White matter really matters in cerebral Small Vessel Disease: WNT signalling in the endothelial – oligodendroglial crosstalk

Research interests/description of main research theme:
The PhD candidate will work at the interface between cardiovascular and neuro-sciences as part of a joint project between Maastricht University and the University of Birmingham. This project is focused on the crosstalk between endothelial cells and oligodendrocytes (OL) via WNT signalling in the context of cerebral small vessel disease (cSVD).
Neurodegenerative diseases represent a critical challenge to society due to population ageing, amongst which cSVD provides a promising area for therapeutic intervention because of its well-known cardiovascular risk factors (e.g. ageing, hypertension, diabetes). cSVD impairs cognitive function, and is characterized by the presence of lesions in myelin-rich white matter regions (WML) and Blood Brain Barrier (BBB) leakages, amongst other structural abnormalities. This indicates that oligodendrocytes (OL), the cells responsible for generating and supporting myelin, are especially vulnerable to injury in this condition. While the development of WML in cSVD is influenced by hypertension and other cardiovascular risk factors, specific mechanisms causing WML have not been investigated.
The production of myelin during development places a major metabolic demand on OL and its precursors (OPCs) that must be satisfied by a sufficient blood supply. WNT signalling is critically important for developmental processes including blood vessel and blood brain barrier formation. It also mediates complementary actions to ensure the proper adjustment of OPC/OL function based on the oxygen and nutrients supply. The relevance of such mechanism in cSVD is unknown, but could explain the burden of WML and the presence of BBB leakages occurring from the newly formed, immature, leaky blood vessels.

In this project, the PhD student will study WNT signalling in OL/OPC, and its crosstalk with endothelial cells, to identify potential therapeutic strategies to limit BBB leakages and preserve myelin integrity in cSVD.
Role description
• Design and performs scientific research;
• Works in a team with PhD students, scientists and clinicians;
• Discuss plans and performs research in a stimulating environment;
• Work in a highly international research group across two different sites: University of Birmingham and Maastricht University.

Requirements
Applicants must be European residents, achieve the required University of Birmingham IELTS score (average 6.5 overall and no less than 6.0 in any one category), and be willing to spend 1.5 year in each University. The successful candidate will be registered as a PhD student at Birmingham University and will also be registered at Maastricht University. The graduation will result in a joint PhD degree from the two universities.
• Honours degree (2:1 or 1st class) in molecular life sciences, biomedical sciences, medical biology, neurosciences or a related discipline;
• Strong background in vascular and/or neuroscience research and/or pharmacology is an asset;
• Certification to work with animals and experience with conducting animal studies is an asset;
• Experience with cell culture work and molecular biology techniques is required;
• Highly motivated to work in an interdisciplinary environment;
• Excellent interpersonal and communication skills are essential;
• Willingness to work flexibly;

How to apply
Informal enquiries should be directed to Dr Zubair Ahmed ([Email Address Removed]), Dr Daniel Fulton ([Email Address Removed]); [Email Address Removed]
To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.