Building complex life through self-organization: from organ to organism

Información del proyecto

ORCHESTRATE

Identificador del acuerdo de subvención: 694801

DOI

10.3030/694801

Proyecto cerrado

Fecha de la firma de la CE 23 Septiembre 2016

Fecha de inicio 1 Octubre 2016

Fecha de finalización 30 Septiembre 2020

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 2 655 000,00

Aportación de la UE

€ 2 655 000,00

Coordinado por

UNIVERSITEIT MAASTRICHT
Netherlands

Periodic Reporting for period 3 - ORCHESTRATE (Building complex life through self-organization: from organ to organism)

Período documentado: 2019-10-01 hasta 2020-09-30

Resumen del contexto y de los objetivos generales del proyecto

A major challenge in regenerative medicine is to create phenotypic functioning tissues by controlling cell behaviour. We particularly lack the ability to form complex tissues composed of multiple cell types and with three-dimensional architecture, which are defining features of most tissues. We know that cells are conferred with the ability to choreograph their own development through self-organization. I hypothesize that if we actively promote this intrinsic capacity with new cell culture platforms, we can orchestrate self-organization to make complex tissues, organs, and even organisms with a high degree of reproducibility and in large numbers.

Society stands to benefit greatly from regenerative medicine, which is a multidisciplinary field that combines biology, engineering and medicine to replace or regenerate organs and tissues. In particular, those suffering from chronic diseases may be presented with a cure for their condition in the form of a new organ or tissue. In ORCHESTRATE, we are developing technology and know-how to advance this field.

This proposal begins with the design and development of new cell culture platforms. Building upon our proprietary fabrication and microfluidic technology, we will create advanced platforms that will control how cells aggregate and enable the application of biomolecules with spatial and temporal resolution to orchestrate self-organization. This technology will be transferred into three projects focussing on different organs or organisms. For each, we need to find the right conditions to enrich for desired phenotypes and functions, which means that we need quantitative read-outs in the form of single cell information and imaging technology.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

In this project, we built multiple versions of cell culture platforms based on microfluidics. These allow us to both study and control cell behaviour at the same time. The platforms contain channels to control the exposure of cells to biomolecules with both spatial and temporal control. We put significant effort into establishing an image acquisition platform for microscopic analyses of three-dimensional cell aggregates. We can image large quantities of aggregates in a partly automated manner. We developed an in vitro model of the adult pancreatic islet in which we investigated the influence of three cell types (alpha-, beta- and endothelial cells) on organization and function. And we established greater complexity in the model of a mouse blastocyst. These results have been disseminated in scientific posters and publications, and (especially for the work related to the mouse blastocyst) to the public.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

The outcomes beyond the start of the art of this project are three-fold: first, we developed a new generation of cell culture platforms with integrated microfluidics; second, we uncovered new knowledge about how to orchestrate self-organization; and third, we made in vitro models of pancreatic islets and mouse blastocysts.

ORCHESTRATE is about directing the self-organization of complex cellular structures