Investigating the role of endothelial cells in myelin damage in Alzheimer's diseases using iPSC-derived model

Alzheimer’s disease (AD) affects around 50 million people globally with no cure. Apart from well-known neuronal loss, myelin abnormalities in brain have been recently detected from early stage of AD. Myelin is formed by oligodendrocytes (OL) and it wraps nerve fibres facilitating rapid conduction and providing trophic support. It is still unclear what causes myelin damage in AD and whether reduced myelin and the number of OL contribute to the development of AD. OLs are regenerated from their progenitor cells (OPCs), the OPC-mediated remyelination process is vital for recovery from diseases and injuries, but the regenerative capacity declines with ageing. Endothelial cells (ECs) play important roles in the development, maintenance and regeneration of myelin. EC-secreted soluble factors, including growth factors and inflammatory mediators support the OPC proliferation and differentiation. ECs in AD are functionally altered and contribute to a noxious CNS milieu by releasing inflammatory and neurotoxic factors. It is unclear whether the altered EC-OPC/OL interaction in AD contributes the myelin loss.

The aim of the project is to elucidate whether EC’s dysfunction in AD actively contributing to CNS myelin damage. This will help us to gain insight into the causes of AD and reveal potential new targets for developing therapies. Induced pluripotent stem cells (iPSC) are a powerful tool to model human diseases. Our preliminary work has shown that iPSC-derived ECs promote OPC-mediated remyelination. The objective of the study is to assess the effect of ECs from AD patients on OPC functions and myelin integrity. We will use patient-derived iPSCs to produce ECs to model the EC-OPC/OL interaction in AD.

The PhD candidate will work in a multidisciplinary collaborative laboratory and receive training in a range of research techniques including cell culture, immunocytochemistry and immunohistochemistry, fluorescence microscopy and imaging analysis, ex-vivo brain slice models and antibody array.

Estimated yearly cost of consumables

£18,000

Person Specification

A Masters degree in a relevant subject with a 60% or higher weighted average, and/or a First or Upper Second Class Honours degree (or an equivalent qualification from an overseas institution)

Submitting an application

As part of the application, you will need to supply:

·        A copy of your current CV

·        Copies of your academic qualifications for your Bachelor degree, and Masters degree (if studied); this should include both certificates and transcripts, and must be translated in to English

·        A research proposal statement*

·        Two academic references

·        Proof of your English Language proficiency

Details of how to submit your application can be found here. 

*The application must be accompanied by a “research proposal” statement. An original proposal is not required as the initial scope of the project has been defined, candidates should take this opportunity to detail how their knowledge and experience will benefit the project and should also be accompanied by a brief review of relevant research literature.

Please include the supervisor’s name and project title in your Personal Statement.

If you require further information about the application process please contact the Postgraduate Admissions team at [Email Address Removed]