CAREER:'Understand the Multiplexing and Communication in Multicellular Sensory Response

职业：“了解多细胞感觉反应中的复用和通信”

• 批准号: 1844627
• 负责人: Bo Sun
• 金额: $ 74.04万
• 依托单位: Oregon State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1844627&HistoricalAwards=false
• 关键词: CAREER; Understand; Multiplexing; Communication; Multicellular

The goal of this research project is to advance our quantitative understanding of information processing in mammalian cells. While much has been learned about single cell, single pathway signaling dynamics, the collective sensory response via highly multiplexed signaling pathways remains poorly understood. A focus of the project is to understand the physics behind the integrated complexity of noise, multiplexing, and communication through a synergy of multiscale investigations. The PI will join will join his institutional and departmental efforts with three personal initiatives. In order to enhance student experience in interdisciplinary education, the PI will develop a hybrid class: BIOPHYSICS Discovery. He will also organize an annual Workshop for Science Storytellers to team up STEM students and liberal art students. The PI will also expand his current outreach programs with more emphasis on first-generation college students and students from low-income families. He will work with colleagues who run a nationally known Physics Education Research group to implement, assess, and disseminate results of education and outreach initiatives.The PI will study the calcium dynamics of endothelium shear-stress sensing and will use advanced microenvironment engineering, statistical analysis, and theoretical modeling. The results will advance the physics of cellular sensor dynamics and have far-reaching impacts in engineering and medicine. In this project the PI will combine both bottom-up and top-down approaches to address the following key questions: What is the molecular mechanism of multiplexed endothelium shear-stress sensing (aim 1)? What is the role of endothelium geometry in regulating the fidelity and resolution of endothelial cell shear sensing (aim 2)? What is the mesoscale endothelium response to altered hemodynamic microenvironment (aim 3)? Answering these questions will significantly advance the knowledge of not only endothelium biology, but also the physics of cell sensory dynamics.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Systems and Synthetic Biology clusters in the Division of Molecular and Cellular Biosciences.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.

该研究项目的目标是促进我们对哺乳动物细胞信息处理的定量理解。虽然已经了解了很多关于单细胞，单通路信号动力学，集体感觉反应通过高度多路信号通路仍然知之甚少。该项目的重点是通过多尺度研究的协同作用，了解噪声、多路复用和通信综合复杂性背后的物理学。PI将加入他的机构和部门的努力与三个个人的倡议。为了提高学生在跨学科教育的经验，PI将开发一个混合类：生物物理发现。他还将组织一个科学讲故事的年度研讨会，让STEM学生和文科学生合作。PI还将扩大他目前的外展计划，更多地关注第一代大学生和低收入家庭的学生。他将与管理一个全国知名的物理教育研究小组的同事合作，实施，评估和传播教育和推广活动的结果。PI将研究内皮剪切应力传感的钙动力学，并将使用先进的微环境工程，统计分析和理论建模。这些结果将推进细胞传感器动力学的物理学，并对工程和医学产生深远的影响。在本项目中，PI将结合联合收割机自下而上和自上而下的方法来解决以下关键问题：多重内皮剪切应力传感的分子机制是什么（目的1）？内皮细胞的几何形状在调节内皮细胞剪切感应的保真度和分辨率中起什么作用（目的2）？中尺度内皮细胞对血流动力学微环境改变的反应是什么（目的3）？解决这些问题不仅将大大提高内皮生物学的知识，也包括细胞感觉动力学物理学。该项目由物理学系的生命系统物理学项目以及分子和细胞生物科学系的系统和合成生物学集群联合支持。该奖项反映了NSF的法定使命，并通过使用评估被认为值得支持基金会的学术价值和更广泛的影响审查标准。

项目成果

Micromechanical remodeling of the extracellular matrix by invading tumors: anisotropy and heterogeneity

侵袭肿瘤对细胞外基质的微机械重塑：各向异性和异质性

• DOI: 10.1039/d2sm01100j
• 发表时间: 2022
• 期刊: Soft Matter
• 影响因子: 3.4
• 作者: Naylor, Austin;Zheng, Yu;Jiao, Yang;Sun, Bo
• 通讯作者: Sun, Bo

Three-dimensional cancer cell migration directed by dual mechanochemical guidance

• DOI: 10.1103/physrevresearch.4.l022007
• 发表时间: 2022-04-12
• 期刊: PHYSICAL REVIEW RESEARCH
• 影响因子: 4.2
• 作者: Esfahani, Pedram;Levine, Herbert;Sun, Bo
• 通讯作者: Sun, Bo

The mechanics and dynamics of cancer cells sensing noisy 3D contact guidance

• DOI: 10.1073/pnas.2024780118
• 发表时间: 2021-03-09
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Kim, Jihan;Cao, Yuansheng;Sun, Bo
• 通讯作者: Sun, Bo