University of Dundee

Biochemistry

A candidate-gene approach for targeted identification of new parasite immunomodulators against allergic asthma.(Supervisors: Dr Henry McSorley (University of Dundee) and Dr Hermelijn Smits (Leiden University Medical Centre, the Netherlands)

This project will build on our knowledge of how parasitic helminths manipulate the host immune response, in a collaboration between the groups of Dr Henry McSorley (University of Dundee) and Dr Hermelijn Smits (Leiden University Medical Centre, the Netherlands). The successful candidate for this 4 year PhD position will spend significant time in both Dundee and Leiden, to identify, characterise and translate their findings.

Characterisation of enhancer DNA methylation and its impact in gene expression and disease

The School of Life Sciences at the University of Dundee is a world-class academic institution with a reputation for the excellence of its research, its high quality teaching and student experience, and the strong impact of its activities outside academia. With 900 staff from over 60 countries worldwide the School provides a dynamic, multi-national, collegiate and diverse environment with state-of-the-art laboratory, technology and teaching facilities.

MRC DTP 4 Year PhD Programme: Cell stress patterns and pathways in the mammalian embryo

Exposure to toxins from the environment has been linked to a rise in non-communicable diseases and behavioral deficits in adults. WHO data further indicate that deaths attributable to environmental factors are highest in children. Metabolic stress during embryonic development is also correlated with increased risk of type 2 diabetes, coronary artery disease and cancer as well as some psychiatric illnesses.

MRC DTP 3.5 Year iCASE Project: Machine learning to predict drug penetration into Gram-negative bacteria

An alarming rise in pathogens that show antibiotic resistance has been observed over recent years. In the case of Gram-negative bacterial pathogens, the resistance crisis has started to go out of control. Due to the lower permeability of the Gram-negative cell envelope for antibiotics, these pathogens are inherently more difficult to treat. The lower cell penetration of new drug candidates is also reflected in the failure of medicinal chemistry to advance novel classes of compounds with Gram-negative activity.

MRC DTP 4 Year PhD Programme: Dealing with proteotoxic stress: How do cells tidy up when trash piles up?

Degrading proteins in a timely manner to dispose of misfolded and damaged proteins is essential for a healthy cell. In ageing cells and organisms, there is a deterioration in the ability of cells to clear proteins resulting in the accumulation of misfolded proteins. Deposition of misfolded protein aggregates is a hallmark of many neurodegenerative diseases. It is not understood why quality control systems and the degradation capacity of a cell decline with age.

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

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