How the 3D-BrAIn project started
Introducing Femke de Vrij, Principal Investigator and Project Leader 3D-BrAIn
In today’s world, researchers can grow brain cells in a dish by “simply” reprogramming cells that can be taken from a patient’s skin or blood cells, using so-called “human induced pluripotent stem cell” (hiPSC) technology. With this technology, patient-derived hiPSCs can be turned into “brain organoids”, which are 3D neural networks that resemble the early developmental stage of the human frontal cortex. In other words, they are miniature and simpler versions of a part of the brain, that can serve as a tool to study brain development, diseases and potential treatments. Aiming to take this technology one step further, Femke de Vrij has received €2 million under the EIC Pathfinder Open call, to lead the 3D-BrAIn project – a European research project looking to revolutionize personalized precision medicine for central nervous system (CNS) disorders.
Femke de Vrij is principal investigator at the department of Psychiatry at Erasmus MC, leading a lab working on human disease models of neuropsychiatric disorders. “As a neurobiologist, I have always been fascinated by the brain since my master Medical Biology at Utrecht University, focused on neurobiology. I continued my focus as a PhD student at the Netherlands Institute for Neuroscience in Amsterdam, where I studied the molecular biology of Alzheimer’s disease,” Femke explains. After a postdoc period, she transitioned to the Psychiatry department at Erasmus MC in Rotterdam, where she now leads her own lab.
“The 3D-BrAIn project is truly multidisciplinary, as we need a perfect combination of brain organoid technology and neurobiological expertise, together with advanced MEA chip technology and next level data analysis solutions.”
The 3D-BrAIn project stemmed from a shared ambition between Femke, Steven Kushner and Alessandro Maccione of the Genova-based 3Brain company. Their goal was to bring together a team capable of performing custom-made high-density microelectrode array (MEA) recordings on an innovative brain organoid model. In other words, a group that has the expertise to integrate an advanced brain organoid model with an innovative platform for very high-density and accurate readings of the organoid’s neural network activity.
With 3Brain as a leader in microelectrode development, the consortium expanded to include renowned experts, such as neurobiologist Silvia Cappello from LMU Munich, as well numerical analysis experts Michele Piana and Cristina Campi from the University of Genova. In Femke’s own words: “The project is truly multidisciplinary, as we need a perfect combination of brain organoid technology and neurobiological expertise, together with advanced MEA chip technology and next level data analysis solutions.”
“In five years, we expect to successfully conclude the project by providing a proof-of-principle for the 3D-BrAIn central nervous system model.”
In the 3D-BrAIn project, a team of scientists, engineers and mathematicians is working together to create a microelectrode interface that can record the electrical signals from brain organoids at a very high resolution. Ultimately, this technology can be used to help improve the diagnosis and test new treatments for a range of neuropsychiatric and brain diseases, such as epilepsy or schizophrenia. Femke explains: “In five years, we expect to successfully conclude the project by providing a proof-of-principle for the 3D-BrAIn central nervous system model. By integrating brain organoids with 3D high-resolution MEA technology and advanced data collection using machine learning-based data processing, our ultimate goal is to create a platform for predictive and personalized modelling of brain diseases and therapeutic strategies.”
To accomplish this, there are of course challenges ahead. “Our main challenge will be the integration of the organoids with the 3D electrodes, considering that the timing of organoid development takes months. However, with our combined expertise in the consortium, we are well equipped to tackle this challenge. We aim to provide proof-of-principle by subjecting organoids from patients with defined neurodevelopmental disorders on the platform.”
In Femke’s lab, the team specializes in human iPSC-derived brain models of neuropsychiatric and neurodevelopmental disorders. “No surprise that a day in the lab will be spent for a large part in our dedicated cell culture labs, where the organoids are carefully nurtured for months. You will also find people working in our molecular lab on gene editing (modifying genes within cells) or immunostainings (a technique that helps visualize specific proteins within cells). Some are working in the dark behind our advanced confocal microscope, and others are working in our electrophysiology lab for whole cell patch clamp experiments or multielectrode array recordings of electrical signals from patient-derived neural networks and organoids.” Working closely with the other partners, Femke’s lab is responsible to integrate the organoids with the customized MEA chips from 3Brain, to achieve machine-learning based analysis of the resulting data of the brain organoids’ activity.
“Apart from the exciting scientific content, the 3D-BrAIn consortium is also really a pleasure to work with, combining the expertise from very knowledgeable and wonderful people in a pleasant collaboration.”
For Femke, the exciting prospect of the 3D-BrAIn project is to be able to record signals from their brain organoids at a very high resolution – something ground-breaking in the field. “This will allow us to get much better spatial information of the neural network activity. But apart from the exciting scientific content, the 3D-BrAIn consortium is really a pleasure to work with, combining the expertise from very knowledgeable and wonderful people in a very pleasant collaboration. What is key to success is that all the partners genuinely see the synergistic potential of this project and are dedicated to make it work. I’m very excited about the results to come!”
The 3D-BrAIn project kicked off in April 2023 and the team met for the first time in May at Erasmus MC to discuss for their 5-year journey ahead. Stay tuned and make sure to follow us to see the progress of the project!
