I/UCRC: Characterization and Bioengineering of Optogenetic Rhodopsins

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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.