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

Projektinformationen

ORCHESTRATE

ID Finanzhilfevereinbarung: 694801

DOI

10.3030/694801

Projekt abgeschlossen

EK-Unterschriftsdatum 23 September 2016

Startdatum 1 Oktober 2016

Enddatum 30 September 2020

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 2 655 000,00

EU-Beitrag

€ 2 655 000,00

Koordiniert durch

UNIVERSITEIT MAASTRICHT
Netherlands

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

Berichtszeitraum: 2019-10-01 bis 2020-09-30

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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