权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

RUI: Physics of Cytoskeletal Organization in Neural Development

RUI：神经发育中细胞骨架组织的物理学

基本信息

批准号：
1915477
负责人：
Erin Craig Ricketson
金额：
$ 19.32万
依托单位：
Central Washington University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1915477&HistoricalAwards=false
关键词：
RUI Physics Cytoskeletal Organization Neural

项目摘要

Neurons are specialized cells that transmit electrical impulses to control heart rate, movement, and higher brain function. A complex network of neurons must be "wired" properly to support the spatial and temporal coordination of neural signals. During nervous system development, neurons project fibers called axons, which undergo directed growth to form connections with other cells. A network of dynamic protein filaments called the cytoskeleton facilitates several distinct mechanical functions underlying axonal outgrowth and development. The goal of this project is to apply computational models to better understand how forces and movements in the cytoskeleton mediate neural development and function. The project will provide training to a diverse group of undergraduate students at a regional comprehensive university that is approximately 95% undergraduate, 40% first-generation college students, and 20% from underrepresented minorities. The proposed project will build on the impact of existing university programs that provide research opportunities for students from underrepresented groups. Undergraduate students involved in the research will have the opportunity to become immersed in basic research full time for two months during the summer (10-12 students over the funding period). The PI has developed several novel courses at the boundary of physics and biology, and has developed and led interdisciplinary science outreach workshops designed to engage low-income students and other underrepresented groups in STEM fields.The PI will develop agent-based computational models to investigate cytoskeletal organization and mechanical function in developing neurons, with particular emphasis on two distinct neuronal compartments: (1) a slender fiber called an axon, along which neural impulses are conducted from the cell body to other cells; and (2) a sensory-motile structure at the tips of axons called a growth cone, which guides axonal outgrowth during development or regeneration. These regions of the neuron both contain many of the same cytoskeletal components, but in each context these molecular components are repurposed for functionally distinct mechanical tasks. Novel mechanical models will be developed to investigate emergent behavior that arises on a systems level from the molecular scale interaction of the parts. The models will be tested and refined in close collaboration with experimental colleagues, and model predictions will guide the design of new experiments. The project will address fundamental mechanistic questions about developing neurons, including: How do axons grow in the correct direction during embryogenesis to form the appropriate connections with other cells? How do growing axons develop and maintain an organized internal structure capable of facilitating directed intracellular transport of neurotransmitters and other cellular vesicles? When cytoskeletal organization in axons is disrupted due to disease or injury, what mechanisms may contribute to axonal repair? Specific objectives are: (1) Investigate how cytoskeletal filaments and growth cone substrate adhesion are coordinated to facilitate growth cone steering in response to chemical guidance cues; (2) Investigate how developing axons establish and maintain an organized array of polar microtubule filaments that is essential to support healthy nervous system function.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

神经元是一种特殊的细胞，可以传输电脉冲来控制心率，运动和更高的大脑功能。复杂的神经元网络必须正确“布线”，以支持神经信号的空间和时间协调。在神经系统发育过程中，神经元投射称为轴突的纤维，轴突进行定向生长以与其他细胞形成连接。称为细胞骨架的动态蛋白丝网络促进轴突生长和发育的几种不同的机械功能。该项目的目标是应用计算模型来更好地理解细胞骨架中的力和运动如何介导神经发育和功能。该项目将在一所区域综合大学为不同的本科生群体提供培训，其中约95%为本科生，40%为第一代大学生，20%来自代表性不足的少数民族。拟议的项目将建立在现有大学课程的影响，为代表性不足的群体的学生提供研究机会。参与研究的本科生将有机会在夏季全职沉浸在基础研究中两个月（资助期间10-12名学生）。PI开发了几门物理学和生物学领域的新课程，并开发和领导了跨学科科学外展研讨会，旨在吸引低收入学生和其他STEM领域代表性不足的群体。PI将开发基于代理的计算模型，以研究发育中神经元的细胞骨架组织和机械功能，特别强调两个不同的神经元隔室：（1）称为轴突的细长纤维，神经冲动从细胞体沿其沿着传导到其他细胞;（2）位于轴突顶端的称为生长锥的感觉运动结构，其在发育或再生期间引导轴突生长。神经元的这些区域都包含许多相同的细胞骨架成分，但在每种情况下，这些分子成分都被重新用于功能不同的机械任务。将开发新的力学模型来研究从分子尺度的部件相互作用在系统水平上产生的紧急行为。模型将与实验同事密切合作进行测试和改进，模型预测将指导新实验的设计。该项目将解决有关神经元发育的基本机制问题，包括：在胚胎发育过程中，轴突如何以正确的方向生长，以形成与其他细胞的适当连接？生长中的轴突是如何发展和维持一个有组织的内部结构，能够促进神经递质和其他细胞囊泡的定向细胞内运输的？当轴突中的细胞骨架组织由于疾病或损伤而被破坏时，什么机制可能有助于轴突修复？具体目标是：（1）研究细胞骨架丝和生长锥基质粘附如何协调以促进生长锥响应化学引导线索的转向;（二）研究发育中的轴突如何建立和维持一个有组织的极性微管细丝阵列，这对支持健康的神经系统功能至关重要。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准。