Craniosynostosis is a birth defect with a prevalence of 1 in 2,500 births. Premature closure of cranial sutures has profound effects on brain development as well as the size and shape of the future head and face. Craniosynostosis is often progressive and presents on-going clinical problems in the life of the affected child and adolescent until skeletal maturity. This often leads to a heavy ‘burden of care’ with repeated surgical interventions. Previous research has shown that cyclical mechanical loading of cranial bone in rat and rabbit models has been able to significantly delay the normal fusion of cranial sutures during postnatal development. Preliminary data from our own research has shown that mechanical loading of calvarial bone can delay or prevent the onset of craniosynostosis in a mouse model for Crouzon syndrome. In this proposal we would like to further optimise the loading procedure to determine the precise conditions under which calvarial loading has the biggest impact on postnatal progressive craniosynostosis. At the same time, we aim to investigate the cellular and molecular events downstream of calvarial bone mechanotransduction to further understand the underlying mechanism. If successful this proposal has the potential to be the first important step towards the development of a non-invasive, non-surgical treatment alternative for children born with progressive craniosynostosis.