CAREER: Biophysics of Flatworm Regeneration

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The most interesting aspect of living beings is the ability of biological tissues to generate and maintain their shape. Understanding how cells are able to create organs of a tightly-specified 3-dimensional geometry will have great benefits for biomedicine (helping to address cancer, regeneration, and aging). Even more interestingly, decoding the signals that control cell behavior will profoundly increase our understanding of the most basic properties of cell function and of the evolution of pattern-formation mechanisms. Making progress in this area requires a model system--a biological context amenable to the most powerful cell-biological and physiological techniques of the molecular age. The proposed work centers around a fascinating organism, the planarian. These free-living flatworms possess a truly remarkable property: they are able to regenerate any missing piece of the worm. Genomic approaches are beginning to address this phenomenon from a biochemical perspective. Interestingly, preliminary data indicated that a novel, biophysical, aspect of biological control was responsible for the ability of the worm's stem cells to correctly restore lost tissue: a natural electric field produced by the activity of ion channels and pumps in key cells. The project will use cell- and molecular-biological approaches to understand how natural ion flows direct stem cells to restore missing tissues; a variety of students and post-doctoral fellows will be involved. Additionally, the flatworm represents a very rich yet inexpensive system for introducing students at all levels to fundamental methods in biological discovery. The project includes an important educational component which will create a web-based center for the dissemination of materials, protocols, and results to high-school, college, and graduate student labs. The proposed center will ignite the interest of young scientists in profound problems of biological patterning and provide an opportunity for many to participate and gain hands-on experience in state-of-the-art techniques.