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Mucociliary adaptations and gut microbiome establishment in Xenopus

Project description

A closer look at cell type regulation for health and disease

The composition of different cell types determines how tissues function, evolve, and respond to disease. Yet, scientists still struggle to understand how these compositions can be controlled to influence organ function. A deeper understanding of these mechanisms could lead to breakthroughs in treating conditions like chronic airway diseases and cancers, which claim millions of lives annually. With this in mind, the ERC-funded MAGIX project seeks to unravel how cell type compositions are regulated during development and disease. Using mucociliary epithelia from Xenopus and mice as models, the project will investigate key genetic and epigenetic mechanisms, providing crucial insights into tissue adaptation and potential therapeutic applications.

Objective

Cell type compositions determine tissue morphologies and functions, are adapted during evolution, and their changes cause diseases. However, we do not understand how cell type compositions can be controlled and modified to predictively achieve different organ functions. The goal of the MAGIX project is to understand the developmental mechanisms controlling cell type compositions, and to mechanistically link variations of cell type compositions to physiological properties of tissues in development and disease. We will use mucociliary epithelia as they provide an optimal system to study how adaptations of cell type compositions are regulated and how they determine organ functions. They build on a conserved gene-regulatory network to generate epithelia with different functions across species and organs derived from all three germ layers. We hypothesize that key epigenetic, patterning and remodeling mechanisms are used in a modified fashion to generate different functions and morphologies in different organs. In this project, we will establish two new vertebrate mucociliary model systems in the Xenopus foregut and the mouse esophagus, multi-modal resources, and integratively analyze data across models. We will then test a series of hypotheses experimentally to gain insights into the mechanisms regulating mucociliary cell type compositions, their adaptations, and to model mucociliary patterning in silico. Lastly, the developmental functions of foregut mucociliary epithelia in Xenopus and mice will be investigated to reveal potential contributions to gut microbiome establishment, thereby uncovering a new role for mucociliary epithelia in vertebrate development. Using a range of state-of-the-art techniques, the MAGIX project will study mucociliary adaptations to resolve fundamental questions in cell and developmental biology, and to provide translational insights into human diseases that kill >8 Mio. people per year (chronic airway diseases, cancers, motile ciliopathies).

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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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.

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.

(opens in new window) ERC-2024-COG

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Host institution

UNIVERSITAETSKLINIKUM FREIBURG
Net EU contribution

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.

€ 1 995 921,00
Address
HUGSTETTER STRASSE 49
79106 Freiburg
Germany

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Region
Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 1 995 921,00

Beneficiaries (1)

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