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

这项行动资助了2023财年的NSF生物学博士后研究奖学金，综合研究调查了基因组，环境和表型之间的生命管理相互作用的规则。该研究金支持研究员的研究和培训，以创新的方式为生活规则领域做出贡献。该项目将研究在器官生长和发育过程中能量的使用情况。这将通过成像生长器官中的能量来实现，然后使用物理学来预测该器官的生长和发育，从而建立“生命规则”。这样的规则可能对器官的研究产生深远的影响，这项工作将为理解器官发育提供新的视角。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周的年度暑期课程，向年轻科学家进行宣传，以及对本科生进行培训。该项目探讨了驱动组织发育的物理力与局部能量产生率成比例的假设。在早期胚胎鸡和小鼠肺外植体的测量将连接模式的化学能量周转介观组织形态发生。该项目将（1）使用肺外植体的荧光显微镜来测量能量代谢的空间变化，（2）测量肺外植体中组织层的机械特性，以及（3）从活性物质物理学的角度模拟肺的生长，驱动力与能量产生速率成比例。选择胚胎肺作为模型器官，因为形态在物种内是独特的和定型的，容易实时成像，并且先前的工作已经表征了肺外植体的形态发生。从鸡蛋中收集的肺将使年轻科学家很容易进行这项研究。纳入该项目的培训方案包括高中生暑期方案和大学生分项目。这些实验和模型将是理解器官发生中能量学的第一批工作。这项工作所产生的能量代谢和材料特性的空间量化将为物理理论提供一个试验平台，该理论将细胞能量学与组织生成从分子水平联系起来，沿着发育中的肺的层次结构，整个-该奖项反映了NSF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进行评估，被认为值得支持的搜索.

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.