Pre-commercialization of circadian clock-drug interactions screening tool for therapeutic applications

Informations projet

CircaSCOPE

N° de convention de subvention: 101060296

DOI

10.3030/101060296

Projet clôturé

Date de signature de la CE 24 Mars 2022

Date de début 1 Avril 2022

Date de fin 30 Septembre 2023

Financé au titre de

• European Research Council (ERC)

Coût total

Aucune donnée

Contribution de l’UE

€ 150 000,00

Coordonné par

WEIZMANN INSTITUTE OF SCIENCE
Israel

Periodic Reporting for period 1 - CircaSCOPE (Pre-commercialization of circadian clock-drug interactions screening tool for therapeutic applications)

Période du rapport: 2022-04-01 au 2023-09-30

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

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.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

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.