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.