Skip to main content
Go to the home page of the European Commission (opens in new window)
English en
CORDIS - EU research results
CORDIS

Mechanisms of liver regeneration and disease across scales; from molecules to cells and tissue

Project description

Insight into the principles of liver regeneration

The liver has a remarkable capacity to regenerate, but the molecular and cellular mechanisms governing this process remain poorly understood. Importantly, its deregulation leads to conditions such as fibrosis and chronic liver disease. The ERC-funded REG_ORGatSCALE project investigates the principles of liver regeneration using a multidisciplinary approach. Researchers will identify gene regulatory networks driving regeneration and dissect how interactions between epithelial and mesenchymal cells control repair and disease. By creating complex multicellular organoids that reconstruct liver tissue architecture in a dish, they hope to transfer these findings to human tissues. Determining which regenerative principles are conserved across species will have broad implications for understanding and treating liver disease.

Objective

Despite recent advances, the principles that regulate liver regeneration and how their deregulation leads to disease remain largely unknown. The main goal of this application is to uncover molecular and cellular principles that govern liver regeneration and disease and exploit this knowledge to develop more complex multicellular organoid systems capable of reconstructing liver tissue in a dish. We will adopt a multi-scale (from molecule to tissue), and multidisciplinary approach, addressing the interplay between cell-intrinsic and cell-extrinsic mechanisms in damage paradigms that result in repair vs disease.

In Aim 1 we will identify the genomic loci (e.g. Transcription factors, signalling pathways or epigenetic regulators) involved in regeneration and disease, to gain a systems-level understanding of the gene regulatory mechanisms driving liver regeneration and disease.

In Aim 2 we will investigate the biochemical signals mediated through cell-cell interactions between ductal cells and mesenchymal, to gain mechanistic understanding on how epithelial – mesenchymal cellular interactions regulate regeneration and their role in disease, particularly fibrosis.

In Aim 3 we will build complex multicellular organoids to reconstruct the liver lobule cellular interactions and architecture.

An in-depth understanding of the molecular and cellular mechanisms driving tissue regeneration and their deregulation in disease holds the potential to uncover new principles of liver biology. The generation of complex multicellular organoids that recapitulate liver cellular interactions and architecture will provide valuable tools for future mechanistic studies aiming at investigating molecular and cellular principles of tissue maintenance, repair and disease. Transferring these to human tissues will facilitate future studies addressing the long-standing question as to which principles of repair are conserved in humans and which are human specific.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

See all projects funded under this funding scheme

Call for proposal

(opens in new window) ERC-2022-COG

See all projects funded under this call

Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution
€ 1 999 980,00
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany
Region
Berlin Berlin Berlin
Activity type
Research Organisations
Links
Total cost
€ 1 999 980,00

Beneficiaries (1)