NeuroNex Technology Hub: Bioluminescence for Optimal Brain Control and Imaging

NeuroNex 技术中心：用于最佳大脑控制和成像的生物发光

• 批准号: 1707352
• 负责人: Christopher Moore
• 金额: $ 362万
• 依托单位: Brown University
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1707352&HistoricalAwards=false
• 关键词: NeuroNex; Technology; Hub; Bioluminescence; Optimal

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.

从萤火虫到水母的各种动物都会发光，这一过程被称为生物发光。在自然界中，生物发光被用来捕捉猎物、吸引配偶和自卫。当小分子与酶结合释放光子时，这种独特的光产生形式就会发生。研究人员已经利用这种独特的生命光产生方式进行了广泛的用途，从通过跟踪闪光来测量细胞的活动，到通过将生物发光信号转换为电流来控制细胞的活动。这些工具在回答科学问题方面非常强大，也可能被证明是有用的新疗法，例如在刺激大脑的特定区域或调节心脏起搏器方面。这家NeuroNex技术中心通过创新新的生物发光技术来推动科学发展，并向其他人传授这一技术。新的创新包括开发更明亮的化学反应，能够将信号传递到大脑更远的地方，以及创造新的显微镜来获取生物发光活动。技术中心还通过研讨会、派往实验室的使者和一个全面的网站，帮助其他科学家了解如何在自己的研究中使用这些方法的原则和实用细节。该项目的另一个主要重点是制定从小学到高中的普通教育课程，并在更广泛的社区内开展外联项目。这款NeuroNex技术中心可将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(早期钙成像尝试受到严重限制)，以及光产生不足。技术中心和其他最新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的荧光素酶的敏感性，以及亮度放大，例如通过共振能量转移。所有这些创新不仅服务于成像，还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，允许在单个分子中进行化学遗传和光遗传控制，但这里实现的进展显著地细化和改进了这一功能。向其他执业科学家提供技术转让的中心角色是为寻求培训的个人量身定做的。这种传播语用知识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，并通过直接派遣经过生物发光培训的技术人员和学生到实验室演示和故障排除实验来实现的。这个综合的网站列出了现有的生物发光选择，在哪里可以获得它们，并汇总了参考文献。在所有活动中，Hub团队从用户社区寻求积极的投入，以确保传播的知识对推动执业科学家的确切目标有用。这个神经技术中心奖是大脑倡议和NSF了解大脑活动的一部分。

项目成果

Miniaturized Devices for Bioluminescence Imaging in Freely Behaving Animals

用于自由行为动物生物发光成像的微型设备

• DOI: 10.1109/embc44109.2020.9175375
• 发表时间: 2020
• 期刊: 2020 42nd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC
• 作者: Celinskis, Dmitrijs;Friedman, Nina;Koksharov, Mikhail;Murphy, Jeremy;Gomez-Ramirez, Manuel;Borton, David;Shaner, Nathan;Hochgeschwender, Ute;Lipscombe, Diane;Moore, Christopher
• 通讯作者: Moore, Christopher

Aequorea's secrets revealed: New fluorescent proteins with unique properties for bioimaging and biosensing.

• DOI: 10.1371/journal.pbio.3000936
• 发表时间: 2020-11
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Lambert GG;Depernet H;Gotthard G;Schultz DT;Navizet I;Lambert T;Adams SR;Torreblanca-Zanca A;Chu M;Bindels DS;Levesque V;Nero Moffatt J;Salih A;Royant A;Shaner NC
• 通讯作者: Shaner NC

Developing biolight-based molecular technologies for simultaneous mapping, imaging, and controlling neural activity

开发基于生物光的分子技术，用于同步绘图、成像和控制神经活动

• DOI: 10.1364/brain.2021.btu3b.2
• 发表时间: 2021
• 期刊: BRAIN 2021 - Part of Biophotonics Congress: Optics in the Life Sciences 2021
• 作者: Crespo, Emmanuel Luis;Pal, Akash;Prakash, Mansi;Gomez-Ramirez, Manuel;Zaidi, Zohair;Coon, Nicholas;Medendorp, William;Dash, Suneeti;Brown, Tariq;Shaner, Nathan
• 通讯作者: Shaner, Nathan