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Feedback-control of the Microenvironment: Modular Organ-on-Chip Technology to elucidate the role of Neurovascular Stress in Schizophrenia

Project description

Organ-on-chip for schizophrenia

Nitric oxide (NO) is a signaling molecule involved in various physiological processes, including the regulation of blood flow and immune responses. However, dysregulated production of NO can lead to nitrosative stress causing damage to cellular components. This can also lead to disruption of the blood brain barrier that regulates passage of substances between the bloodstream and the brain. Funded by the European Research Council, the CHIPzophrenia project aims to develop a novel organ-on-chip technology to investigate the impact of nitrosative stressors on the blood-brain barrier's multicellular interactions, particularly in relation to schizophrenia. The technology allows control over the biochemical environment for reproducible biomolecular studies and is expected to shed light into the biological mechanisms of schizophrenia.


A well-controlled microenvironment is paramount for reproducible biomolecular studies. Organs-on-chips are in-vitro cell culture systems that employ microfluidic and biomaterial engineering towards that goal. They combine the advantages of animal models (physiological environment) with those of plastic-dish culture (human cells), and thereby hold exceptional promise in unraveling the biological processes that underlie health and disease. Yet control over the biochemical environment remains poor.
With CHIPzophrenia, I propose to develop a new generation of organ-chip, one that features feedback-enabled control of the biochemical environment. I aim to realize dynamic and well-controlled application of stable therapeutics (via feedback sensors and flow control), and crucially also of highly volatile oxygen/nitrogen stressors by relying on electrochemistry to generate them in situ. My goal is to moreover implement a highly functional modular architecture so that the system can easily be repurposed and sensor/control modules reused – all with negligible dead volumes and displacement (key challenges in current organ-chips towards novel functionalities).
I intend to leverage this organ-chip to elucidate how nitrosative stressors disrupt the complex multicellular interactions of the blood-brain barrier, where existing in-vitro models fail to provide the requisite cellular and chemical microenvironment. Yet such disruption is implicated in a wide array of disorders – including schizophrenia, where our biological understanding remains poor and in-vivo models are uniquely challenging. I will specifically test the hypothesis that nitrosative dysregulation of perivascular cells plays a causative role in neuronal dysfunction associated with the disorder. Not only will CHIPzophrenia thus reveal new potential treatment targets, but it will also establish the platform as a transformative tool for dynamic and well-controlled in-vitro research into stress-related disorders and beyond.

Host institution

Net EU contribution
€ 1 499 375,00
100 44 Stockholm

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Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
Total cost
€ 1 499 375,00

Beneficiaries (1)