NeuroNex Technology Hub: Bioluminescence for Optimal Brain Control and Imaging

从萤火虫到水母等动物都会发光，这一过程被称为生物发光。在自然界中，生物发光被用于捕获猎物、吸引配偶和自卫。当小分子与酶结合释放光子时，就会产生这种独特的光。研究人员已经将这种独特的生物发光形式用于各种各样的用途，从通过跟踪闪光来测量细胞活动，到通过将生物发光信号转化为电流来控制细胞活动。这些工具对于回答科学问题非常有用，也可能被证明是有用的新疗法，例如刺激大脑的特定区域或调节心脏起搏器。这个NeuroNex技术中心通过创新新的生物发光技术来推进科学，并向其他人传授这方面的知识。新的创新包括开发更明亮的化学反应，能够在大脑中传输更远的信号，以及创造新的显微镜来收集生物发光活动。技术中心还通过研讨会、派往实验室的使者和一个综合性网站，帮助其他科学家了解如何在他们自己的研究中使用这些方法的原则和实用细节。这个项目的另一个重点是制定从小学到高中的普通教育课程，以及在更广泛的社区内的推广项目。这个NeuroNex技术中心使生物发光用于细胞成像和控制。有效使用生物发光的历史障碍包括光产生的时间尺度延长和充电时间长（早期钙成像尝试的严重限制），以及光产生不足。技术中心和其他最近的进展直接解决了这些问题，例如，通过发现新分子，开发新的策略来赋予钙对明亮和快速荧光素酶的敏感性，以及通过共振能量转移来放大亮度。所有这些创新不仅服务于成像，而且使生物发光成为光遗传分子的驱动因素，这是一种新的细胞控制策略，称为生物发光光遗传学（“BL-OG”）。虽然BL-OG已经被证明是一种有效的解决方案，可以在单个分子中进行化学遗传和光遗传控制，但这里实现的进步显著地阐述和改善了这种功能。中心在向其他执业科学家提供技术转让方面的作用是为寻求培训的个人量身定制的。这种实用知识传播的特殊性是通过在布朗大学围绕与会者的需求设计研讨会，以及派遣受过生物发光训练的技术人员和学生直接到实验室演示和解决实验问题来实现的。综合网站列出了现有的生物发光选项，在哪里可以获得它们，以及汇总参考书目。在所有活动中，Hub团队寻求用户社区的积极输入，以确保所传播的知识有助于推进实践科学家的确切目标。这个神经技术中心奖是大脑计划和国家科学基金会理解大脑活动的一部分。

Animals ranging from fireflies to jellyfish produce light, a process known as bioluminescence. In nature, bioluminescence is used for prey capture, mate attraction and self-defense. This unique form of light production occurs when a small molecule combines with an enzyme to release photons. Researchers have harnessed this distinctive form of living light production for a wide variety of uses, from measuring activity in cells by tracking light flashes, to controlling activity in cells by transforming bioluminescent signals into electrical current flow. These tools are powerful for answering scientific questions, and may also prove useful as novel treatments, for example in stimulating specific areas of the brain or regulating heart pacemakers. This NeuroNex Technology Hub advances science by innovating new bioluminescent technologies, and teaching others about it. New innovations include the development of brighter chemical reactions, able to transmit signals farther across the brain, and the creation of new microscopes to harvest bioluminescent activity. The Technology Hub also helps other scientists learn both the principles and the pragmatic details of how to use these methods in their own research, through workshops, emissaries sent to laboratories, and a comprehensive website. An additional key focus of this project is on developing curricula for general education, from the grade school to the high school level, and on outreach projects within the broader community. This NeuroNex Technology Hub enables bioluminescence use for cellular imaging and control. Historical impediments to effective bioluminescence use included the prolonged time scale of light production and long recharging time (severe limitations in early calcium imaging attempts), and insufficient light production. The Technology Hub and other recent advances directly address these concerns, for example through discovery of new molecules, development of novel strategies for conferring calcium sensitivity to bright and fast luciferases, and brightness amplification e.g., by resonant energy transfer. All these innovations not only serve imaging, but also enable bioluminescence as a driver for optogenetic molecules, a new cellular control strategy termed BioLuminescent OptoGenetics ('BL-OG'). While BL-OG has already proven effective as a solution that allows chemigenetic and optogenetic control in a single molecule, the advances implemented here significantly elaborate and improve this functionality. The Hub role in providing technology transfer to other practicing scientists is tailored to the individuals seeking training. This specificity in dissemination of pragmatic knowledge is achieved by designing workshops at Brown University around the needs of attendees, and through sending bioluminescence-trained technicians and students directly to laboratories to demonstrate and trouble-shoot experiments. The comprehensive website lists existing bioluminescent options, where they can be acquired, and aggregate bibliographic references. In all activities, the Hub team seeks active input from the user community to ensure that the knowledge being disseminated is of use to advancing the exact goals of practicing scientists. This NeuroTechnology Hub award is part of the BRAIN Initiative and NSF's Understanding the Brain activities.