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

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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.