Vibrational Spectroscopic Imaging to Unveil Hidden Signatures in Living Systems

振动光谱成像揭示生命系统中隐藏的特征

• 批准号: 10660979
• 负责人: Ji-Xin Cheng
• 金额: $ 57.75万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660979
• 关键词: Action Potentials; Antimicrobial Resistance; Anus; Biological; Biology; Cells; Cellular Metabolic Process; Chemicals; Chemistry; Collaborations; Communicable Diseases; Development; Diagnosis; Disseminated Malignant Neoplasm; Engineering; Entrepreneurship; Exposure to; Goals; Image; Imaging technology; Label; Life; Malignant Neoplasms; Maps; Medicine; Membrane; Metabolic; Metabolism; Microscopy; Mission; Molecular Profiling; Neurons; Optics; Organism; Penetration; Pharmacotherapy; Photons; Physics; Property; Research; Resolution; Science; Speed; Stress; Technology; Time; Tissues; cancer cell; cell behavior; chromophore; detection sensitivity; drug resistant bacteria; human disease; imaging platform; in vivo; invention; microorganism; molecular assembly/self assembly; neural; photolysis; programs; response; single molecule; spectroscopic imaging; stem cells; stemness; tumor progression; voltage

Project Summary A central theme of research in the Cheng group is focused on basic understanding of how biomolecules and/or molecular assemblies function in space and time to drive life. For example, how does the membrane respond to the action potential in neurons? How is the metabolism remodelled during cell development or cancer progression? What happens to the chemistry inside a microorganism when exposed to a drug treatment? Answering these questions has broad implications for diagnosing and treating conditions ranging from infectious diseases to metastatic cancers. Towards this mission, Cheng and his team invent and apply highly sensitive chemical imaging technologies that are able to unveil hidden signatures in various living systems. The eventual goal is to enable molecule-based precision diagnosis and/or treatment of human diseases. The Cheng team further harnesses and manipulates the unique properties of photons to modulate the behaviour of cells. Two focused projects are photolysis of chromophores to eradicate drug-resistant bacteria and optoacoustic modulation of neural tissues at ultrahigh spatial precision. Overall, with integrated expertise in engineering, physics, chemistry, biology, medicine and entrepreneurship, the research team is devoted to three integrated thrusts: (1) Inventing label-free optical modulation and spectroscopic imaging technologies and pushing their physical limits; (2) Discovering molecular signatures that define cellular state and functions; (3) Converting label- free technologies and biological discoveries into molecule-based precision diagnosis and treatments. During the past 5 years (2013 to 2018), research by Cheng and co-workers has pushed the boundary of vibrational spectroscopic imaging in terms of speed, spectral bandwidth, imaging depth, and detection sensitivity (for a review, Science, 2015, 350: aaa8870). In parallel, via collaborations, Cheng and co-workers discovered significant metabolic signatures defining cancer aggressiveness (Cell Metabolism 2014), cancer cell stemness (Cell Stem Cell 2017), and antimicrobial resistance (Anal Chem 2017), as well as a spectroscopic indicator of membrane voltage in neurons (JPC Lett 2017). The overarching goal of this MIRA proposal is to further push the boundary of nonlinear vibrational spectroscopic imaging platforms in order to unveil the signatures that underlie initiation or progression of human diseases by “watching the orchestra of molecules” in real space and time inside a living system. Cheng and co-workers will pursue this goal by advancing the capability of two complimentary vibrational imaging platforms, namely multiplex stimulated Raman scattering microscopy and infrared photothermal microscopy both invented in the Cheng lab, to reach single-molecule detection sensitivity, 100-nm spatial resolution, volumetric mapping at high speed, and deep-tissue penetration. As a focused application, the team will deploy the developed technologies to advance the basic understanding of how a biological cell reprograms its metabolism during development in vivo or in response to a stress.

