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.
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.
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.
Supervisors: Dr Colin Murdoch, School of Medicine/Systems Medicine and Dr Colin Henderson, School of Medicine/Systems Medicine.
In barley and wheat substantial proportions of the chromosomes are inherited together as a large linkage block, preventing the generation of novel gene combinations and useful variation that could be exploited in breeding and genetics programs. In these crops, the distribution of meiotic crossover events is skewed toward the telomere regions meaning that up to half of the genes rarely if ever recombine.
To maintain their genetic integrity, eukaryotic cells must segregate their chromosomes properly to opposite spindle poles during mitosis. This process has important medical relevance because chromosome mis-segregation plays causative roles in human diseases such as cancers and congenital diseases. To prepare for proper chromosome segregation, kinetochores – the spindle attachment sites on chromosomes – must correctly interact with spindle microtubules (MTs) during early mitosis.
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.
Diabetes and chronic heart failure (CHF) often coexist such that each condition may affect the other in terms of causation and outcome. This bidirectional interrelationship between CHF and diabetes also extend to insulin resistance. Insulin resistance and associated reductions in cardiac insulin signalling is emerging as a major factor for the development of CHF. The pathogenesis of insulin resistance in CHF is not fully understood. A growing body of evidence suggests a link between extracellular matrix (ECM) remodelling and insulin resistance.
Increasing evidence shows that alterations and mutations in the UPS give rise to various human diseases, such as cancer and neurodegenerative disorders. Our interest is to understand how the activity of the ubiquitin-proteasome system is regulated in cells so that accumulation of unfolded, misfolded, or damaged proteins can be cleared before they become deleterious (Rousseau and Bertolotti, 2018, Nature Reviews Molecular Cell Biology).
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.