Decoding organ-level intercellular signaling in an active, regulated microenvironment

标题：在一个活跃的、受调节的微环境中解码器官水平的细胞间信号动物发育过程中器官大小的调节取决于内部和外部输入：内部因素包括基因组成，外部因素包括施加的机械应力和周围局部环境的化学成分。内部和外部因素调节器官大小的机制仍未完全阐明。对器官大小调节的更深入了解可能使研究人员能够更好地理解组织和干细胞工程构建中的发育生长。果蝇等基本模型系统的器官发育为人类生物学提供了宝贵的见解。器官培养系统将用于测试内部和外部刺激如何影响器官发育的基本假设。研究人员将使用最新的生物报告来量化器官内、细胞间的信号传导。技术研究将通过一个数字化学习模块来增强，该模块基于从拟议的科学研究中获得的实时成像数据来说明生长和细胞间通信的原理。研究影响将通过一项学术推广计划来增强，该计划将指导在印第安纳州南本德附近的当地高中从事科学展览项目的不同高中生。细胞间模式形成、体内平衡和器官生长的协调是器官发育过程中一个基本的生物学过程。尽管有这个基本功能，一个整合已知有丝分裂周期贡献者的统一理论仍然难以捉摸。本研究旨在探讨细胞间钙波编码上皮细胞大小、分化状态和整体生理信息的假说。为了验证这一假设，研究人员建议开发新的生物物理方法来研究受控微环境下完整上皮器官中的细胞间钙信号。在基因修饰模型系统中，将受控微环境与实时成像研究结合起来，将能够系统地研究发育中的上皮对遗传、化学、机械和电扰动的反应。提出的生物物理方法提供了以前的努力中看不到的实验控制和评估水平。如果成功，对器官内钙波在上皮发育中的功能作用的定量理解将是一个重要的指标，可用于理解高阶生物结构的发育。外源性和内在生长调节的统一模型将对生物医学研究产生广泛的影响；一个例子是在干细胞培养和组织工程中指导细胞信号的能力，以及在基础生物医学研究中正确缩放器官芯片的特征。此外，REMChip将是一个可翻译的工具，可以在其他模型系统中使用。将根据从拟议的科学研究中获得的实时成像数据开发一个说明生长和细胞间通信原理的数字化学习模块。研究影响将通过一项学术拓展计划来增强，该计划将指导在当地高中参加科学展览项目的不同高中生。该奖项由分子和细胞生物科学部的细胞动力学和功能集群以及化学、生物工程、环境和运输系统部的生物技术、生化和生物质工程项目共同支持。

CBET-1403887 Principle Investigator Jeremiah Zartman Title: Decoding organ-level intercellular signaling in an active, regulated microenvironment The regulation of organ size during animal development depends on both internal and external inputs: internal factors include genetic makeup and external factors include applied mechanical stresses and the chemical composition of the surrounding local environment. The mechanisms by which internal and external factors regulate organ size are still not fully elucidated. A greater understanding of organ size regulation may enable researchers to better understand developmental growth in tissue and stem cell engineering constructs. Organ development in basic model systems such as the fruit fly provides valuable insight into human biology. The organ culture system will be used to test basic hypotheses of how internal and external stimuli affect organ development. The researchers will use the latest biological reporters to quantify intra-organ, cell-to-cell signaling. The technical research will be augmented by a digitized learning module illustrating principles of growth and intercellular communication based on the live-imaging data obtained from the proposed scientific study. Research impacts will be enhanced with an academic outreach program mentoring a diverse population of high school students pursuing science fair projects at local high schools near South Bend, IN. Intercellular coordination of pattern formation, homeostasis and organ growth is a fundamental biological process during organ development. Despite this basic function, a unifying theory integrating known contributors to the mitotic cycle remains elusive. The proposed study aims to investigate the hypothesis that intercellular calcium waves encode information on the size, differentiation state and overall physiology of epithelia. To test this hypothesis, the investigators propose developing new biophysical methods to investigate intercellular calcium signaling in intact epithelial organs within a controlled microenvironment. The proposed coupling of a controlled microenvironment with live-imaging studies in a genetically modifiable model system will enable a systematic investigation into the response of developing epithelia to genetic, chemical, mechanical, and electrical perturbations. The proposed biophysical methods provide a level of experimental control and evaluation unseen in previous efforts. If successful, a quantitative understanding of the functional role of intra-organ calcium waves in developing epithelia will be a salient metric that is translatable to understanding development in high-order biological structures. A unified model of exogenous and intrinsic growth regulation will have broad implications for biomedical research; an example is the ability to direct cellular signaling in stem cell culture and tissue engineering as well as correctly scaling the features of organ-on-a-chip for basic biomedical research. Further, the REMChip will be a translatable tool that can be utilized in other model systems. A digitized learning module illustrating principles of growth and intercellular communication will be developed based on the live-imaging data obtained from the proposed scientific study. Research impacts will be enhanced with an academic outreach program mentoring a diverse population of high schools students pursuing science fair projects at local high schools. This award is supported jointly by the Cellular Dynamics and Function Cluster in the Division of Molecular and Cellular Biosciences and by the Biotechnology, Biochemical and Biomass Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems.