Project description
Unlocking the mechanisms behind limb development
Many people suffer from conditions or congenital defects affecting joint and limb function, severely affecting their daily lives. It is therefore deemed important to uncover the underlying mechanisms behind joint function and limb formation. The EU-funded COMPLIMB project seeks to create a groundbreaking computational model to predict vertebrate limb development. It will closely study how specific changes affect joint development and limb growth. These observations will then be integrated into a powerful computational model. This model could serve as an important predictive tool to better treat joint deformities and improve detection of congenital defects in humans.
Objective
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.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF-GF - Global FellowshipsCoordinator
08034 Barcelona
Spain