PhD studentship in Urbé lab

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PhD Studentship: The flipside to Parkin – regulation of mitochondrial deubiquitylase activity

£14,057 stipend 3 years PhD Studentship, due to funding, only Home/Eu Students are eligible to apply.

Faculty of Health and Life Sciences, Institute of Translational Medicine, Celluar and Molecular Physiology

Location: University Campus

Ref: PHD-URBE-PARKIN/WWW

Closing date for receipt of applications: Thu, 21 Jan 2016 17:00:00 GMT

 

The PhD project concerns the role of deubiquitylases or DUBs in the process of Parkin-mediated mitophagy. Parkin is an ubiquitin E3-ligase that mediates the clearance of defective mitochondria by ubiquitylating mitochondrial outer membrane proteins. These act as scaffolds for the recruitment of the autophagy machinery. Parkin loss of function mutations have been associated with Parkinson’s disease, presumably due to an increased ROS-burden in dopaminergic neurons of the substantia nigra leading to cell death. Deubiquitylases that oppose Parkin activity are potential therapeutic targets to rescue inefficient mitophagy in a Parkinson’s disease setting. The PhD student will join a dynamic team of cell and molecular biologists working at the interface of neurobiology and cancer research.

You should have, or expect to hold a first or upper second class honours degree in a relevant discipline. Laboratory experience is desirable but not essential.

1. USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death.

Liang JR, Martinez A, Lane JD, Mayor U, Clague MJ, Urbé S.

EMBO Rep. 2015 May;16(5):618-27. doi: 10.15252/embr.201439820. Epub 2015 Mar 4.

2. Ubiquitin code assembly and disassembly.

Heride C, Urbé S, Clague MJ.

Curr Biol. 2014 Mar 17;24(6):R215-20. doi: 10.1016/j.cub.2014.02.002. Review.

3. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy.

Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q, Foreman O, Kirkpatrick DS, Sheng M.

Nature. 2014 Jun 19;510(7505):370-5. doi: 10.1038/nature13418. Epub 2014 Jun 4.

Including Highlight: Cell biology: balancing act. Ordureau A, Harper JW.

Nature. 2014 Jun 19;510(7505):347-8. doi: 10.1038/nature13500. Epub 2014 Jun 4.

4. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease.

Pickrell AM, Youle RJ.

Neuron. 2015 Jan 21;85(2):257-73. doi: 10.1016/j.neuron.2014.12.007. Review.

4.Deubiquitylases from genes to organism.

Clague MJ, Barsukov I, Coulson JM, Liu H, Rigden DJ, Urbé S.

Physiol Rev. 2013 Jul;93(3):1289-315. doi: 10.1152/physrev.00002.2013. Review.

 

To apply please send a cover letter summarising your motivation and interest in the project, as well as a CV including details of at least two referees to urbe@liv.ac.uk. For application enquires please contact Sylvie Urbé (urbe@liv.ac.uk)