Descrizione del progetto
Sbloccare i meccanismi alla base dello sviluppo degli arti
Molte persone soffrono di condizioni o difetti congeniti che compromettono la funzionalità delle loro articolazioni e degli arti, compromettendo in modo grave la loro vita quotidiana. Si ritiene pertanto importante scoprire i meccanismi alla base della funzione articolare e della formazione degli arti. Il progetto COMPLIMB, finanziato dall’UE, cerca di creare un modello di calcolo rivoluzionario per prevedere lo sviluppo degli arti nei vertebrati. Studierà da vicino il modo in cui cambiamenti specifici influenzano lo sviluppo articolare e la crescita degli arti. Queste osservazioni saranno poi integrate in un potente modello computazionale. Un tale modello potrebbe servire come importante strumento predittivo per trattare meglio le deformità articolari e migliorare il rilevamento dei difetti congeniti negli esseri umani.
Obiettivo
Understanding the roles of motion and mechanotransduction in joint formation holds promise for the study and treatment of joint deformities in humans. Joint development has been widely studied in axolotls (Ambystoma mexicanum), as these animals regrow whole limbs throughout their life. Axolotl limbs are morphologically similar to human limbs and utilize the same biological rubrics as ontogenic growth. To draw from the therapeutic potential of these similarities, we propose to build a multi-scale multi-physics computational model for the prediction of vertebrate limb development. Our model will be based on in vivo data obtained using novel imaging techniques via NSF-funded experiments on axolotl limb growth, and will be utilised to determine the physical mechanisms of normal and pathological joint morphogenesis. To this end, in AIM 1 we will build a finite element model of growth at the tissue level to study how specific changes in limb motion regulate joint morphology. Next, in AIM 2 we will build a model of growth at the molecular level to determine how biochemical and biomechanical signalling pathways interact during normal and pathological joint development. Finally, in AIM 3 we will integrate both experimental and computational data from the different length scales into a single multi-scale mechano-biochemical model of vertebrate limb growth. A computational model that links the biomechanics and biochemistry of normal and pathological limb development at the subcellular, cellular and tissue scales is a powerful predictive tool. We envisage this tool will be utilised to optimise treatment therapies for joint deformities and better inform the preventive screening of congenital defects in humans.
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF-GF - Global FellowshipsCoordinatore
08034 Barcelona
Spagna