Intra-CREATE Engineering and Health. Selected project: CALIPSO
CNRS@CREATE is pleased to announce, as host institution, the selection of the project “CALIPSO: Computer Assisted Live Imaging for Predictive Screening of Organoids“ as part of the INTRA-CREATE call for projects on “Intersection of Engineering and Health”.
PIs and partners
|Lead PI (1)||Jean-Baptiste Sibarita||CNRS@CREATE|
|Lead PI (2)||Virgile Viasnoff||NUS|
|Co-I (1)||Veronique Angeli||SHARE|
|Co-I (2)||Peter Török||NTU|
|Co-I (3)||Pierre Francois Lenne||CNRS@CREATE|
|Co-I(4)||Alfonso Martines-Arias||Cambridge university|
Jean-Baptiste Sibarita, Lead PI (1)
Virgile Viasnoff, Lead PI (2)
Organoids, in vitro 3D cell culture mimicking organ organization, offer immense potential in regenerative medicine and drug testing. They rely on the in vitro culture of stem cells that differentiate into specific lineages in a determined time sequence. In response to exogenously provided signals and culture conditions, the cells form aggregates and self-organize into structures that share strong morphological and functional similarities with real organ organization. A growing number of such organotypic cultures are being developed, mimicking for example the intestine, the retina, the kidney or the pancreas. The rapid maturation of this groundbreaking technology provides invaluable models to study human biology and development outside of the human body, overcoming ethical issues. Organoids have enormous potential both scientifically and economically since they potentially constitute powerful in vitro models for fundamental developmental research, toxicology studies, drug discovery and predictive or regenerative medicine. However, this approach faces the challenge to engineer cell lines and appropriate culture conditions to obtain mature organoids that adequately phenocopy physiological response or organ functions. This essential issue in cell manufacturing is compounded by the absence of quantitative high throughput solutions to assess the organoid development states. Indeed, existing quality control techniques, i.e. genomics or imaging, are low throughout and destructive.
In this three-year project, we will develop a new generation of high content screening platform for simultaneous 3D live imaging of more than 1,000 organoids. It will rely on our published and patented single objective SPIM technique, which we will extend to screen the cellular movements of developing gastruloids and liver organoids together with their differentiation state and extracellular matrix spatial distribution. The data obtained will be analyzed using machine learning to provide new quantitative statistical analysis tools characterizing the diversity of morphogenetic movements within each organoid. Using correlative clustering, we will then demonstrate how such quantification can lead to individual organoid outcome prediction in a non-destructive way.
- An automated stand-alone screening platform for prolonged (>3 days) 3D live imaging of organoids. It will comprise the hardware, the acquisition and database software as well as the dedicated chips comprising of 10,000 micro-compartments.
- A database containing time-lapse recordings of the morphodynamics movements (up to 100 time points), the final genomic state and the rheological properties of >5,000 gastruloids and liver organoids originating from at least 10 different stem cell sources and culture conditions.
- A dedicated optimized workflow for AI-based quantitative analysis of the morphodynamics patterns and matrix deposition in organoids.
- An AI-based clustering software for predicting the final organoid state from its live morphodynamics properties
We expect this platform to be later exploited in drug testing and regenerative medicine.