Tracking the Dynamics of Human Metabolism using Spectroscopy-Integrated Liver-on-Chip Microdevices

Informations projet

OCLD

N° de convention de subvention: 681870

DOI

10.3030/681870

Projet clôturé

Date de signature de la CE 7 Juillet 2016

Date de début 1 Octobre 2016

Date de fin 30 Septembre 2021

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 2 118 175,00

Contribution de l’UE

€ 2 118 175,00

Coordonné par

THE HEBREW UNIVERSITY OF JERUSALEM
Israel

Periodic Reporting for period 4 - OCLD (Tracking the Dynamics of Human Metabolism using Spectroscopy-Integrated Liver-on-Chip Microdevices)

Période du rapport: 2021-04-01 au 2021-09-30

Résumé du contexte et des objectifs généraux du projet

The natural cycle of day and night on our planet introduces inherent cycles to our local environment. These cyclical differences in light, temperature and food availability produce hormonal oscillations in higher organisms that allow us to better prepare for morning activity as well as prolonged fasting during the night. Disruption of these circadian rhythms leads to metabolic syndrome, obesity and type-2 diabetes. These metabolic diseases are pronounced in nightshift workers and are exacerbated by widespread light pollution. While current work on circadian rhythms focuses on animal models, differences in metabolism, physiology and genetics make it difficult to translate these findings to clinical results. In this project we sought to develop a three-dimensional models of human organs that maintain natural metabolic rhythms in a micro fluidic environment that mimic human physiology.

Our model successfully captured metabolic oscillations in a 3D model of the human liver, as well as the onset of circadian rhythms in a 3D model of a developing embryo. This proprietary technology was patented at the Hebrew University of Jerusalem and licensed to Tissue Dynamics, a groundbreaking Organ-on-Chip company developing the first physiological bioanalyzer. The last 18 months of the project included major breakthroughs identifying novel metabolic mechanisms of drug induced kidney and cardiac injury as well as identified virus-induced lipotoxicity as a cause of lung damage in COVID-19.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

We integrated in line metabolic sensors in our liver on chip microdevice, enabling a real time analysis of metabolic fluxes. This work was published with L’Oreal (Paris, France) on the cover of Lab Chip, 2019. We developed an automated flow control unit together with Fluigent (Paris,France) capable of oscillating hormones and temperature in organ on chip microdevices. This technology was submitted as a patent application and licensed to Tissue Dynamics Ltd.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

We have published several high impact papers and submitted a patent application. Several other projects on kidney and heart on a chip are ongoing.

Human micro-liver showing metabolic zonation on chip