Optical Tools for Analyzing and Repairing Biological Systems
用于分析和修复生物系统的光学工具
Ed Boyden
ABSRACT
Understanding and repairing complex biological systems, such as the brain, requires technologies for systematically observing and controlling these systems. We are discovering new molecular principles that enable such technologies. For example, we discovered that one can physically magnify biological specimens by synthesizing dense networks of swellable polymer throughout them, and then chemically processing the specimens to isotropically swell them. This method, which we call expansion microscopy, enables ordinary microscopes to do nanoimaging – important for mapping the brain across scales. As a second example, we discovered that microbial opsins, genetically expressed in neurons, could enable their electrical activities to be precisely controlled in response to light. These molecules, now called optogenetic tools, enable causal assessment of how neurons contribute to behaviors and pathological states, and are yielding insights into new treatment strategies for brain diseases. Finally, we are developing, using new strategies such as robotic directed evolution, fluorescent reporters that enable the precision measurement of signals such as voltage and calcium. By fusing such reporters to self-assembling peptides, they can be stably clustered within cells at random points, distant enough to be resolved by a microscope, but close enough to spatially sample the relevant biology. Such clusters, which we call signaling reporter islands (SiRIs), permit many fluorescent reporters to be used within a single cell, to simultaneously reveal relationships between different signals.
近年来，我们不断探寻新的分子原理与技术，并用于理解和修复复杂的生物系统（如大脑）。例如，通过合成致密的可膨胀聚合物网络来放大生物样本并配合化学处理，使其能够各向同性膨胀。这种方法被成为扩展显微镜，能够使普通显微镜进行纳米成像，对于在不同尺度下描绘大脑至关重要。此外我们发现，神经元中基因表达的微生物视蛋白使其电活动能够在光的反应下被精确控制，这类分子被称为光遗传学工具，能够对神经元如何影响行为和病理状态进行因果评估，并为脑疾病的新治疗策略带来新的见解。最后，我们使用机器人定向进化等新策略开发荧光报告器，用于精确测量电压和钙等信号。将其融合到自组装肽上，它们能够在细胞内稳定地聚集在一起，当距离足够远时，可以用显微镜分辨，而当距离足够近时，能够在空间上对相关生物进行取样。这种称为信号报告岛的簇群，能够在单个细胞内使用多个荧光报告器，以同时揭示不同信号之间的关系。
BIOGRAPHY
Ed Boyden is Y. Eva Tan Professor in Neurotechnology at MIT, an investigator of the Howard Hughes Medical Institute and the MIT McGovern Institute, and professor of Brain and Cognitive Sciences, Media Arts and Sciences, and Biological Engineering at MIT. He leads the Synthetic Neurobiology Group, which develops tools for analyzing and repairing complex biological systems such as the brain, and applies them systematically to reveal ground truth principles of biological function as well as to repair these systems. Ed received his Ph.D. in neurosciences from Stanford University as a Hertz Fellow, working in the labs of Jennifer Raymond and Richard Tsien, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. In parallel to his PhD, as an independent side project, he co-invented optogenetic control of neurons, which is now used throughout neuroscience. He went on to earn three degrees in electrical engineering and computer science, and physics, from MIT, graduating at age 19, while working on quantum computing in Neil Gershenfeld's group. He co-directs the MIT Center for Neurobiological Engineering, which aims to develop new tools to accelerate neuroscience progress, and is a faculty member of the MIT Center for Environmental Health Sciences, Computational & Systems Biology Initiative, and Koch Institute.
Amongst other recognitions, he has received the Wilhelm Exner Medal (2020), the Croonian Medal (2019), the Lennart Nilsson Award (2019), the Warren Alpert Foundation Prize (2019), the Rumford Prize (2019), the Canada Gairdner International Award (2018), the BBVA Foundation Frontiers of Knowledge Award (2015), the Carnegie Prize in Mind and Brain Sciences (2015), the Jacob Heskel Gabbay Award (2013), the Grete Lundbeck Brain Prize (2013), the NIH Director's Pioneer Award (2013). He was also named to the World Economic Forum Young Scientist list (2013) and the Technology Review World’s "Top 35 Innovators under Age 35" list (2006), and is an elected member of the National Academy of Sciences (2019), the American Academy of Arts and Sciences (2017), the National Academy of Inventors (2017), and the American Institute for Medical and Biological Engineering (2018).
Ed Boyden教授现为麻省理工学院Y. Eva Tan神经技术领域教授，Howard Hughes医学院和麻省理工学院McGovern研究所的研究员。他领导合成神经生物学小组，重点研发分析和修复大脑等复杂生物系统的工具，并用于揭示生物功能的基本原理并修复这些系统。他19岁从麻省理工学院同时获得电气工程、计算科学以及物理学位，之后从斯坦福大学获得神经科学博士学位，博士期间，还共同研发了神经元的光遗传学控制，并已经在整个神经科学中得到了应用。同时，他担任麻省理工学院神经生物学工程中心的联合主任，旨在开发新的工具来加速神经科学的进步。
Ed Boyden教授获得了诸多奖项的认可，包括Wilhelm Exner奖牌（2020年）、Croonian奖牌（2019年）、BBVA基金会知识前沿奖（2015年）、卡内基心理与脑科学奖（2015年）、美国国立卫生研究院院长先锋奖（2013年）。同时，他先后入选美国国家科学院（2019年）、美国艺术和科学院（2017年）、美国国家发明家学会（2017年）的成员。关于Ed Boyden研究小组的更多介绍，请参考课题组主页：http://synthneuro.org/。