TUBEREMODELLING · Tubular organ remodelling during development, homeostasis and disease

Remodelling of tubular organs, like the lungs or blood vessels, encompasses the changes in both cell number and cell shape that lead to an altered organ form adapted to changes in developmental timing, injury or environmental cues. To understand how tubular organs are remodelled during development and disease, I will use as a model the Drosophila tracheal system, which is an extensive tubular network that functions as the lungs and blood vessels. Moreover, the similarity of the fly trachea with mammalian tubular organs extends to the cellular and molecular levels of tube formation, making findings in Drosophila applicable to mammalian biology. To study developmental remodelling, I characterized a set of multipotent progenitors, which respond to evolutionarily-conserved signals that coordinate cellular proliferation and differentiation to generate anew the tracheal system of the adult. In addition, I established in adult Drosophila an intestinal infection and tumorigenesis model. Strikingly, in this model the trachea that surrounds and oxygenates the diseased gut is extensively remodelled, sharing parallels with mammalian angiogenesis. By combining my knowledge of tracheal development and intestinal homeostasis, I aim to understand how signalling pathways interact to remodel epithelial tubular organs during development and disease. Understanding how tubular organs are formed and remodelled in a genetically-amenable model system like Drosophila will aid our understanding of the cause of developmental anomalies and diseases of tubular organs like dysplasias, polycystic kidney disease and tumor angiogenesis.Specifically, I will:Aim 1: Characterize the signalling network that coordinates proliferation and differentiation of tracheal progenitors during developmental remodelling.Aim 2: Identify novel molecules involved in tube remodelling during physiological and regenerative homeostasis as well as during tumorigenesis.