CAREER: Integrated Models of Neural Axon Guidance

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1055990, MooreProper functioning of the central nervous system is dependent on accurate connections between nerve cells. During both development and repair, nerves navigate toward intended targets by responding to numerous physical and molecular signals from their microenvironment. For example, it has been shown that nerve cells from the retina are attracted toward the optic tract by a chemical called netrin-1 that diffuses through the tissue forming a concentration gradient. These same nerve cells are later influenced to follow a path toward one side of the brain or the other by repulsion from another chemical called ephrin-B2 that is bound to the tissue in a specific location. The precise mechanisms by which cells integrate multiple signals remain unclear, partly because the experimental methods to test such mechanisms have relied heavily upon difficult cell preparations. Synthetic biomaterials are poised as means to more easily and quantitatively control the spatial distribution of physical and molecular guidance cues. The purpose of this proposal is to make use of new photoreactive biomaterials along with computer simulation to develop an integrated model of nerve growth in response to structural and molecular cues in the microenvironment. The models developed will enable unprecedented control of multiple guidance cues, enabling further investigation into how they influence axon guidance. The research proposed in this application may benefit society by enabling quantitative, more readily-implementable techniques that may aid discovery of biological mechanisms important for embryonic development, neurological disorders, and regeneration processes. Further, the novel biomaterials developed may find use in many unforeseen applications. Educational impacts will also be realized by this proposal. Numerous graduate and undergraduate students will be educated in the investigator?s laboratory, and the techniques developed will be introduced into a course taken by graduate and undergraduate students. The research lab will also serve as a hub for promoting career opportunities in science, engineering, technology, and mathematics to students and teachers in underrepresented minority-serving schools in Louisiana. This will be accomplished through summer research experiences provided to undergraduate students in underrepresented groups as well as to high school teachers in minority-serving high schools in the New Orleans area.