Objective
Mammals display an abundant capacity for organ growth in the neonatal window but lose this capacity in adulthood. The adult liver maintains some regenerative capacity, but this remains far below the neonatal growth capacity. The adult liver can replenish up to 70% of its mass after surgical resection. However, resection of larger volumes induces liver failure, which causes death of one in three patients. For decades hepatologists have tried to pharmacologically augment hepatocyte proliferation to improve liver regeneration, yet all these attempts have failed. Our recent liver cell atlas revealed the modular architecture of the liver, with each module containing a dedicated macrophage and stromal cell. The primary hepatic module is composed of 4 cell types: hepatocytes, sinusoidal endothelial cells, stellate cells and Kupffer cells. We studied this 4-cell-circuit across seven species and found that throughout evolution these cells became so interdependent that they operate as one interconnected functional module. Stepping away from the conventional hepatocyte-centric view of liver regeneration, we propose a paradigm shift in which we hypothesize that the key to successful liver regeneration is to maintain the integrity of each liver module. Our preliminary data indicate that multiplication of neonatal cells happens synchronously, while adult generation is characterized by uncoupled multiplication of liver cells. We will track the multiplication of liver cells in space and time across different biological models, during the neonatal window and in adults upon surgery, to identify the mechanisms that underlie the synchronous multiplication of neonatal liver cells. We will develop high-throughput functional in vivo screens to manipulate the hepatic molecular circuits and identify pathways that can boost liver regeneration and maintain cellular functionality, with as ultimate goal to identify novel classes of therapeutic targets that can boost liver regeneration.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine surgery
- natural sciences biological sciences zoology mammalogy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
9052 ZWIJNAARDE - GENT
Belgium
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.