05 Mar 2025
Creating brain circuits with human neurons and fluid walls
Oxford biologists and engineers awarded £2 million from BBSRC to grow human neurons as brain circuits in chambers made of oil
Microfluidics with fluid walls is a new and flexible technology for studying neuronal circuits in-vitro using hiPSCs. Human iPSCs are differentiated into different neuron types and fluid walls are used to create microenvironment that mimic in-vivo conditions.
The circuits of the brain linking together the regions known as the midbrain, the striatum and the cortex are critical to understanding disorders such as Parkinson’s disease, addiction and autism. Understanding and modelling how the circuit works in human neurons has been difficult, mainly due to the inaccessibility of the human brain and the limitations of current technologies to reliably grow circuits of human neurons in the laboratory.
To tackle this challenge, a new Oxford collaborative team of biologists and engineers led by Associate Professor of Engineering Ed Walsh, Professor Richard Wade-Martins (Department of Physiology, Anatomy & Genetics (DPAG)/Kavli), and Dr Ricardo Marquez Gomez (DPAG/Kavli) has been awarded a grant of £2 million from the BBSRC to bring together the technologies of human stem cells and oil-wall microfluidics.
The human stem cells will be used to generate each specific neuronal subtype of the cortical-striatal-midbrain circuit held within oil-walled chambers. Such chambers can reliably construct microenvironments and circuits with long-term accessibility, contrasting with current microfluidic technologies based on rigid and single use plastics.
The project will study the physiology, regulation and cellular architecture of neurons in the circuit. Taking advantage of the adaptability properties of the fluid-walls technology, the team will also explore the regulation of gene expression in the cell body and along the neuronal axons which form the circuits to understand how genes control neuronal circuit function.
Early work from the team published in 2024 illustrated how the three neuron types could be grown together to help study Parkinson’s disease (Do et al NPJ Parkinson’s 2024), and that the oil-walls system supports neuronal growth (Nebuloni, Do et al Lab on a Chip 2024). The new BBSRC project kicked off in January 2025 for five years.
