Opis projektu
„Narząd na chipie” w leczeniu schizofrenii
Tlenek azotu (NO) jest cząsteczką sygnałową zaangażowaną w różne procesy fizjologiczne, w tym regulację przepływu krwi i odpowiedzi immunologiczne. Jednak rozregulowana produkcja NO może prowadzić do stresu nitrozacyjnego, który powoduje uszkodzenie struktur komórkowych. Może to również prowadzić do zakłócenia bariery krew-mózg, która reguluje przepływ substancji między krwiobiegiem a mózgiem. Finansowany przez Europejską Radę ds. Badań Naukowych projekt CHIPzophrenia ma na celu opracowanie nowej technologii typu „narząd na chipie” w celu zbadania wpływu stresorów nitrozacyjnych na wielokomórkowe interakcje bariery krew-mózg, szczególnie w odniesieniu do schizofrenii. Technologia ta umożliwia kontrolę nad środowiskiem biochemicznym w celu prowadzenia powtarzalnych badań biomolekularnych i ma rzucić światło na biologiczne mechanizmy schizofrenii.
Cel
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.
Dziedzina nauki
- 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
Słowa kluczowe
Program(-y)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Temat(-y)
System finansowania
HORIZON-ERC - HORIZON ERC GrantsInstytucja przyjmująca
100 44 Stockholm
Szwecja