Project description
Molecular characterisation of macrophages in the liver
Macrophages are specialised immune cells capable of phagocytosing pathogens and activating T cell-mediated responses. They are present in different organs including the lung and the brain and perform specific functions. The EU-funded Liver ID3ntity project focuses on Kupffer cells, the macrophages of the liver. Researchers are interested to determine the molecular mechanisms that drive Kupffer cell function and how these are driven by the interaction with liver cells. The project will evolve around ID3, a key transcription factor of Kupffer cell identity, and offer fundamental knowledge in liver homeostasis and pathology.
Objective
Macrophages perform unique tissue-specific functions that are essential for the homeostasis of each organ. To perform these tissue-specific functions, each resident macrophage expresses a relatively unique gene expression profile controlled by specific transcription factors. Kupffer cells (KCs) are the biggest macrophage population of the body and represent 10% of all liver cells. The Guilliams lab recently reported that each KC projects an important part of its body across the liver endothelial cell barrier to be in close contact with hepatocytes. We have established that the transcription factor ID3 is highly expressed in murine KCs as compared to other macrophages, is highly preserved in KCs across 5 different species and is essential for controlling KC identity in vivo. We have recently reported that monocytes co-cultured with hepatocytes, but not with liver endothelial cells or liver fibroblasts, acquire strong ID3 expression, indicating that hepatocyte-derived signals induce ID3 expression. The objective of this proposal is to utilise ID3-expression in KCs to unravel the molecular mechanisms underlying the KC-Hepatocyte crosstalk. Since nothing is known about the hepatocyte-derived signals that induce ID3 expression in myeloid cells, I will utilize a genome-wide in vitro CRISPR screen to identify positive and negative regulators of the ID3 expression induced by hepatocytes. The result of this in vitro ID3-screen will then be combined with potential regulators predicted through epigenetic and ligand-receptor inference algorithms, to obtain our top candidates for genes involved in the liver KC-Hepatocyte crosstalk. Using cutting-edge technology combining direct guide-RNA capture with single-cell RNA sequencing, I will then perform a targeted in vivo CRISPR screen. Finally, I will knock-down the most interesting hits from this in vivo screen using CRE-Lox technology to understand the role of specific KC-Hepatocyte interactions in liver homeostasis and pathology.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences cell biology cell signaling
- medical and health sciences basic medicine physiology homeostasis
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2020
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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.