Postdoctoral Research Assistant - MRC PPU - UOD2185

MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU):

The MRC PPU is one of the world’s most renowned centres for research on protein phosphorylation and ubiquitylation (www.ppu.mrc.ac.uk). Many world-leading researchers in the field of signal transduction have trained within the MRC PPU. The major aims of the MRC PPU are to advance understanding of the role of protein phosphorylation and ubiquitylation in cell regulation and human disease, to facilitate the development of drugs to treat diseases caused by abnormalities in phosphorylation, and to generate reagents and improve technologies.

The Project: Identification of Cellular Substrates and Functions for Atypical E3 Ligases

We are recruiting for an exceptional individual to join us as a Postdoctoral researcher within our MRC Protein Phosphorylation and Ubiquitylation Unit. This is a fixed-term appointment for 36 months.

Background: The traditional view of the ubiquitin-proteasome system (UPS) centres on the formation of isopeptide bonds between the C-terminus of ubiquitin and substrate lysine residues. However, recent breakthroughs have identified a "non-lysine" frontier. We are seeking a highly motivated Postdoctoral Research Assistant to investigate the biochemical mechanisms and cellular roles of MYCBP2 (a threonine-directed ester-E3) and RNF213 (a lipid-directed E3).

The Role: The successful candidate will utilise a multidisciplinary approach combining advanced mass spectrometry workflows, cell biology and biochemistry to:

• Develop and deploy new technologies to enrich and identify novel ester-linked or non-proteinaceous ubiquitin conjugates.
• Characterise the "atypical ubiquitome" of MYCBP2 and RNF213 in response to neurotrophic factors and immunological stress.
• Elucidate the structural basis for substrate recognition and non-canonical chemistry using biochemical analysis

Requirements:

• A Ph.D. in Biochemistry, cell biology, or a related discipline.
• Expertise in biochemistry, mammalian cell biology and structural biology.
• Experience with E3 ligase biochemistry or Ubl-signaling.
• A strong publication record.

We Offer:

• Access to state-of-the-art life science facilities including MS-proteomics and cryo-EM.
• A collaborative environment for multidisciplinary research.
• Support for independent fellowship applications.

1. Squair, D.R., Virdee, S. A new dawn beyond lysine ubiquitination. Nat Chem Biol 18, 802–811 (2022),

doi.org/10.1038/s41589-022-01088-2.

1. Pao et al. Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity. Nature 556, 381-385

(2018), doi:10.1038/s41586-018-0026-1

1. De Cesare et al. Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases. Proc Natl Acad

Sci U S A. 118(4):e2006947118 (2021), doi: 10.1073/pnas.2006947118.

Your priorities will include:

• Molecular biology-based molecule cloning and construct design
• Design and implementation of engineered cell lines
• Development of novel PTM enrichment workflows for mass spectrometry
• Biochemical and structural characterisation
• Maintenance of lab records comprehensive

What we’re looking for:

• Experience with the ubiquitin system
• Experience with biochemistry and cell culture methods
• Excellent communication skills

For further information about this position please contact Satpal Virdee at s.s.virdee@dundee.ac.uk. To find out more about MRC PPU please visit www.ppu.mrc.ac.uk

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