Mucociliary adaptations and gut microbiome establishment in Xenopus

Introduction

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.

Project Goals

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.

Research Focus

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.

Hypothesis

We hypothesize that key epigenetic, patterning, and remodeling mechanisms are used in a modified fashion to generate different functions and morphologies in different organs.

Methodology

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.

1. We will test a series of hypotheses experimentally to gain insights into the mechanisms regulating mucociliary cell type compositions and their adaptations.
2. We will model mucociliary patterning in silico.
3. 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.

Techniques and Impact

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. This research aims to provide translational insights into human diseases that kill over 8 million people per year, including chronic airway diseases, cancers, and motile ciliopathies.