IDBR: TYPE A - Development of an In situ Single-cell Mass Spectrometer for Mapping Small-molecule Expression in the Developing Embryo

IDBR：A 型 - 开发用于绘制发育中胚胎中小分子表达图谱的原位单细胞质谱仪

• 批准号: 1826932
• 负责人: Peter Nemes
• 金额: $ 14.32万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1826932&HistoricalAwards=false
• 关键词: IDBR; TYPE; Development; situ; Single

An award is made to the George Washington University to develop a device that will be able to measure the production of broad types of biomolecules in multiple, individual cells of the developing embryo. This project will enhance education by integrating biology and chemistry, and provide new investigative tools to raise creative research opportunities in basic and applied research. Development of the single-cell mass spectrometer will require regular interactions between analytical chemists, biologists, mass spectrometrists, and curators of data repositories, essentially creating an interdisciplinary environment for students and researchers to accomplish training beyond the classical curriculum in these disciplines. By demonstrating the device at the George Washington University and discussing its design, performance, and use at national conferences and publications, this work will broaden scientific literacy and inform of the availability of the device to a broader base of users. Data resulting from measurements on the production of biomolecules during embryogenesis will be disseminated in publicly accessible data repositories, providing a larger number of users with access to facilitate research and education in cell and developmental biology and neuroscience. Notably, the combination of these scientific and outreach elements, including participation of local high-school students in the project, will enhance research and education at the interface of biology, instrument development, and analytical chemistry, providing interdisciplinary solutions to current and future challenges in science and education. Characterization of biomolecular expression in single cells of the embryo will provide new insights into basic biochemical mechanisms that orchestrate embryonic development, the complex suite of processes by which a fertilized egg gives rise to an entire, fully functioning organism such as the frog, fish, or human. Although it has been technologically feasible to measure genes and transcripts in single embryonic cells, a lack of analytical technology has so far hindered the characterization of proteins, peptides, and metabolites in single embryonic cells. This project will provide one such technological innovation, a single-cell mass spectrometer, by combining traditional tools in cell and developmental biology and neuroscience with next-generation instrumentation from bioanalytical chemistry. Specifically, optical microscopy, microinjection, microcapillary electrophoresis, and nanoelectrospray ionization will be adapted to high-resolution tandem mass spectrometry to determine the production of biomolecules, proteins to metabolites, in multiple cells of the embryo using the frog Xenopus laevis and zebrafish as models. The instrument will be developed in collaboration with leading mass spectrometric industry, biologists, and students, and will be tested by biologists and students working with these important developmental models.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

乔治华盛顿大学获得了一项奖项，用于开发一种设备，该设备能够测量发育中胚胎的多个单个细胞中多种生物分子的产生。该项目将通过整合生物学和化学来加强教育，并提供新的研究工具，以增加基础和应用研究的创造性研究机会。单细胞质谱仪的开发需要分析化学家、生物学家、质谱学家和数据存储库管理者之间的定期互动，从本质上为学生和研究人员创造一个跨学科环境，以完成这些学科经典课程之外的培训。通过在乔治华盛顿大学展示该设备并在全国会议和出版物上讨论其设计、性能和使用，这项工作将扩大科学素养并向更广泛的用户群通报该设备的可用性。胚胎发生过程中生物分子产生的测量数据将在可公开访问的数据存储库中传播，为更多用户提供便利，以促进细胞和发育生物学以及神经科学的研究和教育。值得注意的是，这些科学和外展元素的结合，包括当地高中生参与该项目，将加强生物学、仪器开发和分析化学领域的研究和教育，为当前和未来的挑战提供跨学科解决方案。科学和教育。胚胎单细胞中生物分子表达的表征将为了解协调胚胎发育的基本生化机制提供新的见解，胚胎发育是受精卵产生完整的、功能齐全的生物体（如青蛙、鱼或动物）的一系列复杂过程。人类。尽管测量单个胚胎细胞中的基因和转录本在技术上是可行的，但迄今为止分析技术的缺乏阻碍了单个胚胎细胞中蛋白质、肽和代谢物的表征。该项目将通过将细胞和发育生物学以及神经科学的传统工具与生物分析化学的下一代仪器相结合，提供这样一种技术创新，即单细胞质谱仪。具体来说，光学显微镜、显微注射、微毛细管电泳和纳电喷雾电离将适应高分辨率串联质谱法，以青蛙非洲爪蟾和斑马鱼为模型，确定胚胎多个细胞中生物分子、蛋白质和代谢物的产生。该仪器将与领先的质谱行业、生物学家和学生合作开发，并将由使用这些重要发展模型的生物学家和学生进行测试。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准。