Projektbeschreibung
Organchip für Schizophrenie
Stickstoffmonoxid ist ein Signalmolekül, das an verschiedenen physiologischen Prozessen beteiligt ist, u. a. an der Regulierung des Blutflusses und an Immunreaktionen. Eine dysregulierte Stickstoffmonoxid-Produktion kann jedoch zu nitrosativem Stress führen, der Zellbestandteile schädigt. Dies kann auch zu einer Störung der Blut-Hirn-Schranke führen, die die Passage von Substanzen zwischen dem Blutkreislauf und dem Gehirn regelt. Das vom Europäischen Forschungsrat finanzierte Projekt CHIPzophrenia zielt darauf ab, eine neuartige Organchip-Technologie zu entwickeln, um die Auswirkungen nitrosativer Stressoren auf die multizellulären Interaktionen der Blut-Hirn-Schranke zu untersuchen, insbesondere im Zusammenhang mit Schizophrenie. Die Technologie ermöglicht die Kontrolle über die biochemische Umgebung für reproduzierbare biomolekulare Untersuchungen und wird voraussichtlich Aufschluss über die biologischen Mechanismen der Schizophrenie geben.
Ziel
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.
Wissenschaftliches Gebiet
- 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
Schlüsselbegriffe
Programm/Programme
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thema/Themen
Finanzierungsplan
HORIZON-ERC - HORIZON ERC GrantsGastgebende Einrichtung
100 44 Stockholm
Schweden