Tissue-Based Metal Imaging Tools and Their Application Towards Spatiotemporal Mapping of Zinc Fluxes in Ovaries

基于组织的金属成像工具及其在卵巢锌通量时空绘图中的应用

基本信息

批准号：
10226867
负责人：
David Zhi Hong Zee
金额：
$ 7.11万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10226867
关键词：
Ablation Address Award Beds Binding Biological Biology Cell model Cells Chemistry Communication Communities Complex Coupled Data Development Educational process of instructing Embryo Engineering Estrous Cycle Event Exhibits Exocytosis Female Fertilization Fluorescence Microscopy Fluorescent Probes Foundations Germ Cells Goals Gonadotropins Growth Human Image Imaging Device Imaging Techniques Immune response Ions Knowledge Lasers Ligands Light Maps Measures Meiosis Mentorship Metals Microscopy Molecular Molecular Probes Mus Neurons Oocytes Oogonia Optics Organ Organism Ovarian Ovarian Tissue Ovary Pathology Penetration Physiology Plasma Play Preparation Primordial Follicle Reproductive Biology Reproductive Health Research Research Personnel Research Project Grants Research Support Resolution Roentgen Rays Role Sampling Slice Synchrotrons Technology Testing Tissues Training Training Activity Ultrasonography Universities Vesicle Zinc base cellular imaging college design egg fluorescence imaging imaging modality in vivo insight insulin secretion interest light scattering microscopic imaging multidisciplinary outreach photoacoustic imaging ratiometric reproductive response small molecule spatiotemporal time of flight mass spectrometry tool uptake zygote

项目摘要

PROJECT SUMMARY Zinc fluctuations have recently been discovered to play a number of regulatory roles in human physiology. For example, significant zinc deployments occur during female gamete maturation, neuron function, immune response, and insulin secretion. Metal imaging techniques at the single-cell level have established the cellular and subcellular distribution and fluxes of zinc in a number of cellular models. However, few imaging tools are able to measure how ensembles of cells and organs store and mobilize zinc to carry out function. This proposal aims to develop new quantitative tools for mapping zinc in tissue. We will test the utility of new zinc imaging tools developed in this proposal by simultaneously testing the hypothesis that zinc fluctuations direct the selective activation of primordial follicles in the murine ovary. This hypothesis will be addressed using three coordinated and complementary approaches: (1) mapping total zinc levels in mouse ovaries using synchrotron X-ray fluorescence microscopy and laser ablation inductively coupled plasma time-of-flight mass spectrometry; (2) the development of zinc-responsive photoacoustic probes; (3) spatiotemporal mapping of zinc in ovarian tissue with photoacoustic microscopy. Taken together, the knowledge gained from this research project will reveal key insight into zinc physiology in reproductive health, and the tools produced here will be valuable for the study of zinc in other human physiologies and pathologies. This award will support research and professional training at the interface of chemistry, reproductive biology, and engineering. These preparations provide a strong foundation for an independent and multidisciplinary professorship at a research university. Training activities will target progress in scientific communication, lab management, mentorship, college-level teaching, and outreach.

项目概要最近发现锌的波动在人体生理学中发挥着多种调节作用。为了例如，在雌性配子成熟、神经元功能、免疫过程中发生显着的锌部署反应和胰岛素分泌。单细胞水平的金属成像技术已经建立了细胞以及许多细胞模型中锌的亚细胞分布和通量。然而，很少有成像工具能够测量细胞和器官的整体如何储存和动员锌来执行功能。这个提议旨在开发新的定量工具来绘制组织中的锌图谱。我们将通过同时测试本提案中开发的新型锌成像工具的实用性假设锌的波动指导小鼠卵巢中原始卵泡的选择性激活。这将使用三种协调和互补的方法来解决假设：（1）绘制总锌量图使用同步加速器 X 射线荧光显微镜和激光烧蚀感应耦合技术测定小鼠卵巢中的水平等离子体飞行时间质谱分析； (2)锌响应光声探针的研制； (3) 用光声显微镜绘制卵巢组织中锌的时空图谱。综合起来，知识从该研究项目中获得的成果将揭示生殖健康中锌生理学的重要见解，以及工具这里生产的锌对于研究其他人类生理和病理学中的锌具有重要价值。该奖项将支持化学、生殖生物学、和工程。这些准备工作为独立和多学科的研究奠定了坚实的基础。一所研究型大学的教授。培训活动将针对科学传播、实验室方面的进展管理、指导、大学教学和外展。