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.
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.
Organisations
Publications
Schofield C
(2021)
Biochemical- and Biophysical-Induced Barriergenesis in the Blood Brain Barrier: A Review of Barriergenic Factors for Use in In Vitro Models
in Advanced NanoBiomed Research
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 |