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

这个研究项目的目标是促进我们对哺乳动物细胞中信息处理的定量理解。虽然对单细胞、单通路信号动力学已经了解了很多，但通过高度多路信号通路的集体感觉反应仍然知之甚少。该项目的一个重点是通过多尺度研究的协同作用来理解噪声、多路复用和通信综合复杂性背后的物理原理。私家侦探将加入他的机构和部门的工作，以三项个人倡议。为了提高学生在跨学科教育中的经验，PI将开发一门混合课程：生物物理学发现。他还将组织一年一度的科学故事讲述者研讨会，让STEM学生和文科学生组成团队。PI还将扩大目前的外展项目，将重点放在第一代大学生和低收入家庭的学生身上。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。研究结果将推动细胞传感器动力学的物理学发展，并在工程和医学领域产生深远的影响。在这个项目中，PI将结合自下而上和自上而下的方法来解决以下关键问题：多路内皮剪切应力传感的分子机制是什么（目标1）？内皮几何结构在调节内皮细胞剪切感知的保真度和分辨率中的作用是什么（目的2）？什么是中尺度内皮对改变的血流动力学微环境的反应（目的3）？回答这些问题将显著推进不仅内皮生物学的知识，也细胞感觉动力学的物理。该项目由物理系的生命系统物理学项目和分子与细胞生物科学系的系统与合成生物学集群共同支持。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 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.