Collaborative Research: Neurofilament Transport Kinetics and Axonal Morphology

神经细胞通过沿着被称为轴突的细突起发送电脉冲来进行交流。 动物增加电脉冲速度的一种机制是扩大轴突的横截面积。 这种扩张是由称为神经丝的微观空间填充蛋白质聚合物的积累引起的，这些蛋白质聚合物被运送到轴突中，在那里它们形成动态支架。这个合作项目将使用显微成像结合计算建模来测试假设，即轴突中的神经丝积累是由神经丝运输的减慢引起的，就像汽车在高速公路上堆积时交通减速一样。该项目将提供一个严格的定量框架，将轴突的大小和形状与其内部成分的运动行为联系起来，轴突的大小和形状是其电特性的关键影响因素。 这项工作也将阐明神经丝在许多神经退行性疾病中在轴突内异常和过度积累的机制。 该项目将为具有物理和生命科学不同背景的学生提供计算和实验生物学接口的独特培训机会。重点将放在辅导本科生缺乏以前的研究经验，包括妇女和少数民族，通过年度研究经验的本科生奖学金。研究人员还将接触到本科生一起参加研究本科生：数学生物学及其应用课程的冒险在俄亥俄州大学，这是一个NSF资助的本科生物学和数学计划，并担任联合导师在本科生暑期研究计划的NSF资助的数学生物科学研究所在俄亥俄州州立大学。最后，将开发一个神经丝wiki页面，提供轴突运输数学建模的信息和资源，以支持这些推广活动，并促进两个实验室之间的数据交换。

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.