Completed Cells, Biochemistry & Physiology Genetics & Molecular Biology

Regulation and transduction of cell polarity.

In plain English

AI plain-English summary

A single fertilised worm egg is revealing how cells decide which end is up—a process that, when it goes wrong, can turn a healthy cell into a cancerous one. The one-celled embryo of the microscopic roundworm *C. elegans* is a stripped-down model for studying cell polarity: how a cell establishes a front and back, top and bottom. This spatial organisation is essential for everything from cell division to tissue formation. When polarity breaks down, cells can lose their identity and begin dividing uncontrollably—a hallmark of cancer. The researchers already know some of the molecules involved, but the initial trigger—the cue that tells a cell which way is which—remains unknown. This project will run systematic genetic screens to find that cue, study newly discovered regulators of the motor protein myosin, and map the full network of genes that build and transmit polarity signals. The work is fundamental science. It will not produce a drug or a diagnostic tool. But understanding the basic wiring of cell polarity has, in the past, revealed targets for cancer therapies and principles that govern how tissues repair themselves. A complete map of this network could eventually help explain why some cells become malignant and how to stop them.

View original technical description
Cell polarity is critical for many functions of animal cells and loss of cell polarity is a contributing factor in cancer. We are exploiting the one-celled C. elegans embryo to investigate conserved mechanisms of cell polarity establishment and transduction. It allows study of the polarity cue and its reception by the actomyosin cytoskeleton, of the polarisation events that occur in response to the polarity cue, and of how polarisation leads to downstream events such as asymmetric spindle posi tioning. I propose both focused projects that have come out of our current studies and new screens to identify missing molecules in the cell polarity network. We will (1) carry out directed screens to identify the initial polarity cue, (2) study newly identified regulators of non-muscle myosin, and (3) investigate roles for phosphoinositides in asymmetric spindle positioning. With a long-term goal of finding the complete set of genes functioning in these processes and their relationships, we w ill (4) apply high-throughput genetic interaction RNAi screening genome-wide together with (5) biochemical purifications to further expand the cell polarity network. (6) We will carry out functional studies of newly identified genes, taking advantage of C.elegans genetics, genomics and cell biology.

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Researchers

Julie Ahringer (EPMC Awardee)

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Original classification

Senior Research Fellowship Basic Renewal

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