Collaborative Research: EAGER: Customized cell biosensors for interrogating cancer cell physiology

了解正常和癌变肿瘤细胞的生理状态限制了我们对细胞如何生长和对环境作出反应的理解。在这个合作项目中，pi将构建可与其他细胞混合的合成活生物传感器，以提供关于细胞生理状态的易于检测和可测量的信息，包括肿瘤细胞对治疗药物的反应。这将提高我们模拟正常细胞和癌细胞生物学的能力，有助于我们了解潜在的治疗药物如何影响细胞。该信息将以一种高通量方式同时检测多种生理状态的方式提供。就更广泛的影响而言，该项目将通过每个机构的几个正在进行的项目以及加强机构之间互动的新活动，加强正在进行的外展活动，以吸引本科生、K-12学生和公众参与STEM。该项目将开发合成生物学工具和实验方法，以开发更复杂的正常和癌细胞生理特性模型，包括有关直接环境和对治疗剂反应的信息。第一步将是开发基因编码的活细胞传感器，该传感器将报告多种细胞生理状态的信息，包括治疗生物标志物。第二步将是通过装载条形码合成RNA分子来开发传感器的实时报告，这些合成RNA分子对于每个生物标志物都是不同的，以便在一个具有成本效益的高通量平台上进行检测。这个EAGER的目标是开发和验证成功所需的每一个关键技术基础。就更广泛的影响而言，该项目将有助于培养合成、细胞和癌症生物学方面的下一代劳动力。该项目还将包括跨机构的虚拟会议，以加强各机构iGEM团队的学生网络。

Understanding the physiological state of normal and cancerous tumor cells has limited our understanding of how cells grow and respond to their environment. In this collaborative project the PIs will construct synthetic living biosensors that can be mixed with other cells to provide readily detectable and measurable information on the cells physiological state, including the response of tumor cells to therapeutic agents. This will improve our ability to model normal and cancer cell biology, contributing to our understanding of how potential therapeutic agents affect cells. This information will be provided in a manner for detecting multiple physiological states simultaneously, in a high-throughput manner. In terms of broader impacts this project will enhance ongoing outreach activities to engage undergraduate students, K-12 students, and the public in STEM via several ongoing programs at each institution as well as by new activities to enhance interactions between institutions. This project will develop synthetic biology tools and experimental approaches that will enable the development of more sophisticated models of normal and cancer cell physiological properties, including information about the immediate environment and response to therapeutic agents. The first step will be to develop genetically encoded live cell sensors that will report information about multiple cell physiological states, including treatment biomarkers. The second step will be to develop real-time reporting by the sensors via loading of barcoded synthetic RNA molecules distinct for each biomarker to be detected in a cost-effective, high-throughput platform. The goal of this EAGER is to develop and validate each of the key technological foundations required to be successful. In terms of broader impacts, this project will contribute to the training of the next generation work-force in synthetic, cellular, and cancer biology. This project will also include cross-institutional virtual meetings to enhance student networking by the iGEM teams at each institution.