Descrizione del progetto
Ricerca sugli organoidi di retina
La necessità di biomarcatori non invasivi per la malattia di Alzheimer (AD) è urgente. La retina condivide un’origine embriologica con il cervello e potrebbe fungere da strumento diagnostico riflettendo la patologia caratteristica dell’AD. Fino ad ora, le difficoltà a livello tecnologico hanno impedito la creazione di un modello biofisico con gli organoidi di retina. Il progetto ROMB, finanziato dall’UE, si propone di sviluppare un modello biofisico per la retina come modello in vitro dell’AD. Il modello sarà realizzato utilizzando organoidi di retina come modello fisiologico in vitro e consentirà misurazioni meccaniche dei tessuti e letture dell’attività neuronale. I ricercatori propongono di modellare l’AD utilizzando organoidi murini di retina con una mutazione del gene APP per studiare le aggregazioni peptidiche che sono la caratteristica dell’insorgenza della malattia.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- medical and health sciencesclinical medicineophthalmologyglaucoma
- natural sciencesbiological sciencesbiochemistrybiomolecules
- medical and health sciencesmedical biotechnologycells technologiesstem cells
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
80539 MUNCHEN
Germania