NSF PRFB FY 2023: Linking spatial variations in cellular chemical energy turnover to tissue growth in a developing organ

该行动资助了美国国家科学基金会2023财年生物学博士后研究奖学金，研究基因组，环境和表型之间相互作用的生命规则的综合研究。该奖学金支持将以创新方式对生活规则领域作出贡献的研究员的研究和培训。这个项目将研究器官生长和发育过程中能量的利用。这将通过对生长器官中的能量进行成像，然后利用物理学来预测该器官的生长和发育，从而建立一个“生命法则”来实现。这一规律可能对器官研究产生深远的影响，本工作将为理解器官发育提供一个新的视角。这项研究的重点将是肺。更广泛的影响将包括通过普林斯顿大学（普林斯顿学习实验室）为高中生设计的为期8周的年度暑期项目向年轻科学家伸出援助之手，以及对本科生的培训。这个项目探索了一个假设，即驱动组织发育的物理力量与当地的能量生产速度成正比。在早期胚胎鸡和小鼠肺外植体中的测量将化学-能量转换模式与介观组织形态发生联系起来。本项目将(1)利用肺外植体的荧光显微镜测量能量代谢的空间变化，(2)测量肺外植体中组织层的力学特性，(3)从活性物质物理学的角度模拟肺的生长，其驱动力局部与能量产生率成正比。之所以选择胚胎肺作为模型器官，是因为胚胎肺在一个物种内的形态是独特的和刻板的，易于实时成像，并且先前的工作已经表征了肺外植体的形态发生。从鸡蛋中采集的肺将使年轻科学家更容易进行这项研究。本项目包含的培训项目包括高中生暑期项目和大学生子项目。这些实验和模型将是理解器官发生过程中能量学的第一步。这项工作产生的能量代谢和材料特性的空间量化将为从分子水平到发育中的肺的层次结构，再到整个器官规模的细胞能量学与组织生成相关的物理理论提供一个测试平台。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。

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2023, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment, and Phenotypes. The fellowship supports research and training of the fellow that will contribute to the area of Rules of Life in innovative ways. This project will study where energy is used as an organ grows and develops. This will be accomplished by imaging the energy in growing organs and then using physics to predict the growth and development of that organ, thus establishing a “Rule of life.” Such a rule could have far-reaching implications for studying organs, and this work will provide a new perspective for understanding organ development. The organ this study focuses on will be the lung. Broader impacts will include outreach to young scientists through an annual 8 week summer program through Princeton University (The Princeton Learning Laboratory) designed for high school students, as well as training of undergraduate students. This project explores the hypothesis that the physical forces driving tissue development are proportional to the local rate of energy production. Measurements in early embryonic chicken and mouse lung explants will connect patterns of chemical-energy turnover to mesoscopic tissue morphogenesis. The project will (1) use fluorescence microscopy of lung explants to measure spatial variations of energy metabolism, (2) measure the mechanical properties of the tissue layers in the lung explants, and (3) model the growth of the lung from the perspective of active matter physics, with a driving force locally proportional to the rate of energy production. The embryonic lung was chosen as a model organ because the morphology is distinct and stereotyped within a species, easily imaged in real-time, and prior work has characterized the morphogenesis of lung explants. Lungs collected from chicken eggs will make this research easily accessible for young scientists. Training programs incorporated into this project include a high school student summer program and subprojects for university students. These experiments and models will be some of the first work toward understanding energetics in organogenesis. The spatial quantification of energy metabolism and material properties generated by this work will provide a testbed for physical theories that relate cellular energetics to tissue generation from the molecular level, up the hierarchical structure of the developing lung, to the whole-organ scale.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.