项目摘要 Cheng Group研究的一个核心主题集中于对生物分子的基本了解 和/或分子组件在驱动生命的时空中起作用。例如，膜如何 回应神经元的动作潜力？在细胞发育或癌症过程中，新陈代谢如何重塑 进展？暴露于药物治疗时，微生物中的化学反应会怎样？ 回答这些问题对诊断和治疗状况的影响很大。 转移性癌症的疾病。为了执行此任务，Cheng和他的团队发明并应用高度敏感 能够在各种生活系统中推出隐藏特征的化学成像技术。最终 目标是实现基于分子的精度诊断和/或人类疾病治疗。郑队 进一步利用并操纵照片的独特特性，以调节细胞的行为。二 专注的项目是发色团对放射性药物耐药细菌和光声的光解 在超高空间精度下对神经检查的调节。总体而言，具有工程专业知识， 物理，化学，生物学，医学和企业家精神，研究团队专门针对三个综合 推力：（1）发明无标签的光学调制和光谱成像技术并推动其推动 物理极限； （2）发现定义细胞状态和功能的分子特征； （3）转换标签 - 基于分子的精确诊断和治疗的自由技术和生物学发现。 在过去的5年（2013年至2018年）中，Cheng和同事的研究推动了边界 振动光谱成像在速度，光谱带宽，成像深度和检测灵敏度方面 （有关评论，科学，2015，350：AAA8870）。同时，通过合作，郑和同事发现了 定义癌症攻击性的重要代谢特征（细胞代谢2014），癌细胞的干性 （细胞干细胞2017）和抗菌耐药性（肛门化学2017），以及光谱指标 神经元中的膜电压（JPC Lett 2017）。这个Mira提议的总体目标是进一步推动 非线性振动光谱成像平台的边界，以揭露 通过在真实空间中“观看分子乐团”和 生活系统内的时间。 Cheng及其同事将通过提高两个的能力来追求这一目标 免费的振动成像平台，即多重刺激的拉曼散射显微镜和 红外光热显微镜均在Cheng Lab中发明，以达到单分子检测灵敏度， 100 nm的空间分辨率，高速的体积映射和深度组织渗透。作为专注的 应用程序，团队将部署开发的技术，以促进对如何 生物细胞在体内或响应压力的过程中重新编程其代谢。

项目成果

Nanoscale bond-selective imaging by computational fusion of atomic force microscopy and coherent anti-Stokes Raman scattering microscopy.

• DOI: 10.1039/d3an00662j
• 发表时间: 2023-06
• 期刊: The Analyst
• 作者: Le Wang;Ji-Xin Cheng

Visualization of a Limonene Synthesis Metabolon Inside Living Bacteria by Hyperspectral SRS Microscopy.

• DOI: 10.1002/advs.202203887
• 发表时间: 2022-11
• 期刊: ADVANCED SCIENCE
• 影响因子: 15.1
• 作者: Zhang, Jing;Shin, Jonghyeon;Tague, Nathan;Lin, Haonan;Zhang, Meng;Ge, Xiaowei;Wong, Wilson;Dunlop, Mary J.;Cheng, Ji-Xin
• 通讯作者: Cheng, Ji-Xin

Fluorescence-Detected Mid-Infrared Photothermal Microscopy.

• DOI: 10.1021/jacs.1c03642
• 发表时间: 2021-08-04
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Zhang Y;Zong H;Zong C;Tan Y;Zhang M;Zhan Y;Cheng JX
• 通讯作者: Cheng JX

Vibrational Spectroscopic Detection of a Single Virus by Mid-Infrared Photothermal Microscopy.

• DOI: 10.1021/acs.analchem.0c05333
• 发表时间: 2021-03-02
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Zhang, Yi;Yurdakul, Celalettin;Devaux, Alexander J.;Wang, Le;Xu, Xiaoji G.;Connor, John H.;Unlu, M. Selim;Cheng, Ji-Xin
• 通讯作者: Cheng, Ji-Xin

Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins.

• DOI: 10.3389/fneur.2020.579434
• 发表时间: 2020
• 期刊: Frontiers in neurology
• 影响因子: 3.4
• 作者: Jiang L;Zhao J;Cheng JX;Wolozin B
• 通讯作者: Wolozin B