Objective The circadian clock is the biological mechanism that directs the physiological ~24 hour oscillations that most living organisms undergo to anticipate the daily pattern of light. In mammals, that rhythmicity results from a highly conserved genetic circuit –based on transcriptional and post-transcriptional regulation– that works synchronously at a cellular level and differs among tissues. Around the 10% of the mammalian proteins, including essential components of the cell cycle and differentiation pathways have been categorised as circadian. Thus, a clock dysregulation may have pathological consequences, which is the case in some types of cancer. Although synchronous circadian cells share a common mechanical microenvironment, the contribution of mechanics to the clock maintenance has never been addressed. To fill this gap, the aim of this project is to unravel a) the impact of the mechanical microenvironment on the cellular clock, b) the influence of circadian oscillations on the mechanical behaviour of the cells and c), the interplay between mechanics and the clock during stem cell differentiation. To achieve these goals, we will combine state-of-the-art technologies in cell mechanics, molecular biology, imaging, and computational modelling. As model system we will use entrained MCF-10a and PHK stem cells. By subjecting them to a range of extracellular matrix rigidities, we will measure the influence of mechanics on the circadian expression of core clock, cytoskeleton and differentiation genes. We will then use traction force microscopy to study the rhythmicity of cell mechanics and, through computational tools, we will link gene expression patterns and force oscillatory behaviour in order to elucidate the molecular basis of the ‘biomechanical clock’.This interdisciplinary study will add a new layer of regulation to both cell mechanics and the circadian clock. As such, the results obtained here will potentially impact on the field of chronomedicine. Fields of science natural sciencesphysical sciencesopticsmicroscopymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologynatural sciencesbiological scienceszoologymammalogynatural sciencesbiological sciencesmolecular biology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2016 - Individual Fellowships Call for proposal H2020-MSCA-IF-2016 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA Net EU contribution € 158 121,60 Address CARRER BALDIRI REIXAC PLANTA 2A 10-12 08028 Barcelona Spain See on map Region Este Cataluña Barcelona Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 158 121,60