Project description
Understanding stem cell communication in the ageing gut
Intestinal stem cells (ISCs) communicate closely with neighbouring Paneth cells to maintain their health and functionality. Paneth cells support ISCs by providing molecular cues that direct their growth and differentiation. As people age, this communication weakens, contributing to inflammation and disease. With the support of the Marie Skłodowska-Curie Actions programme, the GRIPP project will investigate how these signals are delivered to the cell surface and how this process changes over time. Researchers will employ advanced imaging and genetically modified organoids to monitor and manipulate the secretory pathways of ISCs and Paneth cells. The goal is to understand and ultimately reverse this age-related decline in intestinal function.
Objective
Intercellular communication between epithelial intestinal stem cells (ISCs) and their niche Paneth cells is essential for intestinal homeostasis. It deteriorates with age promoting disease onset such as inflammation and cancer. Thus, understanding age-associated alterations in stem-niche cell communication is crucial for developing interventions to optimize tissue function in later years.
To communicate, Paneth cells secrete ligands instructing proliferation and differentiation of ISCs. ISCs receive these ligands via the respective receptors on their plasma membrane. While the signaling pathways of their communication are comprehensively described, the secretory membrane transport from the inside of the cell towards the cell surface of the ligands and receptors are only poorly understood.
This project will identify how ISCs and their niche cells direct the secretory transport of receptor and ligand proteins for efficient intercellular communication at the cell surface and how directed secretion functions as an intestinal homeostasis regulator. First, I will establish a novel optogenetic tool in intestinal organoids enabling spatiotemporal resolved tracing of synchronized signal secretion in ISCs and niche Paneth cells using live imaging. Second, I will reroute directed secretory transport by addition of GPI-anchors, targeted signaling motif and gene removal. In combination with transcriptomics, I will study the effects of disturbed secretion on intestinal homeostasis. Third, I will unveil alterations in directed secretory transport with age and age-related dysfunctions.
The proposed project will elucidate how directed secretory transport between ISCs and their neighboring niche cells determines stem cell function for tissue homeostasis. Overall, it holds the potential to uncover age-related changes in directed signal secretion, opening new avenues for treatments improving age-associated intestinal dysfunction.
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.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- 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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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80539 MUNCHEN
Germany
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