Engineering a scalable platform for organoid-based drug screens

Organoids are an essential tool for studying development due to their ability to reproduce specific developmental stages in vitro,and are promising for disease modeling since they can be generated from patient-derived stem cells. While the first generation of organoids were highly variable in terms of cell types and spatial architecture, the research community has in the recent years put particular emphasis on increasing organoid reproducibility. However, organoids often remain structurally variable and are therefore difficult to use for analysing subtle, early disease phenotypes in patient cells. Also, organoids often lack scalability, making them difficult to use in high-throughput applications such as screens. To overcome these challenges, we have previously shown that hundreds of engineered neural organoids can be grown on micropatterns in parallel with unprecedented reproducibility, allowing for the detection of subtle phenotypes of Huntington’s disease using a combination of single-cell sequencing and imaging techniques. We have used this platform to develop an organoid-based drug-screening platform with associated analysis methods based on deep neural networks. The Metzger lab continues to develop both reproducible organoid systems and corresponding quantitative analysis methods for use in different drug and genetic screening paradigms, with the aim of rapidly developing patient-specific, personalized treatments.