Title: A look at organoids in vision research: challenges and opportunities
The talk is online, please contact thomas.wheeler-schilling@ to receive Zoom login details. uni-tuebingen.de
Abstract: Recent advances in reprogramming and stem cell differentiation have revolutionised the study of genetic diseases. 3D retinal organoids recapitulate many of the features of the neural retina and enable us to study the potential mechanisms that underlie inherited retinal dystrophies. These model systems are ideally suited to study human genomic changes in the correct cellular context. Furthermore, they can be used to test potential therapies including, pharmacological treatments, antisense oligonucleotides and gene augmentation. Nevertheless, they have limitations that need to be carefully considered when designing experiments and interpreting data. I will discuss some examples of our recent retinal organoid research to illustrate their power and some of the challenges.
Professor Mike Cheetham research has focused on the cell biology of protein folding and the cellular machinery that facilitates protein folding, quality control and traffic. Early in his career, he identified the first human homologue of the bacterial chaperone protein DnaJ, showning that this protein can reduce the aggregation of a wide range of neurodegeneration associated proteins in vitro, in cells and in vivo. His team discovered that rhodopsin retinitis pigmentosa is similar to many other forms of neurodegeneration with imbalanced proteostasis, and identified that chaperones that play a role in rhodopsin biogenesis, as well as identifying small molecules that can promote rhodopsin folding. They have worked on the mechanisms of inherited retinal degeneration, and in particular ciliopathies that affect photoreceptor function. His lab uses a combination of model systems, including stem cell models, to probe disease mechanisms and has pioneered the use of 3D retinal organoids to model genetic disease. They recently used this technology to help develop an antisense therapy for the ciliopathy LCA10, with the Netherlands company ProQR, which is now in phase 3 clinical trial.