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Research group Group Samakovlis

Branched tubular organs are found in most animals. They include tissues like the lung, kidney and the vascular system. Many of the basic principles of tube construction in these organs are conserved among species. We aim to describe the genetic programs leading to the formation of a functional epithelial tubular network.

Group description

The Drosophila airways, the trachea, form a complex tubular system that delivers air directly to all tissues in the animal. Our work utilizes genetics, bioinformatics and live imaging in Drosophila to characterize the molecular control of tube size and epithelial organ maturation.

Research projects

Tube maturation: From morphogenesis to function
The development of air-filled respiratory organs is crucial for survival. We have combined live imaging with genetics to dissect airway maturation. Initially, a secretion burst deposits proteins into the nascent tracheal tubes. Solid material is then rapidly cleared and shortly thereafter liquid is removed from the lumen. The mechanisms underlying the precise spatial and temporal regulation of epithelial activities during airway maturation are unknown. We have used a tracheal specific driver and ~20000 transgenic UAS-RNAi strains to first describe all protein-coding genes involved in the process. To identify the developmental regulators of airway maturation, we preselected about 600 genes encoding putative regulators and further classified these genes into 12 groups based on the defects in tube morphologies, apical secretion and protein clearance events caused by their tracheal inactivation. The combination of this phenotypic analysis with the data from protein interaction databases reveals new gene regulatory networks controlling airway maturation.

Lung Development and Regeneration
Epithelial cells in the lung form a highly organized tubular network exposed to air, pollutants and pathogens to facilitate breathing. To elucidate the genetic blueprint of airway cell differentiation and morphogenesis we combine the powerful genetic tools available in Drosophila airways with live imaging and single cell transcriptomics in the developing mouse and human lung. A major aim is to identify the cellular heterogeneity and plasticity in the lung epithelium during homeostasis and upon injury or infection. Mechanistic studies in flies, showed that the selection of differentiated and multipotent stem cells in the airway tree relies on a sensitive balance of Wingless, Hedgehog and RTK signaling. Our single cell mRNA sequencing of lung epithelial cells and in situ sequencing experiments in mice revealed a large variety of airway cells and their candidate cell fate regulators. We now use genetics, live imaging of mouse lung slices and cultures of human bronchial cells to probe the regulatory circuits that select and maintain distinct populations of stem- and differentiated cells.

Lung diseases, including cancer are among the leading causes of death worldwide with still unmet treatment challenges. Using high-resolution, single cell analysis technologies we hope to understand the cellular and molecular programs leading to normal lung development and to discover how these programs become misdirected to cause terminal lung diseases.