Periodic Reporting for period 1 - CircaSCOPE (Pre-commercialization of circadian clock-drug interactions screening tool for therapeutic applications)
Berichtszeitraum: 2022-04-01 bis 2023-09-30
Circadian disruption and misalignment are prevalent in the industrial world, due to our modern lifestyle, which include considerable exposure to light at night, sleep deprivation, shift-working and international flights. The impact of circadian disruption can be vast. For example, shift-workers are more susceptible to various pathologies, including cancer and type-2 diabetes. The health burden resulting from such circadian effects should be minimized. This can be partially done through optimization of therapies by considering their effects on the clock, and by targeting the clock for specific outcomes. It is therefore of paramount importance to identify and characterize the circadian effect of drugs for treatment optimization. This applies to both drugs already used as therapy and drugs that are under development.
We have recently developed CircaSCOPE (Circadian Single-Cell Oscillators PTC Extraction), a novel high-throughput method for PTC (Phase Transition Curves) reconstruction, which is based on live single-cell imaging and analysis to study clock resetting. In this project we have used CircaSCOPE to screen drug library for clock resetting, as a showcase the system’s capacity as well as relevance to the industry. We also made the first steps towards expanding CircaSCOPE methodology to various human cell types. Finally, we moved forward towards commercialization of the methodology.
We have recently developed CircaSCOPE (Circadian Single-Cell Oscillators PTC Extraction), a novel high-throughput method for PTC (Phase Transition Curves) reconstruction, which is based on live single-cell imaging and analysis to study clock resetting. In this project we have used CircaSCOPE to screen drug library for clock resetting, as a showcase the system’s capacity as well as relevance to the industry. We also made the first steps towards expanding CircaSCOPE methodology to various human cell types. Finally, we moved forward towards commercialization of the methodology.
We managed to successfully accomplish the scientific deliverable stated in our original research proposal namely, (i) Use CircaSCOPE to screen a comprehensive drug library, to showcase the system’s capacity as well as relevance to the industry - we identified several known and novel unknown resetting pathways by screening several different compound libraries. (ii) Make CircaSCOPE transferrable to various human cell types. We manage to generate lentiviral vector to deliver our dual-reporter system to cell lines and primary cells from human origin. We have generated a human cell line expressing the dual-reporter that might be useful for future studies with CircaSCOPE.
Our ability to efficiently use CircaSCOPE to screen drug libraries to identify novel pathways and compounds that reset the clock as well the potential capacity to do so in the future in human cells, open the door for exciting discoveries in respect to clock resetting in human. These findings carry important implications on human health and are expected to provide new therapeutic modalities for various related pathologies in the future.