Project description
The transparent zebrafish reveals details about extracellular vesicle-mediated organ crosstalk
Our knowledge of cell signalling via circulating metabolic hormones underlying homeostasis (maintenance of the overall functioning of an organism at “normal” levels) is extensive. More recently, new methods of interorgan crosstalk have emerged as important regulators of health and disease. Extracellular vesicles (EVs) that encapsulate and move bioactive cargo between cells likely play a key role, but studying this experimentally is challenging. The ERC-funded CROSSTALK project will do so using a well-known and well-characterised model system, the transparent zebrafish. Focusing on EVs secreted by the liver, the central metabolic hub in vertebrates, the project will achieve the first advanced mapping of endogenous EV inter-organ crosstalk in a living model organism.
Objective
To coordinate activities between different tissues, multicellular organisms critically rely on intercellular communication. Whereas homeostatic signalling within organs is studied extensively, inter-organ crosstalk is only starting to be unravelled. In recent years, Extracellular Vesicles (EVs) have emerged as central mediators of this pathway by shuttling specific bioactive cargo including proteins between cells. These nano-sized lipid vesicles are released by virtually every cell type, are transported via the blood and combine the intricacy of cell-cell contact with the long-acting range of cytokines. However, due to their small size and a lack of suitable approaches, to what extent endogenous EVs mediate inter-organ crosstalk and support custom cargo delivery is unclear.
I recently developed a unique transparent zebrafish embryo model expressing optical EV-reporters to examine endogenous EV biology at unprecedented detail in vivo.
The aim of this proposal is to understand endogenous EV-mediated organ crosstalk by studying EVs secreted by the liver, the central metabolic hub in vertebrates. To this end, I will decode hepatic EV communication routes in vivo in health and liver pathology by exploiting my model system combined with novel tools and high-resolution microscopy. I will pursue three key-objectives: 1) Targets: mapping hepatic EV target organs; 2) Contents: analysing custom cargo delivery by hepatic EVs to specific target organs. 3) Function: determining the function of endogenous hepatic EVs by developing and applying molecular tools to interfere with their release in vivo.
This project will provide the first advanced mapping of endogenous EV inter-organ crosstalk in a living model organism. By studying how pathology impacts EV mediated organ crosstalk and gaining precise control over EV release in vivo I will obtain unique insights into EV pathophysiology. In turn, this will open avenues for optimized diagnostics and therapeutic intervention.
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 basic medicine physiology pathophysiology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- medical and health sciences basic medicine pathology
- medical and health sciences clinical medicine embryology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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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)
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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
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(opens in new window) ERC-2022-STG
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3584 CS Utrecht
Netherlands
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