University of Dundee

Biochemistry

MRC DTP iCASE PhD Project: Developing novel biophysical and cellular assays to study small-molecule mediated protein ubiquitination and degradation

Bifunctional degrader molecules also known as Proteolysis Targeting Chimeras (PROTACs) and the mechanistically related monovalent degraders (for example auxin, lenalidomide and indisulam) work by co-opting an E3 ubiquitin ligase to act upon a neo-substrate protein. Formation of a ternary complex species between the E3 ligase, the degrader molecule and the target protein leads to the latter being ubiquitinated and subsequently degraded by the proteasome.

MRC DTP iCASE PhD Project: Characterisation of novel niraparib resistance mechanisms in ovarian cancer

We invite applications from outstanding biological or biomedical sciences graduates for a fully-funded 3.5-year MRC Doctoral Training Programme iCASE PhD studentship, in collaboration with GlaxoSmithKline (GSK), starting in September 2020, based in the Jacqui Wood Cancer Centre in the University of Dundee School of Medicine, Ninewells Hospital & Medical School.

CSC - Developmental role of jasmonate in barley

Most of our food calories come from cereal grain. The development of cereal plants strongly influences the amount of harvested grain or its yield.  Cereal stems elongate when they flower (1). Tall cereals easily fall over, a devastating event for farmers, so controlling cereal height is important for cereal breeders. We recently discovered that jasmonate, a classic plant stress/defense hormone, strongly inhibits both flowering and stem elongation in barley (2), suggesting that the jasmonate pathway may be a good breeding target.

CSC - Phosphorylation of Rab GTPases in Health & Disease

Phosphorylation is a major posttranslational modification whose disruption is linked to multiple human diseases. Our lab has recently found a link between the Parkinson’s associated protein kinase PINK1 and a subset of Rab GTPases. This project will employ state-of-the-art methods to uncover the regulation of Rabs by PINK1 in cells .

The project will lead to training in a wide array of technologies including mass spectrometry and biochemistry. The lab is also linked to the EMBO network and the student will also benefit from training opportunities in Europe during their studies.

CSC - How does the HOIL-1 component of LUBAC regulate innate immunity?

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].

CSC- Non-lysine ubiquitination in health and disease

Ubiquitination is a posttranslational modification that regulates all aspects of physiology and aberrant ubiquitination has been implicated with numerous diseases. Ubiquitination is typically considered a posttranslational modification of lysine residues but it is emerging that non-lysine ubiquitination is intrinsic to mammalian biology. This project will use a multidisciplinary approach to understand the cellular function of non-lysine ubiquitination.

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