Kidneys in a dish: epithelial polarity and tube formation in human renal organoids
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Epithelia constitute one of the major tissue types in all animals and form the basic building blocks of tubular organs in both vertebrates and invertebrates. Simple epithelial sheets are also the starting point in the development of most animals. In the lab, we want to dissect how simple epithelial sheets deform in a highly concerted manner to turn into complex tubular tissue shapes, and also how de novo formation of epithelial polarity allows for the formation of tubular organs.
We have recently adapted protocols to grow human renal/kidney organoids in the lab (see original references below). These organoids recapitulate many aspects of human first trimester kidney morphogenesis, including formation of a renal vesicle, tube elongation and segmentation into functional units resembling proximal and distal tubule, loop of Henle and podocytes.
This project will utilise renal organoids to address fundamental cell biological questions of how cell-cell adhesion and cytoskeletal control allow for highly concerted behaviours during tube formation, and how the morphological changes are integrated with changes at the transcriptome level. We will also utilise advanced imaging methods to study these processes live.
Little, M. H., Kumar, S. V., & Forbes, T. (2018).
Recapitulating kidney development: Progress and challenges.
Seminars in Cell & Developmental Biology. http://doi.org/10.1016/j.semcdb.2018.08.015
Takasato, M., Er, P. X., Chiu, H. S., Maier, B., Baillie, G. J., Ferguson, C., et al. (2015).
Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis.
Nature, 526(7574), 564–568. http://doi.org/10.1038/nature15695