I/UCRC: Characterization and Bioengineering of Optogenetic Rhodopsins

项目主任推荐生物光子传感器和系统中心 (CBSS) 提案#1230851 Thomas Bifano 该提案为位于波士顿大学的生物光子传感器和系统中心寻求资金。基础研究的资助申请由 NSF 批准的征集 NSF 11-570 授权。此次征集邀请 I/UCRC 提交支持行业定义的基础研究的提案。膜生物物理学、神经生理学和分子生物学的最新发展为“光遗传学”这一新领域的诞生提供了催化剂。光遗传学依赖于神经元膜中几种不寻常的微生物视紫红质的表达，包括用于光激活神经的通道视紫红质（ChR）和用于光沉默神经的古视紫红质（AR3）。需要了解这些蛋白质的分子机制，然后进行自下而上的生物工程来规避当前的限制。该项目将重点应用波士顿大学 (BU) 和加州大学戴维斯分校开发的一套强大的光谱和生物分子工程技术。该项目涉及多个行业合作伙伴以及来自波士顿大学、加州大学戴维斯分校、麻省理工学院、哈佛大学和德克萨斯大学的光遗传学和视紫红质领先专家团队的密切合作。拟议项目的影响包括研究大脑功能、治疗大脑疾病和恢复视网膜退行性疾病视力的潜在变革方法。该项目的可交付成果是：(1) ChR 和 AR3 的改进版本，具有红移可见光吸光度、改进的动力学和改进的电压响应，以及 (2) 记录光遗传学研究工具和产品愿景的产品要求。 I/UCRC 的行业支持以及对该研究项目的积极参与，为有才华的工程师和科学家进入行业提供了渠道，从而增强了研究生教育体验。通过提供工业职业选择、非正式指导和与 I/UCRC 合作伙伴的实习，BU 将进一步加强对开发 STEM 领域代表性不足群体的学术潜力的承诺。

Program Director's Recommendation Center for Biophotonic Sensors and Systems (CBSS) Proposal # 1230851 Thomas Bifano This proposal seeks funding for the Center forBiophotonic Sensors and Systems located at Boston University. Funding Requests for Fundamental Research are authorized by an NSF approved solicitation, NSF 11-570. The solicitation invites I/UCRCs to submit proposals for support of industry-defined fundamental research. Recent developments in membrane biophysics, neurophysiology and molecular biology have provided the catalyst for the birth of a new field termed "optogenetics". Optogenetics relies on the expression of several unusual microbial rhodopsins in the neuronal membrane including channelrhodopsin (ChR) for light activating nerves and Archaerhodopsin (AR3) for light silencing nerves. There is a need to understand the molecular mechanisms of these proteins followed by bottoms-up bioengineering to circumvent current limitations. This project will focus on application of a set of powerful spectroscopic and biomolecular engineering techniques developed at Boston University (BU) and UC Davis. The project involves close collaboration with several industry partners and a team of leading experts in optogenetics and rhodopsins from BU, UC Davis, MIT, Harvard and the University of Texas. Impact of the proposed project includes potentially transformative approaches to study brain function, treatment for brain disorders and restoring vision for retinal degenerative diseases. The deliverables from this project are: (1) Improved versions of ChR and AR3 with red-shifted visible absorbance, improved dynamics and improved voltage response, and (2) Document product requirements for optogenetic research tools and product vision. The industry support of the I/UCRC and active participation in this research program enhances the graduate educational experience by providing a pipeline for talented engineers and scientist to industry. BU's commitment to develop the academic potential of underrepresented groups in STEM fields will be further enhanced by offering industrial career options, informal mentorships and internships with the I/UCRC partners.