University of Dundee

MRC Doctoral Training Programme

MRC DTP - Investigating protein acylation as a nutrient-sensitive mechanism controlling insulin secretion in pancreatic beta cells

Regulated insulin secretion from pancreatic beta cells is essential for metabolic homeostasis. Beta cell dysfunction/failure is a hallmark of both major forms of diabetes1, resulting in hyperglycaemia and many associated complications. Diabetes affects 463m people worldwide (expected to rise to 700m by 2045; www.idf.org)  and is a major burden on quality of life, productivity and healthcare expenditure (~10% of the NHS budget).

MRC DTP: Accessible machine learning in behavioural neuroscience to address the 3Rs challenge

Behavioural neuroscience using rodent models is an established and essential area of biomedical research, but one which can be high cost in terms of time, finances and animal welfare. At the forefront of modern animal research is the need to address the principles of the 3Rs- Replacement, Reduction and Refinement.

MRC DTP iCASE: High-Resolution Fast Hydrogen Deuterium Exchange Mass Spectrometry for the Characterisation of GCN2 activation. Supervisors: Dr G Masson; Dr Adrian Saurin (Medicine)

The eIF2a kinase GCN2 is an amino acid starvation sensing protein, and is a therapeutic target in cancer, diabetes, and myocardial infarction. However, its structure and mechanism of activation are poorly understood1. When proteins are activated, they often become more flexible as autoinhibitory intramolecular interactions are broken, making structural characterisation more difficult. In this project both two complementary tools – hydrogen deuterium exchange mass spectrometry (HDX-MS) and nanobodies will be used together to facilitate insight into GCN2 activation.

MRC DTP iCASE: Using artificial intelligence to identify and dissect candidate conveyors of OGT-linked intellectual disability

Protein O-GlcNAcylation is an essential posttranslational modification of Ser/Thr residues on nucleocytoplasmic proteins with N-acetylglucosamine (GlcNAc). It is regulated by two opposing enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). OGT catalyses O-GlcNAcylation and possesses a catalytic domain and N-terminal tetratricopeptide repeats (TPRs) that mediate substrate recognition.

MRC DTP: Defining the crosstalk between transcription factors NRF2 and HSF1: Implications for Parkinson’s disease

With ageing of the population, the prevalence of neurodegenerative disorders and the associated socioeconomic burden have dramatically increased. New therapeutic and prevention strategies are urgently needed. The prevalence of Parkinson's disease (PD) is projected to double by 2030, and there are no effective disease-modifying therapies to date1.

MRC DTP: Detecting phenotypes in a mouse model of O-GlcNAc-linked intellectual disability: Supervisors; Prof Daan van Aalten ; Dr A McNeilly

Protein O-GlcNAcylation is an essential posttranslational modification of Ser/Thr residues on nucleocytoplasmic proteins with N-acetylglucosamine (GlcNAc). It is regulated by two opposing enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) (Fig. 1). OGT catalyses O-GlcNAcylation and possesses a catalytic domain and N-terminal tetratricopeptide repeats (TPRs) that mediate substrate recognition. Ogt is X-linked in vertebrates and is required for mouse embryogenesis.

MRC DTP: Quantitative approaches to cell polarity regulation

This PhD project will combine mathematical modelling and experimental approaches in order to understand the spatiotemporal dynamics that regulate asymmetric cell division. Asymmetric cell division is a fundamental process that generates cellular diversity.  Moreover, stem cells in higher organisms can polarise and segregate evolutionarily conserved fate determinants unequally to the resulting daughter cells that then undergo different developmental programs.

MRC DTP: Functions & Applications of a Novel Stem Cell Signalling Pathway

The Findlay lab employs cutting-edge technologies to unravel Embryonic Stem (ES) cell signalling networks, culminating in our discovery of the ERK5 pathway as an exciting new regulator of ES cell pluripotency (Williams et al, Cell Reports 2016; Brown* Williams* et al, in preparation). In order to uncover functions of ERK5 in ES cells, this project will deploy global proteomic and phosphoproteomic profiling.

Pages