Description du projet
Un organe sur puce pour soigner la schizophrénie
L’oxyde nitrique (NO) est une molécule de signalisation impliquée dans divers processus physiologiques, notamment la régulation du flux sanguin et les réponses immunitaires. Cependant, une production dérégulée de NO peut conduire à un stress nitrosatif causant des dommages aux composants cellulaires. Cela peut également entraîner une perturbation de la barrière hématoencéphalique qui régule le passage des substances entre la circulation sanguine et le cerveau. Financé par le Conseil européen de la recherche, le projet CHIPzophrenia vise à développer une nouvelle technologie d’organe sur puce pour étudier l’impact des facteurs de stress nitrosatifs sur les interactions multicellulaires de la barrière hémato-encéphalique, en particulier en relation avec la schizophrénie. Cette technologie permet de contrôler l’environnement biochimique pour des études biomoléculaires reproductibles et devrait permettre de mieux comprendre les mécanismes biologiques de la schizophrénie.
Objectif
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.
Champ scientifique
- natural sciencesphysical sciencesclassical mechanicsfluid mechanicsmicrofluidics
- natural scienceschemical scienceselectrochemistry
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensors
- medical and health sciencesclinical medicinepsychiatryschizophrenia
- engineering and technologyother engineering and technologiesmicrotechnologyorgan on a chip
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
100 44 Stockholm
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