CAREER: Symmetry and Geometry in Biological Active Matter

在这个职业项目中，PI旨在解决的基本问题是：Rho GTP酶形成时空模式的基本原理是什么，以及它们在调节细胞皮质和细胞变形的机制中起什么作用？由细胞皮质的机械(动态)变形和Rho GTP酶的化学模式引起的细胞形状变化和细胞质流动之间的反馈是什么？为了解决这些问题，PI将结合实验和理论来确定化学模式和机械细胞变形之间相互作用的基本原理，从而为全面了解动物细胞中机械化学模式的动力学奠定基础。揭示生物系统中机械力-化学结构形成的原理也将促进新的智能材料和软机器人技术。拟议的研究活动将与物理和生物相结合的教学活动紧密结合在一起。(I)国际学生联合会将继续通过麻省理工学院的研究科学研究所指导高中生。(Ii)作为麻省理工学院暑期研究计划(MSRP)的教师导师，PI将继续指导和吸引未被充分代表的学生(少数族裔、STEM中的女性或社会经济地位较低的学生)来麻省理工学院获得重要的研究经验并探索在麻省理工学院接受博士教育的可能性。该项目将结合新颖的实验技术、理论和数学建模来阐明活跃的力学和细胞几何如何在与化学反应相结合时产生强大的机械力-化学反应模式。所有动物细胞共有的重要生命过程，如胞质分裂和细胞迁移，都需要化学蛋白质模式和细胞形状的机械变形之间的相互作用和协调。两者的核心都是活跃的过程，由高度保守的Rho GTP酶家族和肌球蛋白马达消耗ATP的作用驱动和调节。在这个项目的过程中，PI将构建、实施和实验验证一个全面的理论模型，以量化和理解Rho GTP酶的化学模式、机械细胞变形和细胞质流动之间的机械力化学耦合机制。由于海星卵母细胞是一个成熟的系统，具有很高的实验可及性，因此将被用作研究体内发育过程中机械力化学模式的生物模型系统。将开发一种基于近红外荧光单壁碳纳米管的新型成像平台，以生成开发过程中大脑皮质动力学和力学的高分辨率地图。它将与信号蛋白定位的体内成像以及生化、生物物理和光遗传操作相结合。由于Rho GTP酶无处不在，尤其与细胞的动态空间结构有关，研究应该揭示机械变形和生化模式形成相互作用的普遍原理。该项目由物理部的生命系统物理学计划和分子和细胞生物科学部的细胞动力学和功能簇共同支持。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。

The fundamental questions that the PI aims to address in this CAREER project are: What are the principles underlying the formation of spatio-temporal patterns of Rho GTPases, and what is their functional role in regulating the mechanics of the cell cortex and cell deformation? What is the feedback between cell shape changes and cytoplasmic flow induced by mechanical (dynamic) deformation of the cell cortex and the chemical pattern of Rho GTPases? To address these questions, the PI will combine experiment and theory to identify the fundamental principles underlying this interplay between chemical patterns and mechanical cell deformations and thereby to lay the foundation for a comprehensive understanding of the dynamics of mechano-chemical patterns in animal cells. Uncovering the principles of mechano-chemical structure formation in biological systems will also facilitate new smart materials and soft robotics technology. The proposed research activities will be closely integrated with teaching activities at the interface of physics and biology. (i) The PI will continue to mentor high school students through the Research Science Institute at MIT. (ii) As a faculty mentor for the MIT Summer Research Program (MSRP) General, the PI will continue to mentor and to attract underrepresented students (minorities, women in STEM, or students with low socioeconomic status) to MIT to gain significant research experience and explore the possibility of doctoral education at MIT.This project will combine novel experimental techniques, theory and mathematical modeling to elucidate how active mechanics and cell geometry, when coupled to chemical reactions, give rise to robust mechano-chemical patterns. Important life processes common to all animal cells such as cytokinesis and cellular migration require the interplay and coordination between chemical protein patterns and mechanical deformation of the cell shape. At the heart of both are active processes, driven and regulated by the highly conserved Rho family of GTPases and the action of myosin motors consuming ATP. Over the course of this project, the PI will construct, implement and experimentally validate a comprehensive theoretical model to quantify and to understand the mechanisms of mechano-chemical coupling between chemical patterns of Rho GTPases, mechanical cell deformations, and cytoplasmic flow. Starfish oocytes will be used as a biological model system to study mechano-chemical patterns during development in vivo, as they are a well-established system with a high degree of experimental accessibility. A novel imaging platform based on near-IR fluorescent single-walled carbon nanotubes will be developed to generate high resolution maps of cortex dynamics and mechanics during development. It will be combined with in vivo imaging of signaling protein localization, as well as biochemical, biophysical and optogenetic manipulations. As Rho GTPases are ubiquitous and in particular associated to the dynamic spatial structuring of cells, the investigations should reveal universal principles for the interplay of mechanical deformations and biochemical pattern formation.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Cellular Dynammics and Function Cluster 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.