Engineering the blood-brain-barrier

Lead Research Organisation: University of Glasgow
Department Name: School of Engineering

Abstract

Blood-brain-barrier (BBB) dysfunction is associated with key neurodegenerative diseases affecting our aging population, including Alzheimer's and Parkinson's disease. The BBB consists of specialised endothelial cells (ECs) that are separated by a thin basal lamina from a layer of associated pericytes and astrocytes. Astrocyte secrete cytokines and growth factors that increase the tightness of the endothelial layer.
This project will engineer a novel, simple yet robust in vitro model of the BBB that reproduces the main features of the physiological unit by substituting astrocytes/pericytes by a bioengineered membrane that presents growth factors very efficiently. This would facilitate screening for novel BBB treatments by pharma as well as the investigation of disease mechanisms.
The project is highly multidisciplinary and involves 3D printing, surface functionalisation with proteins and cell biology at the interface with materials.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509668/1 30/09/2016 29/09/2021
2126460 Studentship EP/N509668/1 30/09/2018 30/03/2022 Christina Schofield
EP/R513222/1 30/09/2018 29/09/2023
2126460 Studentship EP/R513222/1 30/09/2018 30/03/2022 Christina Schofield
 
Description We have shown that endothelial cells grown on our labs coated membranes generate the proteins we would associate with endothelial cells found in the blood brain barrier. We can quantify that this is achieved better using the coatings, and then do some further experiments to see what growth factors might make even better barriers. This can hopefully eventually be used to model diseases or disruption of the blood brain barrier, and as an initial test of whether drugs targeting the brain may be able to pass through the blood brain barrier.
Exploitation Route Our model has already been sent to two collaborators, one which works on the devastating brain cancer glioblastoma, whose treatment is vastly hindered by the blood brain barrier, as well as a group workingnn on the epithelial barrier in the lungs, which we think our base model of the insert + membrane + coatings should help improve. We are also always looking for further collaborators.

The findings from the project have also aided similar vascular-related projects within the lab.
It is the hope that the outcome of this lab will be a functional, simple and easy to use model of the blood brin barrier which others can use to test the potential of new drugs to enter the brain in the early stages of drug development, to model disease (as well as using patient-specific cells to more accurately capture what might be occuring within their anatomy) and generally be used to understand the molecular complexity within the blood brain barrier.

The hope that this project will lead to a useful paper which in turn can better help the blood brain barrier community as whole, as this simple model may make entry-level blood brain barrier research more achielable
Sectors Healthcare

Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology

 
Description 3MT - Three Minute Thesis competition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Partook in the 3MT competition, presenting my PhD work in 3 minutes to an audience of other PhD students. A lot of people asked me further questions during the break about my research.
Year(s) Of Engagement Activity 2019,2020,2021
 
Description Biomaterials Weekly Meetings 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Have given three talks at the weekly Biomaterials meetings, presenting work to other biomaterial researchers at the University of Glasgow.
Year(s) Of Engagement Activity 2018,2019,2020,2021
 
Description Demonstrator 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Helped with undergraduate lab for bioengineering students at the university of glasgow, and helped them understand the cell-based and hyrdogel reseach which our lab does. Sparked some very good questions from the students, several of which undertook summer internships in our/related labs based on the lab.
Year(s) Of Engagement Activity 2019,2020
 
Description Podcast: CeMi Serious Sciene 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Formed a lab podcast named CeMi Serious Science with colleague and fellow PhD student Stylianos Orestis Sarrigiannidis, in which we interview people in STEM about their work and life in a way that should be engaging for someone without a background in scicence.

For this activity, Styli and I's role is asfollows: reaching out to poential guests for the podcast, researching guests and writing questions, performing and recording the interview, and editing the podcast episode for release.

CeMi Serious Science is released on PodBean, Stitcher, Apple Podcasts and Spotify, where on average each episode gets 200-300 listens (although listenership is increasing).

We also engage with the public through the podcast Instagram, Twitter and Reddit account, answering questions and asking if the public havbe any questions for our up and coming guests.
Year(s) Of Engagement Activity 2019,2020,2021
URL https://open.spotify.com/show/7GwwKi050CpsTrVznRxtGw
 
Description Poster presentation at the GLORI symposium 2020 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact I had the opportunity to present my work in poster form at the GLORI symposium in Glasgow. This was an excellent oppportunity to share my work as well as recieving good feedback on further useful experiments.
Year(s) Of Engagement Activity 2020
 
Description Presentation at MiniGLORI 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Gave presentation at MiniGLORI symposium at the University of Glasgow, which sparked interesting discussions and increased questions on my research aroiund the lab.
Year(s) Of Engagement Activity 2019
 
Description Showed prospective students around lab 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Showed prospective undergraduate students around research lab (specifically the electrospinning equipment) and answered questions concerning my research, the work the lab does, and pursuing a degree at the Univerisity of Glasgow.
Year(s) Of Engagement Activity 2018,2019
 
Description Talk at World Biomaterials Conference 2020 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Gave 12 minute talk at the WBC online conference 2020, for which I won an award from the European Society for Biomaterials. To date, 51 people have watched my presentation.

Recieved some interest questions and got to engage with people in BBB research.
Year(s) Of Engagement Activity 2020