CAREER: Mathematical Modeling and Computational Tools for in vivo Astrocyte Activity

本项目旨在开发新的计算工具来解释和分析星形胶质细胞的活动。星形胶质细胞是一种神经胶质细胞，也是大脑中数量最多的细胞，最近发现它比以前认为的具有更活跃的功能。星形胶质细胞密切倾听并主动调节神经系统，但它们在正常和病理大脑中的确切作用尚不清楚。最近的技术进步使得以前所未有的空间和时间分辨率监测星形胶质细胞活动成为可能，但考虑到星形胶质细胞活动数据的复杂性和规模，严格的计算建模是至关重要的。该项目将为星形胶质细胞活性的定量分析奠定坚实的基础，使体内分析成为可能，具有更高的可重复性，并有利于了解大脑疾病。在这个项目中提出的具有计算挑战性的问题有望对计算机科学的其他领域有价值，作为建立新的统计模型和开发强大的通用机器学习理论和算法的例子。拟议的研究将开发一个全面的数据驱动框架来模拟星形胶质细胞活动，其具体目标是自动检测钙事件，识别功能独立单位并表征其个体和系统表现。三个研究目标包括：(1)开发检测钙事件的计算方法；(2)星形胶质细胞活性的系统建模和量化；(3)应用于小鼠和其他模型动物的体内星形胶质细胞，通过解决几个不同的当前生物学问题来展示所提出方法的实用性。教育目标是帮助维持美国计算神经科学劳动力的竞争活力，并通过将前沿计算神经科学问题纳入工程课程，通过改善女性和少数民族学生的招聘和保留，通过接触K-12学生激发他们对这一跨学科领域的兴趣，加深对核心计算概念的理解。通过与本科生互动，提供机会并鼓励他们选择计算神经科学作为职业。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project aims to develop new computational tools to interpret and analyze the activity of astrocytes. Astrocytes, one type of glial cells and the most populous cells in brain, have recently been found to have much more active functionality than previously thought. Astrocytes closely listen to and proactively regulate the nervous system, yet their exact roles in normal and pathological brains remain elusive. Recent technological progress makes it possible to monitor astrocyte activity with unprecedented spatial and temporal resolution, but considering the complexity and scale of astrocyte activity data, rigorous computational modeling is critically needed. This project will establish a solid foundation for quantitative analysis of astrocyte activity, enabling in vivo analysis, greater reproducibility, and benefits for understanding brain disorders. The computationally challenging problems formulated in this project are expected to be valuable for other areas of computer science, serving as examples to build new statistical models and develop powerful generic machine-learning theory and algorithms. The proposed research will develop a comprehensive data-driven framework to model astrocyte activity, with the specific goals of automatically detecting calcium events, identifying functional independent units and characterizing their individual and systems manifestation. Three research objectives include: (1) developing computational approaches to detect calcium events (2) systems modeling and quantification of astrocyte activity, and (3) application to in vivo astrocytes of mouse and other model animals to showcase the usefulness of the proposed methodology by addressing several different current biological questions. The educational objective is to help maintain the competitive vitality of the U.S. computational neuroscience workforce, and to deepen the understanding of core computational concepts, by incorporating cutting-edge computational neuroscience problems into the engineering curriculum, by improving the recruitment and retention of women and minority students, by reaching out to K-12 students to inspire their interest in this interdisciplinary field, and by interacting with undergraduate students to offer opportunities and encourage them to choose computational neuroscience as a career.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.