University of Dundee

Developmental Biology

MRC DTP 4 Year PhD Programme: Functions & Applications of a Novel Stem Cell Signalling Pathway

The Findlay lab employs cutting-edge technologies to unravel Embryonic Stem (ES) cell signalling networks (Williams et al, Cell Rep 2016, Fernandez-Alonso et al, EMBO Rep 2017; Bustos et al, Cell Rep 2018), culminating in our recent discovery of the ERK5 pathway as an exciting new regulator of ES cell pluripotency. In order to uncover functions of ERK5 in ES cells, this project will deploy global proteomic and phosphoproteomic profiling. Novel ERK5 substrates and transcriptional networks will be characterised using biochemical and ES cell biology approaches.

MRC DTP 4 Year PhD Programme: Cell biology of a bacterial nano-weapon. Supervisors: Dr Sarah Coulthurst (Lead); Dr Colin Rickman (2nd Supervisor), Heriot-Watt

Many bacterial pathogens use the Type VI secretion system (T6SS) nanomachine to fire diverse, toxic ‘effector’ proteins directly into target cells. It is becoming increasingly apparent that the T6SS plays a key role in the virulence and competitiveness of diverse Gram-negative bacteria, including important human pathogens. Pathogens can use T6SSs to directly target eukaryotic organisms, as classical virulence factors. Alternatively, many pathogens can use T6SSs to target other bacterial cells, killing or inhibiting rivals.

MRC DTP 4 Year PhD Programme: Structural and developmental mechanics in polarized membrane trafficking

Membranes and their protein organization are a frontier in our understanding of cell biology. We will focus on polarized trafficking and asymmetric cell division as a model to uncover fundamental mechanisms in biology. This project aims to answer mechanistic questions in 1) the regulation of protein structural mechanics in polarized trafficking, 2) and the consequences and fundamental differences in this pathway’s organization between distinct tissues in development. Our philosophy is to address big-picture questions of challenging biology in a hypothesis-driven research project.

MRC DTP 4 Year PhD Programme: Proteomic approaches to understanding the role of IL-33 in immune mediated disease

While the immune system plays a critical role in combating infection, inappropriate regulation of immunity has a pathogenic role in many diseases including autoimmunity, allergic disease and cancer.  IL-33 is a member of the IL-1 family that is released by damaged endothelial and epithelial cells.  IL-33 release acts as a “danger” signal to activate inflammation.  It is involved in the response to both helminth and fungal infections and is also known to play a pathogenic role in allergic diseases such as asthma.  IL-33 acts on a subset of immune cells, including type 2 innate lymphoid cells

MRC DTP 4 Year PhD Programme: Regulation of Rab GTPases by the Parkinson’s associated PINK1 kinase

Parkinson’s disease (PD) is a leading cause of neurodegeneration in man. Mutations in the PINK1 kinase lead to autosomal recessive PD. Previous research in our lab has defined a cell signalling pathway for PINK1. Under basal conditions PINK1 is inactive however upon exposure to mitochondrial uncouplers that induce mitochondrial depolarization, PINK1 becomes stabilized and activated. Upon activation PINK1 phosphorylates a Parkinson’s disease-linked ubiquitin ligase, Parkin and ubiquitin.

MRC DTP 4 Year PhD Programame: Targeting protein degradation as an approach to inhibit oncogenes

Mutations or amplification of many oncogenes, such as Ras and Myc, have been known for up to 40 years to be drivers of many different cancers. Yet, effective ways of targeting these for inhibition with small molecules still do not exist. Consequently, together with several other oncogenes, these are often referred to as ‘undruggable’ targets. Targeted degradation of such oncogenes has the potential to make them ‘druggable’ targets and potentially lead to therapeutics. Recently, several strategies have been developed to selectively target the degradation endogenous proteins.