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。这种扩张是由被称为神经丝的微小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输到轴突中，在轴突中形成一个动态支架。这个合作项目将使用显微成像技术结合计算模型来验证一个假设，即神经丝在轴突中的积累是由神经丝运输的减缓引起的，就像交通减速时汽车在高速公路上堆积一样。该项目将提供一个严谨的定量框架，将轴突的大小和形状与它们内部成分的运动行为联系起来，轴突的大小和形状是影响它们电学特性的关键因素。这项工作也将阐明在许多神经退行性疾病中，神经丝在轴突内异常和过度积累的机制。该项目将为具有不同物理和生命科学背景的学生提供一个独特的计算生物学和实验生物学界面的训练机会。通过年度本科生研究经验奖学金，重点将放在指导缺乏先前研究经验的本科生，包括女性和少数民族。研究人员还将通过共同参与俄亥俄州立大学的本科生研究：数学生物学冒险及其应用课程（这是美国国家科学基金会资助的本科生生物学和数学项目），以及作为美国国家科学基金会资助的俄亥俄州立大学数学生物科学研究所本科生暑期研究项目的联合导师，来接触本科生。最后，将开发一个神经丝维基页面，提供轴突运输数学建模的信息和资源，以支持这些外展活动，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.