Growth and size in living matter

生命系统通常具有特征尺寸：小鼠不会长得比大象大，健康的细菌通常会选择在达到适当长度时分裂，而不是永远继续伸长。 至少在某些情况下，这些尺寸似乎是以相当高的精度指定的。 例如，从人类四肢到果蝇翅膀的器官在同一动物的左右器官之间表现出约1%的大小不对称性，并且在适当的条件下，分裂时细菌长度的变异系数约为10%。 我们对这些数字的来源知之甚少。 生物体内的哪种噪音或变异性最终对尺寸误差贡献最大？ 机翼尺寸相差1%是否令人惊讶地好，接近物理学基本定律可能的极限，或者很容易想象如何使差异更小？ 这个项目使用物理科学的方法来开发回答这些问题所需的基本理论框架。 研究人员将进一步与实验室合作，完善他们的想法，并将其应用于特定的生命系统。该项目还将为各级学生提供在跨学科团队中进行研究的机会，特别是首席研究员将与密歇根大学的M-STEM学院合作，招募多样化的本科生加入项目团队。 主要研究者还将开发辅导练习，基于他在生物物理学的研究，为密歇根大学生命科学专业学生的物理学入门课程序列。技术总结该提案资助理论和计算研究，包括与几个实验组的合作，研究统计和非线性物理的增长，活跃的系统，如那些在生活物质中发现的。 一个统一的问题是，噪声和波动如何影响生长，并限制达到给定最终尺寸的精度。 研究人员将在多个尺度和多个模型系统中探索这些问题。 特别是，它们将：（1）检查随机生长和生长停滞的集总、无空间模型，并应用于（A）细胞和器官的大小分布;（B）果蝇对侧翅膀之间的大小协调;（C）斑马鱼体节发生过程中对侧体节之间的大小协调。 形式上，这些模型最初将采取两个变量的首次通过问题的形式，实际和估计的大小。 扩展将包括允许存在各种形式的相关和非白噪声。 (2)研究基于细胞的组织空间分辨生长模型。 这里的目标将是确定如何在细胞大小的相关性跨组织可以用来推断组织大小的调节机制，并了解是什么限制了细胞大小的一致性在粘性组织。 特别是，研究人员将比较和对比生长和增殖停滞同时发生的模型与分裂停止后细胞大小调整和校正发生的模型。 理论预测将与果蝇翅膀和背蛹背背的观察结果进行比较。该项目将把教育与跨学科研究相结合，同时支持多样化的学生群体，丰富课堂教学，并加强努力，以维持密歇根大学有凝聚力的定量生物学社区。它将使各级学生有机会在一个团队中进行研究，他们将与来自生物和物理科学的同事密切合作，并将支持一名研究生的国际研究经验。 首席研究员将与密歇根大学的M-STEM学院合作，让不同群体的本科生在大学生涯的早期参与研究;这种参与已被证明可以提高科学和工程领域历史上代表性不足的学生的保留率。 该项目进一步支持工作室练习的持续发展，将生物学相关的例子纳入生命科学专业的入门物理课程序列，并支持首席研究员在密歇根大学组织跨学科定量生物学研讨会和期刊俱乐部系列的工作。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识产权进行评估来支持。优点和更广泛的影响审查标准。

NON-TECHNICAL SUMMARY Living systems usually have characteristic sizes: Mice do not grow larger than elephants, and healthy bacteria generally choose to divide when they reach the appropriate length rather than to continue elongating forever. In at least some cases, these sizes appear to be specified with fairly high precision. For example, organs from human limbs to fruit fly wings exhibit size asymmetry between the left and right organ in the same animal of about 1%, and in appropriate conditions the coefficient of variation of bacterial length at division is around 10%. Very little is known about where these numbers come from. What sorts of noise or variability inside the living organism ultimately contribute the most to size errors? Is a 1% difference in wing sizes surprisingly good, close to the limits of what is possible given basic laws of physics, or would it be easy to imagine how the difference could be made even smaller? This project with use methods from the physical sciences to develop the basic theoretical framework needed to answer questions like these. The investigators will further collaborate with experimental labs to refine their ideas and apply them to specific living systems.The project will also give students at all levels an opportunity to pursue research in an interdisciplinary team; in particular, the principal investigator will work with the University of Michigan’s M-STEM Academies to recruit a diverse group of undergraduate students to the project team. The principal investigator will also develop tutorial exercises, based on his research in biological physics, for the introductory physics course sequence for life science students at the University of Michigan.TECHNICAL SUMMARYThis proposal funds theoretical and computational research, including collaborations with several experimental groups, to study the statistical and nonlinear physics of growing, active systems like those found in living matter. A unifying question is how noise and fluctuations affect growth and limit the precision with which a given final size can be reached. The investigators will explore these issues at multiple scales and in multiple model systems. In particular, they will: (1) Examine lumped, space-free models of stochastic growth and growth arrest, with applications to (A) size distributions of cells and organs; (B) size coordination between contralateral wings in the fruit fly Drosophila melanogaster; and (C) size coordination between contralateral somites during zebrafish somitogenesis. Formally, these models will initially take the form of first passage problems in two variables, an actual and an estimated size. Extensions will include allowing for the presence of various forms of correlated and non-white noise. (2) Study cell-based models of spatially resolved growth in tissues. Goals here will be to determine how correlations in cell size across tissues can be used to draw inferences about mechanisms of tissue size regulation and to understand what limits the uniformity of cell size in cohesive tissues. In particular, the investigators will compare and contrast models in which growth and proliferation arrest occur simultaneously with models where cell size adjustment and correction occurs after division has ceased. Theoretical predictions will be compared to observations in Drosophila wings and dorsal pupal notum.This project will integrate education with interdisciplinary research while supporting a diverse student body, enriching classroom instruction, and reinforcing efforts to sustain a cohesive quantitative biology community at the University of Michigan. It will give students at all levels an opportunity to pursue research in a team where they will work closely with colleagues from both the biological and the physical sciences and will support international research experiences for one graduate student. The principal investigator will work with the University of Michigan’s M-STEM Academy to involve a diverse group of undergraduates in research early in their college careers; such involvement has been shown to improve retention of students from historically under-represented groups in science and engineering fields. The project further supports the continued development of studio exercises incorporating biologically relevant examples for the introductory physics course sequence for life sciences majors and the principal investigator’s work in organizing an interdisciplinary quantitative biology seminar and journal club series at the University of Michigan.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.