you carry out rotation projects in two labs within the Unit (View Website). This studentship is jointly funded by the Medical Research Council and the University of Dundee and carries a tax-free stipend of £20,000 per annum

References

1. Kristariyanto, Y. A. et al. Mol Cell 58, 83–94 (2015).
2. Meyer, H.J. & Rape, M. Cell 157, 910–921 (2014).
3. Popovic, D., Vucic, D. & Dikic, I. Nat Med 20, 1242–1253 (2014).

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