3D Biomaterials for a Blood Brain Barrier Vasculature Model

Aston Institute for Membrane Excellence

This studentship is supported by the Aston Institute for Membrane Excellence. AIME is a unique, interdisciplinary, intersectoral research and training hub for translational membrane science. AIME is a globally unique, cross-disciplinary institute to develop novel membranes for use in applications as varied as drug discovery and water purification. The team behind AIME believes that the full potential of membranes will only be realised by a research team spanning biology, physics and chemistry that can investigate membranes holistically. No other institute has the platform, potential or promise for major breakthroughs in this area. The vision is for AIME to become a ‘one-stop shop’ for interdisciplinary, translational membrane research through access to its facilities and expertise, ideally located in the heart of the UK.

Details of the Project

The blood brain barrier (BBB) is a complex structure providing nutrient exchange throughout the central nervous system (CNS); this is vital for the maintenance of homeostasis and functionality. Changes to the BBB are hallmarks of a variety of devastating neurological disorders, such as traumatic brain injury (TBI) and Alzheimer’s disease (AD). Modelling these changes is therefore necessary to understand disease progression, and how it can be predicted, prevented or reversed. The biological community is currently moving towards using 3D in vitro models that are built using human cells, as animal models do not fully recapitulate human processes. 3D models are more physiological than standard 2D cultures, allowing cells to be in a more native conformation with physical cues from all angles.

Currently, the BBB is modelled using ex vivo tissue or by 2D in vitro culture, limiting the relevance to the human 3D in vivo environment. Here we will produce a fully 3D human in vitro model using micro-hollow fibre biomaterial scaffolds. These structures will provide the support the cells need, whilst also allowing for the functional diffusion required, due to their porous structure. They will be modifiable to enhance cell attachment, maturation and function through chemical modification, and will also be optimised to be biodegradable. This will result in a material free system once the cell structures have been formed; removing biomaterial scaffolds between cells will allow for native cell connectivity and therefore function. This important challenge will require optimisation of the chemical composition of the fibre to form a stable model before removal.

The project will use micro-hollow fibres with human endothelial cells, pericytes and astrocytes to produce a BBB model that can be used to interrogate BBB functionality before and after damage and disease. This model is unique due to the inclusion of relevant human cell types, along with appropriate flow. The mechanical forces on the cells will alter their maturation and functionality, mimicking the in vivo mechanical environment.

The successful candidate will optimise a novel micro-hollow fibre, making changes to the material, diameter, porosity, degradability and flow rate. These parameters will be tuned to closely mimic the physiology and pathophysiology of the CNS vasculature. The student will validate the model by assaying cell functionality with and without flow. BBB permeability will be measured using a fluorescent probe such as fluorescein isothiocyanate-labelled dextran. Tight-junction formation will be measured by immunocytochemistry.

Introduction of fibre degradability, via materials selection, will allow for the development of unsupported models. Further optimisation will be done with a Quantum x Bio 3D bioprinter once sufficient optimisation has been performed with the current methods. Metabolic and functional assessments will be undertaken to determine what is able to pass through the barrier, and how the cells are functioning when compared with a planar culture and the current BBB in vitro models.

Throughout this project, the student will be working at the cutting edge of the field of 3D models of the BBB, using state of the art equipment and advancing their own knowledge and that of the scientific community. This will give them the tools and skill to go beyond this PhD into academia, industry or many other career destinations.

Person Specification

The successful applicant should have been awarded, or expect to achieve, 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) in a relevant subject. Previous experience in stem cell culture Interdisciplinary working would be desirable.

Contact information

For formal enquiries about this project contact David Jenkins at d.jenkins10@aston.ac.uk

Submitting an application

We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected. Your application must include:

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor degrees.
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count.
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience.
4. Two academic referees who can discuss your suitability for independent research. References must be on headed paper, signed and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary.
5. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage.
6. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Apply for this position here

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Please select “ Research – Biomedical Sciences” from the application form options.

If you require further information about the application process, please contact the Postgraduate Admissions team at pgr_admissions@aston.ac.uk