Spatiotemporal Dynamics of Mitochondrial Populations: from Social to Physical Networks

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.