Investigating the spinal biomechanics of zebrafish: Insights into vertebral structure and function with implications for human skeletal bone health (360G-Wellcome-334448_Z_25_Z)

Back pain is the leading cause of disability in the UK, with lower back pain accounting for over 11% of the total national burden. Yet, the biomechanical basis of spinal ageing and degeneration remains poorly understood. This project investigates the mechanical performance of the ageing vertebral column using zebrafish, a genetically tractable and imaging-accessible vertebrate model that mimics many key features of human skeletal biology, including axial loading and vertebral deterioration with age. We will apply finite element analysis, microCT, synchrotron imaging, and morphometrics to quantify how vertebral mechanics change across the life course and between sexes. These analyses will test how stress, strain, and vertebral deformation vary with age, and identify regions of potential mechanical failure relevant to human conditions such as osteoporosis and spinal stenosis. Crucially, we will incorporate a zebrafish mutant that undergoes premature vertebral skeletal ageing (lmx1b) to model early-onset spinal decline, a feature with strong translational relevance. In parallel, we will use confocal imaging and histological staining to examine cellular and matrix-level changes in vertebral tissues, linking structural mechanics to underlying biological processes. This multi-scale approach will examine vertebral ageing, sex differences in spinal robustness, and the biomechanical foundations of back pain and spinal disease.