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Engineering 3D brain circuits for modelling neurodegenerative diseases

Contribute to Materials & Devices for Life Sciences at EIT, redefining nanopore technologies and progressing new approaches in tissue engineering, as a Graduate Ellison Scholar.

Key facts

Project description

Brain circuits are complex, interconnected networks of neural cells that process specific types of information and drive behaviour. Neurodegenerative diseases result in the progressive degradation and malfunction of specific neuronal networks. The main neuronal circuitry affected in Parkinson’s disease (PD) is established by cortical, striatal and dopamine neurons. However, most research exploring this circuitry in health and disease has taken place in animal models, making the translatability of PD animal research into humans contentious.

Recent progress has reported simplified circuits, such as assembloids, made from human stem cells and their derived organoids. However, further efforts to produce physiologically relevant circuit models are required to better resemble aspects of neurodegenerative diseases. Notably, the reported brain circuits are missing a key component: glial cells. Glial cells comprise about half of the brain’s volume and actively wire and orchestrate neural circuits. These cells guide circuit assembly, control synaptic plasticity, modulate network activity and provide vital metabolic support.

To improve the current circuit model, we propose to add glial cells into our existing 3D printed neural circuits. By combining stem cell and tissue engineering technologies, we aim to produce more realistic brain circuits for modelling PD. The engineered circuits will be characterised using molecular biomarkers to confirm the specific cell types, their maturation, and synaptic connections. We will also evaluate circuit function using calcium imaging with calcium dyes and optogenetics, as well as electrophysiological recordings using multielectrode arrays.

The Tissue Engineering Group at the Materials and Devices for Life Sciences (MDLS), develops 3D tissues using patient-derived stem cells for disease modelling and implantation for repair. We have developed droplet 3D-printing and microfluidic techniques for the construction of defined and patterned 3D tissues. The Wade-Martins lab (Department of Physiology, Anatomy and Genetics, the University of Oxford) has led an effort to develop a 2D microfluidic system to co-culture cortical, striatal and dopamine neurons derived from human stem cells (hiPSCs). Our ongoing collaboration has established a method to generate 3D PD circuits using hiPSCs derived neurons. The proposed project will incorporate glial components, including astrocytes and microglial, and make improvements in the engineering technology to increase the functionality of the circuits.

We welcome candidates with biology, medicine, biophysics and bioengineering backgrounds. Experience in stem cell biology is desirable. DPhil students will work collaboratively in a multidisciplinary team engaged in cell biology, biophysics, biochemistry, and device and tissue engineering. 

Skills Required

  • Degree in biology, medicine, biochemistry, bio- or tissue engineering.
  • Cell and molecular biology
  • Stem cell and organoid culture
  • RNA sequencing or proteomics
  • Experience and interest in multidisciplinary research 

Skills to be Developed

  • Stem cell differentiation
  • 3D co-culture
  • 3D printing and microfluidics
  • 3D tissue imaging and characterisation techniques
  • Disease modelling 

Relevant Background Reading

  1. Zhou, L., Wolfes, A.C., Li, Y., Chen, D.C.W., Ko, H., Szele, F.G. and Bayley, H. Lipid bilayer supported 3D printing of human cerebral cortex cells reveals developmental interactions. Advanced Materials 32, e2002183 (2020). DOI: 10.1002/adma.202002183
  2. Jin, Y., Mikhailova, E., Lei, M., Cowley, S.A., Sun, T., Yang, X., Zhang, Y., Liu, K., Catarino, D., Soares, L.C. and Bandiera, S., 2022. Functional Integration of 3D-Printed Cerebral Cortical Tissue into a Brain Lesion. Nature Communications 14, 5968 (2023).  https://doi.org/10.1038/s41467-023-41356-w
  3. Do, Q.B., Noor, H., Marquez-Gomez, R. et al. Early deficits in an in vitro striatal microcircuit model carrying the Parkinson’s GBA-N370S mutation. npj Parkinsons Dis. 10, 82 (2024). https://doi.org/10.1038/s41531-024-00694-2 

How to apply

Stage 1: Apply to Ellison Institute of Technology

Submit an application to Ellison Institute of Technology (EIT) by 5pm UK time on Tuesday 1 December 2026.

We encourage you to apply early, as applications will be reviewed as they are received.

Learn more and apply

Stage 2: Apply to the University of Oxford 

If selected by EIT, you will receive conditional funding and will be invited to apply to the University of Oxford by following the instructions on the course page.

Your application will then follow the standard graduate admissions process and will be assessed against the entry requirements shown on the course page.