Every organ in the human body starts as a simple cluster of cells that must coordinate their movements to form functional tubes—lungs, kidneys, glands—yet how this genetic choreography plays out at the scale of whole tissues remains unknown. This project tackles that gap by watching tube formation in two systems: the developing salivary gland of a fruit fly embryo and human kidney organoids grown in a dish. Both are epithelial tubes, and when tube formation fails, it can cause birth defects or fuel the spread of most cancers. The researchers will use live imaging, genetic tools, and physical manipulation to track how individual cells’ internal skeletons—the cytoskeleton—link up across hundreds of cells to bend and shape tissue. They will also ask how the genetic blueprint inside each cell feeds back into these mechanical forces. This is fundamental science: it will not produce a drug or device tomorrow. But understanding how cells collectively build organs could eventually guide efforts to repair damaged tissues, grow transplantable organs, or prevent the structural failures that allow cancers to invade.
View original technical description
How organ shape is genetically encoded remains a major unresolved question in biology. All tissues arise from simple primordia that become patterned through transcriptional changes within individual cells. Since organ form drives tissue function, revealing how cell-specific transcriptional changes trigger biochemical events at the nanometre-scale within individual cells that in turn result in highly coordinated changes of many cells at the tissue or micro-to- millimetre-scale is essential to understanding organ physiology. We leverage two complementary models of tube morphogenesis to understand supracellular coordination in morphogenesis. Most internal organs are epithelial and tubular, and failure in tube formation or homeostasis can lead to severe malformations and is the cause of most cancers. We combine as models the simple but highly tractable budding-morphogenesis of the salivary glands in the Drosophila embryo with the formation of a human tubular organ with great clinical importance, nephron morphogenesis in human renal organoids. Using a combination of quantitative imaging, physical interference, advanced genetic tools and sequencing approaches that we have established in both models, we will assess how coordination is implemented through supracellular cytoskeletal assemblies (RQ1), how cytoskeletal crosstalk mediates tissue-wide coordination (RQ2) and how the transcriptional blueprint establishes non-transcriptional coordination and feed-back through tissue mechanics (RQ3).
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know