Descripción del proyecto
Desvelar los mecanismos tras el desarrollo de las extremidades
Muchas personas padecen afecciones o defectos congénitos que afectan a la función de las articulaciones y extremidades, lo que repercute gravemente en su vida cotidiana. Por eso, se considera que es importante descubrir los mecanismos subyacentes a la función articular y a la formación de las extremidades. El proyecto COMPLIMB, financiado con fondos europeos, tiene por objeto crear un modelo computacional innovador para predecir el desarrollo de las extremidades de los vertebrados. Estudiará atentamente cómo afectan los cambios específicos al desarrollo de las articulaciones y al crecimiento de las extremidades. Después, estas observaciones se integrarán en un potente modelo computacional. Este modelo podría convertirse en una herramienta de predicción importante para tratar mejor las deformidades articulares y mejorar la detección de defectos congénitos en humanos.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-GF - Global FellowshipsCoordinador
08034 Barcelona
España