NSF-Simons Center for Multiscale Cell Fate Research

NSF-西蒙斯多尺度细胞命运研究中心

• 批准号: 1763272
• 负责人: Qing Nie
• 金额: $ 500万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1763272&HistoricalAwards=false
• 关键词: NSF; Simons; Center; Multiscale; Cell

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.

加州大学欧文分校的NSF-Simons多尺度细胞命运研究中心将为数学和生物之间的创新团队研究提供一个激励和赋能的智力和物理环境。细胞的命运--分化成特定的生物细胞类型--由几个相互关联的因素决定：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的信息。尽管在单细胞分辨率下获得了史无前例的大量实验数据，但细胞命运是如何决定的仍不完全清楚。对理论发展的挑战来自于多个时间和空间尺度上的信息串扰，以及对从实验测量得出的新的单细胞“大数据”进行挖掘、集成和建模的需要。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，通过多尺度透镜分析细胞命运。该中心将在社区建设、跨学科培训和劳动力发展以及加强多样性方面开展协调一致的计划，以扩大数学-生物学的接口，促进数学和生物科学的融合。该中心将培养一批相互联系的年轻研究人员，并将在全国范围内为下一代实验室提供种子。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得到更广泛的应用。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来建立对细胞命运控制机制和原理的新理解。这项研究旨在对细胞命运进行变革性的洞察，重点关注三个生物学主题：皮肤中的细胞复杂性和可塑性，神经脊细胞的随机动力学和迁移，以及干细胞规格的表观遗传控制。虽然每个主题都解决了对细胞命运理解上的不同差距，但它们都强调由多尺度相互作用产生的新出现的复杂性，并且它们有几个共同的数学方面。该中心的目标是开发由这些特定的细胞命运问题驱动的新的数学方法，以及更广泛的生物学应用。数据驱动和基于原理的细胞命运多尺度模型将指导实验，并随后对建模工作进行反馈。将作出三项共同努力，以提高数学和生物学接口的研究和培训的整体能力：1)扩大生物接口附近的数学科学，2)连接不同领域的数学科学家，3)培养数学科学家直接与实验联系的能力。为了实现中心雄心勃勃的目标，将开发和实施一系列新的密切相关的社区建设和外展计划，包括社区发起的跨学科机会奖、全国覆盖的融合加速器团队计划、实验技术生物桥诊所和数学学习研究计划。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

The M3 Muscarinic Acetylcholine Receptor Promotes Epidermal Differentiation.

• DOI: 10.1016/j.jid.2022.06.013
• 发表时间: 2022-12
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Duan, Junyan;Grando, Charles;Liu, Shuman;Chernyavsky, Alex;Chen, Jefferson K.;Andersen, Bogi;Grando, Sergei A.
• 通讯作者: Grando, Sergei A.

A human vascularized microtumor model of patient-derived colorectal cancer recapitulates clinical disease.

• DOI: 10.1016/j.trsl.2022.11.011
• 发表时间: 2023-05
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: Hachey SJ;Sobrino A;Lee JG;Jafari MD;Klempner SJ;Puttock EJ;Edwards RA;Lowengrub JS;Waterman ML;Zell JA;Hughes CCW
• 通讯作者: Hughes CCW

OVOL1 Regulates Psoriasis-Like Skin Inflammation and Epidermal Hyperplasia.

• DOI: 10.1016/j.jid.2020.10.025
• 发表时间: 2021-06
• 期刊: The Journal of investigative dermatology
• 作者: Sun P;Vu R;Dragan M;Haensel D;Gutierrez G;Nguyen Q;Greenberg E;Chen Z;Wu J;Atwood S;Pearlman E;Shi Y;Han W;Kessenbrock K;Dai X
• 通讯作者: Dai X

Efficient simulation of thermally fluctuating biopolymers immersed in fluids on 1-micron, 1-second scales

以 1 微米、1 秒的尺度有效模拟浸没在流体中的热波动生物聚合物

• DOI: 10.1016/j.jcp.2018.12.039
• 发表时间: 2019
• 期刊: Journal of Computational Physics
• 影响因子: 4.1
• 作者: Liu, Kai;Lowengrub, John;Allard, Jun
• 通讯作者: Allard, Jun

Receptor Organization Determines the Limits of Single-Cell Source Location Detection

受体组织决定单细胞源位置检测的极限

• DOI: 10.1103/physrevlett.125.018102
• 发表时间: 2020
• 期刊: Physical Review Letters
• 影响因子: 8.6
• 作者: Lawley, Sean D.;Lindsay, Alan E.;Miles, Christopher E.
• 通讯作者: Miles, Christopher E.