Project Multimodal analysis of CRB1 related retinal degeneration in human iPSC derived organoids

Basic data

Title:
Multimodal analysis of CRB1 related retinal degeneration in human iPSC derived organoids
Duration:
01/02/2019 to 31/01/2022
Abstract / short description:
Mainly based on long-term cultivated retinal organoids derived from hiPSCs, this project aims at generating knowledge and providing candidate targets for interventional cell based as well as molecular therapy of patients suffering from CRB1 associated retinal degeneration. In the search for understanding the pathomechanisms and the underlying mechanisms of the varying clinical manifestations of this form of retinal degeneration, we will develop tools that allow assessment of molecular defects caused by CRB1 mutations. For that, we have and will further generate control and patient specific iPSCs and generate retinal organoids thereof carrying homozygous mutations in the CRB1 gene. In a multimodal analysis, we will investigate patient specific deregulations of global gene expression and changes in protein expression and protein interactions dependent on CRB1. This will be complemented by histological and high-resolution microscopy imaging techniques (2 -Photon, STED und EM) to analyse topological (immunohistochemistry) and micro-anatomical features dependent on CRB1. Given that we and others see different degrees of disease severity in patients homozygous for the same CRB1 mutation, we will comparably analyse organoids derived of patients with different disease severity to look for disease modifiers as well as mechanisms for protection. This requires a holistic view on the role of CRB1 within retinal development, which we will attempt to gain by combining a deep multi-omics approach in combination with advanced bioinformatics and computational modelling. Based on a deeper understanding on the role of CRB1 in cellular signalling pathways we aim to obtain insights into possible endogenous protective mechanisms associated with CRB1 retinal degeneration, which can serve as a future basis for therapy development.
Keywords:
iPSC-derived retinal organoids
multi-omics analysis
CRB1

Staff

Managers

Center for Ophthalmology
Hospitals and clinical institutes, Faculty of Medicine

Contact persons

Faculty of Medicine
University of Tübingen

Local organizational units

Research Center for Ophthalmology
Center for Ophthalmology
Hospitals and clinical institutes, Faculty of Medicine

Funders

Bonn, Nordrhein-Westfalen, Germany
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