Develop synthetic extracellular matrix for engineering defined 3D human neural tissue

Commercial partner: PeptiMatrix

Extracellular matrix (ECM) constitutes around 20% of the adult brain volume and plays an important role in brain function and disease. Increasing evidence suggests there are significant ECM changes, including degradation, overproduction and composition alteration, during the development of neurodegenerative disease. 3D tissue models including organoids are powerful tools to model human development and diseases. However, organoids are largely heterogenous and rely on the use of mouse-tumour-derived hydrogels, such as Matrigel. Matrigel is not defined, varies from batch to batch, and has limited potential for applications in the clinic.

To engineer defined 3D neural tissues, we will combine 3D bio-printing with chemically defined hydrogels. Previously we have developed a 3D printing technique to fabricate 3D human neural tissues for disease modelling and tissue repair using iPSCs derived neurons. We will collaborate with PeptiMatrix to design and synthesise novel chemical-defined, peptide-based hydrogels. These hydrogels will be tested to tailor the hydrogel properties to match brain tissue, such as mechanical (e.g. stiffness) and structural properties (e.g. pore size). Compatibility with our 3D printing techniques will also be optimised. The protein motifs of key brain ECM components, such as collagen IV and fibronectin, will be incorporated into the synthetic hydrogel. Different combination and ratio of these motifs will used to test their effects on neural cells. The ability of the hydrogels to support the survival, maturation and function of the iPSC-derived 3D neural tissues will be examined and quantified. Further, we will test the hydrogels with neural cells derived from patients with Parkinson’s disease. The changes of the hydrogels during the culture with healthy and diseased neural cells will also be examined. The developed hydrogels will be defined and compatible with neural tissues to maximise the breadth of potential applications in research and in the clinic.

The proposed project is highly multidisciplinary and aligns with MRC’s research priorities in developing new techniques for neuroscience and for tackling brain diseases such as neurodegeneration. Developing new tools to address neurodegenerative disease is of key economic and societal importance in view of our increasingly ageing population and the burden posed from the prevalence of these diseases. The project seeks to make advances in basic science, through the development of new hydrogel materials and study of their role as synthetic ECM. At the same, the application of these materials to generate 3D neural tissues has significant translational potential.

Synergies from the project include access to highly customisable, chemically defined synthetic ECMs that have already been demonstrated to have potential in 3D cultures. In turn, the commercial partner benefits from applying these materials in cutting edge technologies with significant potential for clinical translation, demonstrating the value of their products. Iterative development will mean that findings from the academic partner will be fed back to the commercial partner to continually improve the hydrogel materials.

Apply using course: DPhil in Chemistry

MRC INDUSTRIAL CASE STUDENTSHIPS 2025

Designed to nurture the academic entrepreneurs of the future, the Enterprise studentship programme offers a stimulating educational experience as part of the Oxford-MRC DTP cohort, with the additional benefit of working closely with an industrial partner. This will provide entrepreneurial training opportunities and an insight into how commercial science is conducted alongside a superb academic base within the University. Students will work for at least 3 months in the associated company.

ELIGIBILITY

They are open to both UK and non-UK nationals and will follow the UKRI student eligibility requirements. UKRI will normally limit the proportion of international students appointed each year through individual training grants to 30% of the total intake each year.

FUNDING PACKAGE

Each iCASE studentship is fully-funded – it includes four years of stipend at the UKRI stipend level + £2,500 p.a., course fees, and a generous research training support grant.

APPLICATIONS DEADLINE

Applications must be received by 12 noon (UK time) Tuesday 3 December 2024. Details on entry requirements and how to apply can be found below.

For details of entry requirements please go to the Oxford-MRC DTP iCASE 2025 Projects page.

HOW TO APPLY

Before applying for this project we recommend you contact the lead supervisors for informal discussion.

To make a formal application, please complete the University’s online application form for the DPhil course specified under the project description above. Please indicate the iCASE project clearly by inserting ‘iCASE’ before the project title and by using the reference code iCASE. You will need to provide a personal statement (500 words max if applying for a project hosted by one of Medical Sciences departments – please note that this limit might be different if a project is hosted by one of MPLS departments in which case follow their requirement) detailing your interest and fit for the studentship. Note that no project proposal is required for the iCASE studentship applications.

If you wish to apply for a combination of iCASE and other projects within the hosting department, this can be done on the same application form (max number of projects you can apply for on one application depends on the department you wish to apply to). If you wish to apply for iCASE projects within different departments, you will have to make separate applications directly through those departments.

If you have any queries about the iCASE application process (questions about the project should be directed to the lead supervisor), please email mrc@medsci.ox.ac.uk.