Live-Cell Fluorescence Lifetime FRET Assays for HTS

DESCRIPTION provided by applicant We seek to develop and commercialize a powerful technology platform to increase dramatically the effectiveness of drug discovery using high throughput screening HTS based on fluorescence lifetime FLT readouts of FRET in live cells This breakthrough is enabled by a combination of two complementary and synergistic technologies fluorescent biosensor engineering University of Minnesota UMN and fluorescence instrumentation engineering Fluorescence Innovations FI In Phase I we achieved our aims producing the first truly high throughput and high precision applications of FLT in living cells applied to a specific biosensor SERCA We also surpassed our aims by developing new instrumentation for high throughput spectral recording carrying out a SERCA screen on a compund library and developing FRET biosensors based on several new targets In addition several pharmaceutical companies expressed interest in this technology platform so UMN and FI started a new drug discovery company Photonic Pharma for the ultimate commercialization of these combined technologies In Phase II we will further develop this technology platform and apply it to a diverse array of targets thus clearly demonstrating the high potential for commercialization In In Aim we will seek improvements in hardware and software that will enhance future commercialization potential including a new instrument that combines FLT and spectral recording increased digitizer speed higher density plates connectivity with robotics and software improvements In Aim in order to demonstrate that our technology platform is widely applicable we will expand our list of biosensors focusing on targets of high commercial potential for which world leading experts are in close proximity at UMN These disease targets include heart failure drug abuse and addiction inflammation and cancer and muscle dystonia Biosensors will be engineered and expressed in live cells and screened against standard test and validation libraries to optimize the screening assay We will then carry out several large scale compound screens using optimized HTS assays Hit compounds will be retested as a function of compound concentration dose response and then subjected to functional assays performed by the above world class experts at UMN Promising hits may become leads for future medicinal chemistry development but the primary goal is to validate the discovery platform We are confident that the research conducted under these aims will set us up nicely for the commercialization phase by validating our business plan to combine UMN expertise in biosensor engineering and cell culture with FI expertise in instrumentation led by Photonic Pharma an emerging early phase drug discovery start up company Thus our business plan is not to sell instruments but to leverage our unique combination of biosensor and instrumentation expertise to develop and apply a technology platform that accelerates the early phase of drug discovery PUBLIC HEALTH RELEVANCE Fluorescence Innovations Inc in collaboration with the University of Minnesota proposes to greatly improve the technology for drug discovery during the crucial early stages of the process This technology has great commercial potential because it will make the process of drug discovery much more effective and efficient and is applicable to a wide range of health issues including heart failure diabetes cancer and drug addiction