Research

Genetics of tracheal tube size and shape
We carried out systematic chemical mutagenesis screens, in which we isolated mutations affecting various morphological features (tube length, diameter, luminal shape, tube fusion), as well as cellular processes (secretion, endocytosis, epithelial barrier function). The use of fluorescent marker proteins to visualize tracheal cells and lumen allowed for efficient and unbiased screening in living embryos. The mutations fall into a small number of distinct phenotypic classes, thus providing an entry point towards a comprehensive analysis of the mechanisms that control tubular size and shape. We use next-generation sequencing technology available at the Functional Genomics Centre Zurich to rapidly identify chemically induced mutations. New genes are characterized using genetic, cellular, and biochemical approaches. We have so far focused on the characterization of genes involved in extracellular matrix deposition during tracheal lumen expansion. We are currently extending the successful screening approach by including more specific readouts for epithelial structure and intracellular trafficking pathways.

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