Projektbeschreibung
Erforschung von Netzhautorganoiden
Es werden dringend nichtinvasive Biomarker für die Alzheimer-Krankheit gebraucht. Die Netzhaut hat einen gemeinsamen embryologischen Ursprung mit dem Gehirn und kann als diagnostisches Instrument dienen, das die pathologischen Kennzeichen der Alzheimer-Krankheit widerspiegelt. Bislang standen der Etablierung des Netzhautorganoids als biophysikalisches Modell technische Schwierigkeiten im Wege. Das EU-finanzierte Projekt ROMB verfolgt nun das Ziel, ein biophysikalisches Modell der Netzhaut zum In-vitro-Modell der Alzheimer-Krankheit weiterzuentwickeln. Das Modell soll unter Einsatz von Netzhautorganoiden als physiologisches In-vitro-Modell aufgebaut werden und wird gewebemechanische Messungen und Aufzeichnungen der neuronalen Aktivität ermöglichen. Die Forschungsgruppe schlägt die Modellierung der Alzheimer-Krankheit unter Einsatz von Netzhautorganoiden der Maus mit einer Mutation im APP-Gen vor, um jene Peptidaggregate zu untersuchen, die den Krankheitsausbruch kennzeichnen.
Ziel
The retina carries signatures of neuronal diseases which have been linked to mechanical abnormalities,
including Glaucoma and Alzheimer’s disease. Yet no biophysical retina model exists due to a cross-disciplinary
challenge: While stem cell derived organoids mimic the retina in vitro, organoid research has been
limited by large variations in cell and tissue organization. Mechanobiology, in turn, has revealed mechanical
signals as essential players in regulating cellular behavior to guide organogenesis. Accordingly, the ball is in
the court of physicists and bioengineers to quantify those mechanical signals and shape tissue growth by
tailoring the physical interactions of cells with their environment. Finally, the functionality of the retina has to
be quantified via neuroscience techniques. This multifaceted challenge has prevented the establishment of the
retina organoid as a biophysical model.
ROMB introduces a biophysical model for the retina which I will use to model Alzheimer’s disease in vitro.
It will be built on 4 cross-disciplinary posts: (i) retina organoids as a physiological in vitro model, (ii) tissue
mechanics measurements, (iii) neuronal activity readout and (iv) disease modeling. First, I will reveal the
mechanical building plan of retina organoids using ferrofluid droplets as mechanical actuators, hereby opening
the field of organoid mechanobiology. In a second step, the organoid’s 3D neuronal function will be recorded
using lightsheet microscopy. Mechanical, functional and genetic access will allow me in a final step to detect
and manipulate Alzheimer’s disease: using mouse retina organoids with a mutation in the App gene, I will
mechanically characterize the formation of those peptide aggregates which are the hallmark of disease onset.
ROMB opens the door to engineering functional retinas in vitro. Moreover, it will be uniquely suited to tackle
mechanically related neuronal diseases and promises a breakthrough for basic and applied research.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- medical and health sciencesclinical medicineophthalmologyglaucoma
- natural sciencesbiological sciencesbiochemistrybiomolecules
- medical and health sciencesmedical biotechnologycells technologiesstem cells
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-STG - Starting GrantGastgebende Einrichtung
80539 MUNCHEN
Deutschland