Descripción del proyecto
Órgano en una chip para la esquizofrenia
El óxido nítrico (NO) es una molécula de señalización que interviene en diversos procesos fisiológicos, como la regulación del flujo sanguíneo y las respuestas inmunitarias. Sin embargo, una producción desregulada de NO puede conducir a un estrés nitrosativo que cause daños en los componentes celulares. Esto también puede provocar la alteración de la barrera hematoencefálica que regula el paso de sustancias entre el torrente sanguíneo y el encéfalo. El equipo del proyecto CHIPzophrenia, financiado por el Consejo Europeo de Investigación, pretende desarrollar una novedosa tecnología de órgano en un chip para investigar la repercusión de los factores estresantes nitrosativos en las interacciones multicelulares de la barrera hematoencefálica, especialmente en relación con la esquizofrenia. La tecnología permite controlar el entorno bioquímico para realizar estudios biomoleculares reproducibles y se espera que aporte información nueva sobre los mecanismos biológicos de la esquizofrenia.
Objetivo
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.
Ámbito científico
- 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
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
100 44 Stockholm
Suecia