Description du projet
Une recherche sur les organoïdes de la rétine
Il y a un besoin urgent en biomarqueurs non invasifs de la maladie d’Alzheimer (MA). La rétine partage une origine embryonnaire avec le cerveau et peut servir d’outil diagnostique qui reflète le trait distinctif de la MA. Jusqu’à présent, les défis technologiques n’ont pas permis d’établir l’organoïde de la rétine comme modèle biophysique. Le projet ROMB, financé par l’UE, entend développer un modèle biophysique pour la rétine comme modèle in vitro de la MA. Ce modèle sera établi en utilisant des organoïdes de la rétine comme modèle physiologique in vitro et permettra de prendre des mesures tissulaires mécaniques et de lire l’activité neuronale. Les chercheurs proposent de modéliser la MA en utilisant les organoïdes de rétines de souris avec une mutation du gène APP pour étudier les agrégats de peptides qui sont le signe distinctif de l’apparition de la maladie.
Objectif
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.
Champ scientifique
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- medical and health sciencesclinical medicineophthalmologyglaucoma
- natural sciencesbiological sciencesbiochemistrybiomolecules
- medical and health sciencesmedical biotechnologycells technologiesstem cells
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
80539 MUNCHEN
Allemagne