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

项目摘要 最近发现锌的波动在人体生理中起着许多调节作用。为 例如，显著的锌部署发生在雌性配子成熟、神经元功能、免疫 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 以及锌在许多细胞模型中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集合如何储存和动员锌来执行功能。这项建议 旨在开发新的定量工具，用于绘制组织中的锌。 我们将通过同时测试 假设锌波动指导小鼠卵巢中原始卵泡的选择性激活。这 假设将使用三种协调和互补的方法来解决：（1）绘制总锌 使用同步加速器X射线荧光显微镜和激光消融感应耦合 等离子体飞行时间质谱;（2）锌响应光声探针的开发;（3） 光声显微镜对卵巢组织锌时空定位研究总的来说，知识 从这个研究项目中获得的信息将揭示锌在生殖健康中的生理学的关键见解， 在此产生的将是有价值的锌在其他人类生理和病理学的研究。 该奖项将支持化学，生殖生物学， 与工程学这些准备工作为独立和多学科的 研究型大学的教授职位。培训活动将针对科学交流、实验室 管理、指导、大学水平的教学和推广。

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.