EAGER: Detection Of In Vivo Corticosterone In Mice Using Cophmore Engineering And Fluorescent Carbon Nanotube Sensors

肾上腺产生的类固醇激素是心理应激的重要生物标志物。它们参与脂肪和糖的新陈代谢，调节免疫系统和大脑的认知过程。尽管在日常生活中明显需要表征这些类固醇的动态变化，但在体内检测这些重要激素的方法方面进展甚微。麻省理工学院(MIT)的Michael Stro博士的研究团队将以他们最近开发的名为电晕相分子识别(CoPhMoRe)的平台技术为基础，创建新型传感器，用于在体内长期监测特定的类固醇激素皮质酮，这是一种啮齿动物的类固醇激素。如果成功，从血液、大脑和其他组织中连续、快速地检测皮质酮将成为现实。最初，用于皮质酮的纳米级荧光传感器将被放置在感兴趣区域附近的小鼠体内，方法是将它们注入血流，将它们结合并植入生物相容的水凝胶颗粒中，或者将它们固定在波导型探针上。一旦内化，传感器将通过非侵入性光线激活来确定局部皮质酮浓度。通过用光测量传感器响应，可以快速(1秒)和连续(1年)监测皮质酮浓度。这种新的传感器将为这种荷尔蒙的动态和相关的生理过程提供全新的见解，并为进一步开发皮质醇传感器奠定基础，皮质醇是人类的一种相关应激激素。这项技术将使人们能够详细了解类固醇激素在健康和疾病组织中的作用。了解压力反应系统的动态功能对于开发涉及压力调节的许多社会和健康问题的解决方案至关重要。利用啮齿动物模型系统研究体内皮质酮传感器的发展，将对应激在认知功能中的作用的基础研究和应激相关疾病的临床治疗研究具有革命性意义。为人类皮质醇检测的最终发展开发非侵入性纳米级传感器的经济和社会效益是巨大的。此外，这个项目将提供一个在纳米尺度上理解分子识别的机会，作为学生的教学辅助工具。使用带有改进的光学和近红外探测器的传统显微镜，学生能够在单分子水平上研究CoPhMoRe，以及学习体内研究所需的技术。麻省理工学院的斯特拉诺实验室在与本科生和少数族裔合作和出版方面有着良好的记录；这笔赠款将通过支持一名女性博士后来继续这些努力。

Steroid hormones produced by the adrenal gland are important biomarkers for psychological stress. They are involved in fat and sugar metabolism, modulation of the immune system and cognitive processes in the brain. Despite the obvious need to characterize the dynamic changes in these steroids throughout daily life, there has been little progress towards a method of in vivo detection of these important hormones. Dr. Michael Strano's research team at the Massachusetts Institute of Technology (MIT) will build upon their recently developed platform technique called Corona Phase Molecular Recognition (CoPhMoRe) to create novel sensors for long-term in vivo monitoring of a specific steroid hormone, corticosterone, a steroid hormone in rodents. If successful, continuous and fast detection of corticosterone from the blood, the brain, and other tissues will become a reality. Initially, nanoscale fluorescent sensors for corticosterone will be placed in mice near the region of interest either by injecting them into the blood stream, incorporating and implanting them in biocompatible hydrogel particles or immobilizing them on waveguide probes. Once internalized the sensors will determine local corticosterone concentrations through activation by a non-invasive light. Measuring sensor responses with light enables fast ( 1 second) and continuous (1 year) monitoring of corticosterone concentrations. This new sensor will provide completely new insights into the dynamics of this hormone and related physiological processes and form the foundation for further developing the sensor for cortisol, a related stress hormone in humans. This technology will enable a detailed understanding of the role of steroid hormones in the healthy, as well as diseased, organism.Understanding the dynamic function of the stress response system is critical for developing solutions for many social and health problems that involve stress regulation. The development of an in vivo corticosterone sensor for investigation using rodent model system will be transformative for both the basic research in the role of stress in cognitive function and clinical research on treatment of illness associated with stress. The economic and societal benefits of developing noninvasive nanoscale sensors for the ultimate development of cortisol detection in humans are enormous. In addition, this project will provide an opportunity to understand molecular recognition at the nanometer scale as a teaching aid to students. Using conventional microscopy with modified optics and near infrared detectors, students are able to study CoPhMoRe at the single molecule level as well as to learn the techniques needed for in vivo research. The Strano laboratory at MIT has a strong track record of working and publishing with undergraduate students and minorities; this grant will continue these efforts by supporting a female postdoc.