NSF-Simons Center for Multiscale Cell Fate Research

加州大学欧文分校的NSF-Simons多尺度细胞命运研究中心将为创新团队在数学和生物学之间的界面研究提供一个刺激和授权的智力和物理环境。细胞的命运——分化为特定的生物细胞类型——是由几个相互关联的因素决定的：细胞内在机制、来自细胞外局部环境的信号，以及细胞从其他细胞接收到的信息。尽管在单细胞分辨率上获得了前所未有的大量实验数据，但细胞命运是如何决定的仍未完全了解。理论发展的挑战来自于多个时空尺度上的信息串扰，以及需要挖掘、整合和建模来自实验测量的新的单细胞“大数据”。为了应对这些挑战并建立多尺度细胞命运研究的基础范式，一个由数学科学家和生物学家组成的团队将开发新的数学、计算和统计工具，通过多尺度镜头分析细胞命运。该中心将在社区建设、跨学科培训和劳动力发展以及多样性增强方面开展连贯的计划，以扩大数学与生物的界面，促进数学与生物科学的融合。该中心将培养一批相互联系的年轻研究人员，并将在全国范围内培育下一代实验室。所获得的知识将为分析大数据和建模复杂系统创造新的多尺度数学，并在再生医学、胚胎发育和出生缺陷方面有更广泛的应用。NSF-Simons多尺度细胞命运研究中心将通过研究细胞跨尺度的新行为，建立对细胞命运控制机制和原理的新理解。该研究旨在深入了解细胞命运，重点关注三个生物学主题：皮肤细胞的复杂性和可塑性，神经嵴细胞的随机动力学和迁移，以及干细胞规范的表观遗传控制。虽然每个主题都解决了对细胞命运理解的不同差距，但它们都强调了多尺度相互作用产生的新兴复杂性，并且它们在数学方面有几个共同点。该中心旨在开发由这些特定细胞命运问题以及更广泛的生物学应用驱动的新的数学方法。数据驱动和基于原理的细胞命运多尺度模型将指导实验，并对建模工作进行后续反馈。为了提高数学和生物学之间的研究和培训的整体能力，将采取三种协调一致的努力：1)扩展接近生物学界面的数学科学，2)连接跨谱的数学科学家，以及3)培养数学科学家直接连接实验的能力。为实现中心的宏伟目标，将开发和实施一系列新的紧密联系的社区建设和推广项目，包括社区发起的跨学科机会奖、具有全国影响力的融合加速器团队项目、关于实验技术的生物桥诊所和通过学习研究为高中生提供数学体验的项目。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。

The NSF-Simons Center for Multiscale Cell Fate Research at the University of California, Irvine will provide a stimulating and empowering intellectual and physical environment for innovative team research at the interface between mathematics and biology. A cell's fate -- differentiation into a specific biological cell type -- is determined by several interlinked factors: cell-intrinsic mechanisms, signals from the local environment outside the cell, and messages the cell receives from other cells. Despite unprecedented amounts of experimental data at single-cell resolution, how cell fate is determined remains not fully understood. Challenges to development of a theory arise from information crosstalk at multiple temporal and spatial scales, as well as from the need to mine, integrate, and model the new single-cell "big data" derived from experimental measurements. To address these challenges and to establish a founding paradigm for multiscale cell fate research, a team of mathematical scientists and biologists will develop novel mathematical, computational, and statistical tools to analyze cell fate through a multiscale lens. The Center will carry out a coherent program for community building, interdisciplinary training and workforce development, and diversity enhancement to expand the mathematics-biology interface and to promote the convergence of mathematical and biological sciences. The Center will produce cohorts of interconnected young researchers and will nationally seed the next generation's laboratories. The knowledge gained will create new multiscale mathematics for analyzing big data and modeling complex systems, with broader applications to regenerative medicine, embryonic development, and birth defects.The NSF-Simons Center for Multiscale Cell Fate Research will establish new understanding of mechanisms and principles of cell fate control through investigation of emerging behavior of cells across scales. The study aims for transformative insight into cell fate, with a focus on three biological themes: cellular complexity and plasticity in skin, stochastic dynamics and migration of neural crest cells, and epigenetic control of stem cell specification. While each theme addresses different gaps in understanding of cell fate, they all emphasize emergent complexity arising from multiscale interactions, and they share several mathematical aspects. The Center aims to develop new mathematical methods driven by these specific cell-fate questions as well as broader biological applications. Data-driven and principle-based multiscale models of cell fate will guide experiments, with subsequent feedback to the modeling efforts. Three concerted efforts will be made to enhance overall capacity of research and training at the interface between mathematics and biology: 1) expanding mathematical sciences proximal to the biology interface, 2) connecting mathematical scientists across the spectrum, and 3) fostering mathematical scientists' ability to connect directly to experiments. A wide range of new and closely interconnected community-building and outreach programs, including community-initiated Interdisciplinary Opportunity Awards, a Convergence Accelerator Team program with national reach, a BioBridge Clinic on experimental techniques, and a Mathematical Experience through Learning Research program for high school students, will be developed and implemented to achieve the Center's ambitious goals.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.