Application deadline: 3rd March
Interviews to be held: 31 March 2021
Dysregulation of the blood-brain barrier (BBB) is an early and critical event in the pathogenesis of neurovascular diseases, such as Alzheimer’s disease, vascular dementia and stroke. However, there is a lack of knowledge of the molecular and cellular mechanisms underlying the breakdown of the BBB in these diseases due to the difficulty in studying the BBB in vivo. The multicellular neurovascular unit (NVU) is central to the regulation of BBB function in health and its dysfunction in neurovascular diseases. The NVU comprises endothelial cells, pericytes, astrocytes and neurons. Complex and dynamic interactions between these cells and the surrounding extracellular matrix (ECM) regulate BBB (dys)function.
This project will focus on incorporating hydrogels that mimic the physical and chemical properties of the brain ECM, 3D bioprinting and microfluidic technology to recapitulate the capillary blood flow, along with the co-culture of human induced pluripotent stem cell (iPSC)-derived endothelial cells, pericytes, neurons and astrocytes, to reverse engineer a 3D BBB model. This reverse engineered BBB model will be used to investigate the pathological neurovascular dysfunction underlying Alzheimer’s and vascular dementia and for studying the transport efficacy of drugs that target the brain.
Main question to be answered
1) what is the most appropriate natural hydrogel that recapitulates the in vivo mechanical (stiffness, elasticity and viscosity) and biochemical (cell adhesion) properties and supports the growth of the multiple NVU cell types?
2) what is the effect of alteration of the ECM (e.g. increased stiffness, reduction in proteoglycan content) on BBB function and amyloid deposition?
3) will alteration of protein activity lead to alterations in BBB integrity and amyloid deposition, and what are the molecular mechanisms underlying this?
EPSRC Centre for Doctoral Training in Advanced Biomedical Materials
This project is part of the EPSRC Centre for Doctoral Training in Advanced Biomedical Materials. All available projects are listed here.
Find out how to apply, with full details on eligibility and funding here.
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