Obiettivo 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. Campo scientifico natural sciencesphysical sciencesopticsmicroscopymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologynatural sciencesbiological scienceszoologymammalogynatural sciencesbiological sciencesmolecular biology Programma(i) 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 Argomento(i) MSCA-IF-2016 - Individual Fellowships Invito a presentare proposte H2020-MSCA-IF-2016 Vedi altri progetti per questo bando Meccanismo di finanziamento MSCA-IF-EF-ST - Standard EF Coordinatore FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA Contribution nette de l'UE € 158 121,60 Indirizzo CARRER BALDIRI REIXAC PLANTA 2A 10-12 08028 Barcelona Spagna Mostra sulla mappa Regione Este Cataluña Barcelona Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 158 121,60