Nerve cells communicate by sending electrical impulses along thin protrusions called axons. One mechanism by which animals increase velocity of electrical impulses is to expand axons' cross-sectional area. This expansion is caused by an accumulation of microscopic space-filling protein polymers called neurofilaments, which are transported into axons where they form a dynamic scaffold. This collaborative project will use microscopic imaging in conjunction with computational modeling to test the hypothesis that neurofilament accumulation in axons is caused by a slowing of neurofilament transport, much as cars pile up on highways when the traffic slows. This project will provide a rigorous and quantitative framework that relates the size and shape of axons, which is a key influence on their electrical properties, to the motile behavior of their internal constituents. This work will also shed light on the mechanism by which neurofilaments accumulate abnormally and excessively within axons in many neurodegenerative diseases.
This project will provide a unique training opportunity at the interface of computational and experimental biology for students with diverse backgrounds in the physical and life sciences. An emphasis will be placed on mentoring undergraduates lacking prior research experience, including women and minorities, through annual Research Experiences for Undergraduates fellowships. The investigators will also reach out to undergraduates by participating together in the Research for Undergraduates: Adventures in Mathematical Biology and its Applications curriculum at Ohio State University, which is an NSF-funded Undergraduate Biology and Mathematics program, and by serving as joint mentors in the Undergraduate Summer Research Program of the NSF-funded Mathematical Biosciences Institute at Ohio State University. Lastly, a neurofilament wiki page will be developed featuring information and resources on mathematical modeling of axonal transport to support these outreach activities and to facilitate the exchange of data between the two laboratories.
