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

CBET-1403887 首席研究员 Jeremiah Zartman 标题：在活跃、受调节的微环境中解码器官水平的细胞间信号传导动物发育过程中器官大小的调节取决于内部和外部输入：内部因素包括遗传组成，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尚未完全阐明。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了解组织和干细胞工程结构的发育生长。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记者来量化器官内、细胞间的信号传导。技术研究将通过数字化学习模块得到加强，该模块根据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讯的原理。通过学术推广计划，指导不同群体的高中生在印第安纳州南本德附近的当地高中开展科学博览会项目，研究影响力将得到增强。模式形成、稳态和器官生长的细胞间协调是器官发育过程中的基本生物过程。尽管有这一基本功能，但整合已知有丝分裂周期贡献者的统一理论仍然难以捉摸。这项研究旨在调查细胞间钙波编码有关上皮细胞大小、分化状态和整体生理学信息的假设。为了检验这一假设，研究人员建议开发新的生物物理方法来研究受控微环境内完整上皮器官中的细胞间钙信号传导。所提议的将受控微环境与可基因修改模型系统中的实时成像研究相结合，将能够系统地研究发育中的上皮细胞对遗传、化学、机械和电扰动的反应。所提出的生物物理方法提供了以前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成为一个显着的指标，可转化为理解高级生物结构的发育。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；一个例子是能够在干细胞培养和组织工程中引导细胞信号传导，以及为基础生物医学研究正确缩放芯片上器官的特征。此外，REMChip 将是一个可在其他模型系统中使用的可翻译工具。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数字化学习模块，说明生长和细胞间通讯的原理。通过学术推广计划，指导不同群体的高中生在当地高中开展科学博览会项目，研究影响力将得到增强。 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、生物化学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.