Descrizione del progetto
Organi su chip per la schizofrenia
L’ossido nitrico (NO) è una molecola di segnalazione coinvolta nello svolgimento di vari processi fisiologici, tra cui la regolazione del flusso sanguigno e le risposte immunitarie. Una sua produzione disregolata può comportare stress nitrosativo provocando danni ai componenti cellulari, che a loro volta possono determinare l’interruzione della barriera ematoencefalica responsabile di regolare il passaggio di sostanze tra il flusso sanguigno e il cervello. Finanziato dal Consiglio europeo della ricerca, il progetto CHIPzophrenia si propone di sviluppare una nuova tecnologia di tipo «organo su chip» per studiare l’impatto dei fattori di stress nitrosativo sulle interazioni multicellulari della barriera ematoencefalica, in particolare in relazione alla schizofrenia. La tecnologia del progetto permetterà di controllare l’ambiente biochimico per effettuare studi biomolecolari riproducibili e, secondo le previsioni, farà luce sui meccanismi biologici alla base della schizofrenia.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
100 44 Stockholm
Svezia