Spatiotemporal Dynamics of Mitochondrial Populations: from Social to Physical Networks

线粒体群体的时空动态：从社会网络到物理网络

• 批准号: 2310229
• 负责人: Elena Koslover
• 金额: $ 75.35万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2310229&HistoricalAwards=false
• 关键词: Spatiotemporal; Dynamics; Mitochondrial; Populations; Social

Mitochondria, the energetic powerhouses of eukaryotic cells, play a critical role in maintaining cell health and function. These organelles exhibit a variety of dynamic behaviors, including motor-driven transport, fusion, fission, and autophagic recycling. The balance of mitochondrial fusion and fission varies between different cell types and environmental conditions, allowing for the formation of both topologically connected physical networks and social networks of globular units that engage in transient interactions. As a population, mitochondria must be able to rapidly deliver signals and metabolic products to far-flung cellular regions, to maintain their own health and energy-producing capacity, and to respond in a concerted manner to environment changes. This award will develop a fundamental understanding of how the dynamics of mitochondrial populations gives rise to their spatial structure and mediates the transport of material through the population. The research approach will focus on the development of mathematical and physical models that link morphology and mixing dynamics on networks. The award aims for a general framework that will tie together behavior of social and physical networks. These models will help establish how a wide variety of mitochondrial features arises from a handful of basic parameters, including local fusion and fission rates, processive transport rates, and the geometry of the cellular domain. The theoretical work will be carried out in close collaboration with experimental measurements of mitochondrial populations. This work will deepen our understanding of a functionally critical organelle population whose structure and dynamics play a fundamentally important role in cellular health and whose perturbations are associated with a broad variety of human disorders, from neuropathies to cancer and aging.An integrated educational program will be developed to promote student interest and competency in cross-disciplinary scientific inquiry, targeting elementary to undergraduate students. This program will feature the Young Scientist’s Club (YSC) run by the PI at a local elementary school, which enrolls 2nd and 3rd grade students for two sessions a year. During the YSC meetings, students learn about key concepts that span across physics, chemistry, and biology, and engage in hands-on activities that illustrate those concepts. These research opportunities will enable students to acquire skills in data processing and numerical simulation, as well as gain exposure to interdisciplinary research.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.

线粒体是真核细胞的能量来源，在维持细胞健康和功能方面起着关键作用。这些细胞器表现出多种动力学行为，包括马达驱动的运输、融合、分裂和自噬循环。线粒体融合和分裂的平衡在不同的细胞类型和环境条件下会有所不同，从而形成拓扑连接的物理网络和参与短暂相互作用的球状单位的社交网络。作为一个群体，线粒体必须能够迅速将信号和代谢产物传递到遥远的细胞区域，以保持自身的健康和能量生产能力，并以协调一致的方式对环境变化做出反应。该奖项将对线粒体种群的动态如何产生其空间结构并介导物质通过种群的运输有一个基本的了解。研究方法将侧重于数学和物理模型的发展，连接形态和网络上的混合动力学。该奖项旨在建立一个通用框架，将社交网络和物理网络的行为联系在一起。这些模型将有助于确定各种各样的线粒体特征是如何从一些基本参数中产生的，这些参数包括局部融合和裂变速率、进行性运输速率和细胞结构域的几何形状。理论工作将与线粒体种群的实验测量密切合作进行。这项工作将加深我们对功能关键细胞器群体的理解，细胞器群体的结构和动力学在细胞健康中起着根本性的重要作用，其扰动与从神经病到癌症和衰老的各种人类疾病有关。将开发一个综合教育计划，以促进学生对跨学科科学探究的兴趣和能力，目标是小学到本科生。该计划将以PI在当地一所小学开办的青年科学家俱乐部（YSC）为特色，该俱乐部每年招收二年级和三年级学生两次。在YSC会议期间，学生学习跨越物理，化学和生物学的关键概念，并参与说明这些概念的实践活动。这些研究机会将使学生获得数据处理和数值模拟方面的技能，并获得跨学科研究的机会。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。