Department of Biochemistry University of Oxford Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU

Tel: +44 (0)1865 613200
Fax: +44 (0)1865 613201
Image showing the global movement of lipids in a model planar membrane
Matthieu Chavent, Sansom lab
Anaphase bridges in fission yeast cells
Whitby lab
Lactose permease represented using bending cylinders in Bendix software
Caroline Dahl, Sansom lab
Epithelial cells in C. elegans showing a seam cell that failed to undergo cytokinesis
Serena Ding, Woollard lab
Collage of Drosophila third instar larva optic lobe
Lu Yang, Davis lab
First year Biochemistry students at a practical class
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Paul Elliott
Ubiquitin regulation of inflammatory signalling

Co-workers: TBA

A funded postdoctoral position is available in the lab and will be advertised soon

Our research investigates the molecular mechanisms by which ubiquitin regulates cellular processes, in particular inflammatory signalling pathways.

Post-translational modification of proteins provides a mechanism for rapid regulation of a broad range of cellular signalling pathways. The two main types of post-translational modifications are phosphorylation and ubiquitination. Ubiquitin regulatory versatility is achieved through the formation of a ubiquitin code. Dedicated 'writers' assemble the code, 'readers' decipher the code and 'erasers' reverse the code.

The ubiquitin code consists of at least eight different types of ubiquitin chains, each of which is determined by the linkage type between adjacent ubiquitin molecules. Covalent attachment to one of the seven internal lysine residues in ubiquitin forms Lys6, Lys11, Lys27, Lys29, Lys33, Lys48 and Lys63 linked chains, whilst covalent attachment to the amino-terminus forms Met1 linked chains.

These eight types of ubiquitin chains code for defined cellular functions, the most characterised being Lys48-linked ubiquitin chains that serve as a signal for protein degradation. Other chain types are emerging as crucial regulators of cell signalling pathways.

The importance of defined ubiquitin chains is underscored in inflammatory signalling pathways as defects in the ability to regulate Met1-linked ubiquitin chain abundance is causative of several human auto-inflammatory and immuno-deficiency diseases. Using an integrated structural, biochemical and biophysical approach, our lab investigates at the molecular level how the ubiquitin code regulates inflammatory signalling.

Publications

  1. Elliott PR. (2016) Molecular mechanisms underlying Met1-linked polyubiquitin specificity. Biochem Soc. Trans. 44 (6) 1581-1602.
     
  2. Elliott PR, Leske D, Hrdinka M, Bagola K, Fiil BK, McLaughlin SH, Wagstaff J, Kessler BM, Freund SMV, Komander D, Gyrd-Hansen M. (2016) SPATA2 links CYLD to LUBAC, activates CYLD and controls LUBAC signalling. Mol. Cell 63 (6) 990-1005.
     
  3. Michel MA$, Elliott PR$, Swatek KN, Simicek M, Pruneda JN, Wagstaff JL, Freund SMV, Komander D.(2015) Assembly and binding of K33-linked polyubiquitin. Mol. Cell 58 (1) 95-109.
     
  4. Elliott PR, Nielsen SV, Marco-Casanova P, Fiil BK, Keusekotten, K, Freund SMV, Gyrd-Hansen M, Komander D. (2014) Molecular basis and functional consequences of OTULIN-LUBAC interaction. Mol. Cell 54 (3) 335-348.
     
  5. Keusekotten K$, Elliott PR$, Glockner L, Fiil BK, Damgaard RB, Kulathu Y, Wauer T, Hospenthal MK, Gyrd-Hansen M, Krappmann D, Hofmann K, Komander D. (2013) OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin. Cell 153 (6) 1312-1326.
More Publications...

Research Images

Figure 1. The two major types of post-translational modifications - phosphorylation and ubiquitination - are regulated by analogous cycles of ‘writers’, ‘readers’ and ‘erasers’. (Click to Enlarge)

Figure 2. The importance of defined ubiquitin chains in regulating cellular processes is underscored in inflammatory signalling pathways. (Click to Enlarge)
 

Figure 3. The ubiquitin code controls many cellular processes. (Click to Enlarge)
 

Figure 4. Our lab uses an integrated approach to understand molecular mechanisms of ubiquitin signalling. (Click to Enlarge)
 







 

Contact: paul.elliott@bioch.ox.ac.uk

Graduate Student and Postdoctoral Positions:

Undergraduate/Master's/PhD/Postdoctoral researcher enquiries are all welcome.
A funded postdoctoral position is available in the lab and will be advertised soon.