EAGER: Quantum Imaging for Precise Mapping of Protein Organization during Signaling

EAGER：用于信号传导过程中蛋白质组织精确绘图的量子成像

• 批准号: 2039517
• 负责人: Keith Lidke
• 金额: $ 30万
• 依托单位: University of New Mexico
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2039517&HistoricalAwards=false
• 关键词: EAGER; Quantum; Imaging; Precise; Mapping

Cells have proteins called receptors that bind to signaling molecules and initiate a physiological response. Receptors are generally transmembrane proteins, which bind to signaling molecules outside the cell and subsequently transmit the signal through a sequence of molecular switches to internal signaling pathways. Currently, there are no reliable methods to determine both stoichiometry and precise distances between proteins in a signaling cluster, which is critical for understanding the fundamental mechanisms that control signaling. Quantum-enhanced measurements proposed in this project will allow to approach the physical limits in precision to study protein-protein interactions and determine protein organization during cellular signaling. Undergraduate and graduate students involved in the project will acquire experience in diverse areas including fluorescence microscopy, quantum optics and precision measurements, single-photon detection technologies, cell signaling, and biology.This project will demonstrate quantum-enhanced measurements to realize ultra-precise characterization of protein-protein interactions in intact cells. An image inversion interferometer system for two-point source imaging with high precision will be constructed, and a fast feedback system for center of mass positioning required for the Quantum Imaging technique will be developed. Analyses and estimators that integrate distance measurements and traditional single molecule super resolution microscopy (SMSR) information will be applied to study EGFR and EGFR/Ron clusters on the membrane of intact cells. The proposed work will develop a novel technology that merges quantum-enhanced imaging techniques with state-of-the art SMSR, to provide a 10-fold resolution enhancement for precise imaging of proteins in signaling clusters with approximately 1 nm resolution. This project is supported by the Biological Sciences Directorate.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.

细胞具有称为受体的蛋白质，可与信号分子结合并引发生理反应。受体通常是跨膜蛋白，它们与细胞外的信号分子结合，然后通过一系列分子开关将信号传输到内部信号通路。当前，没有可靠的方法来确定信号群集中蛋白质之间的化学计量和精确距离，这对于理解控制信号传导的基本机制至关重要。该项目提出的量子增强测量值将允许在精确的物理极限上研究蛋白质 - 蛋白质相互作用并确定细胞信号过程中蛋白质组织。 参与该项目的本科生和研究生将获得各种领域的经验，包括荧光显微镜，量子光学和精确测量，单光子检测技术，细胞信号传导和生物学。该项目将证明量子增强的测量值以实现蛋白质相互作用的完整细胞中的超精确表征。将构建用于具有高精度的两点源成像的图像反转干涉仪系统，并将开发量子成像技术所需的质量定位中心的快速反馈系统。 将整合距离测量值和传统单分子超级分辨率显微镜（SMSR）信息的分析和估计器将应用于完整细胞膜上的EGFR和EGFR/RON簇。拟议的工作将开发一种新型技术，该技术将量子增强的成像技术与最先进的SMSR合并，以提供10倍分辨率的增强，以在具有大约1 nm分辨率的信号簇中精确的蛋白质成像。该项目得到了生物科学局的支持。该奖项反映了NSF的法定使命，并被认为是值得通过基金会的知识分子优点和更广泛影响的评论标准来评估的。