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

CBET-1403887原理研究员耶利米·扎特曼标题：在活跃的、受调节的微环境中解码器官水平的细胞间信号在动物发育过程中对器官大小的调节取决于内部和外部输入：内部因素包括遗传构成和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。对器官大小调控的更多了解可能会使研究人员更好地了解组织和干细胞工程结构中的发育生长。果蝇等基本模型系统中的器官发育为人类生物学提供了宝贵的见解。器官培养系统将被用来测试关于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记者来量化器官内、细胞间的信号。将根据拟议科学研究获得的实况成像数据，通过数字化学习模块加强技术研究，阐明生长和细胞间通讯的原理。研究影响将通过一个学术推广计划来加强，该计划将指导在印第安纳州南本德附近的当地高中进行科学博览会项目的不同人群的高中生。细胞间模式形成、动态平衡和器官生长的协调是器官发育过程中的一个基本生物学过程。尽管有这个基本功能，但整合已知的有丝分裂周期贡献者的统一理论仍然难以捉摸。这项拟议的研究旨在探讨细胞间钙波编码关于上皮细胞大小、分化状态和整体生理的信息的假说。为了验证这一假设，研究人员建议开发新的生物物理方法，在受控的微环境中研究完整的上皮器官中的细胞间钙信号。在基因可修改的模型系统中，将受控微环境与活体成像研究相结合的提议将使系统地研究发育中的上皮细胞对遗传、化学、机械和电干扰的反应。拟议的生物物理方法提供了在以前的努力中未曾见过的实验控制和评估水平。如果成功，对器官内钙波在上皮细胞发育中的功能作用的定量理解将是一个显著的指标，可以翻译为理解高阶生物结构的发育。外源和内在生长调节的统一模型将对生物医学研究产生广泛影响；例如，在干细胞培养和组织工程中引导细胞信号的能力，以及正确调整芯片上器官的功能以进行基础生物医学研究。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。将根据拟议科学研究获得的现场成像数据，开发一个数字化学习模块，说明生长和细胞间通讯的原理。研究影响将通过一个学术推广计划来加强，该计划将指导在当地高中进行科学博览会项目的不同人群的高中生。该奖项由分子和细胞生物科学部门的细胞动力学和功能集群以及化学、生物工程、环境和运输系统部门的生物技术、生化和生物质工程计划共同支持。

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.