Our research approach is primarily directed towards structural studies of SC by reconstituting SC subcomplexes and assemblies from its largely coiled-coil protein components (SYCP1-3, SYCE1-3, TEX12 and SIX6OS1). This involves reconstitution of SC structures from recombinant proteins in vitro , and in heterologous mammalian cellular systems, with structure determination at atomic resolution by X-ray crystallography and cryo-electron microscopy, in solution by light and X-ray scattering, and across large scales by super-resolution fluorescence microscopy and cryo-electron tomography. Hence, our strategy is succinctly summarised by Richard Feynman:“ what I cannot create, I do not understand”. Through this bottom-up approach, we have discovered th e mammalian SC’s key building-block complexes, their structures and how they self-assemble into fibrous and paracrystalline structures that form the SC’s distinct architectural units. In parallel with this bottom-up approach, we are establishing a complementary top-down cellular structural biology strategy in which we aim to determine the molecular structure of the native SC within its biological environment and visualise recombination and crossover formation within its architectural framework. Our structural biology findings lead to critical insights into SC function in vivo through analysis of structure-based separation-of-function mutants in meiosis by mouse genetics collaborators. Further, we are analysing clinical mutations to determine how they affect SC structure/function and lead to human disease. Ultimately, we aim to achieve a complete molecular understanding of the structure and assembly mechanism of the SC, how it regulates recombination and crossover formation, and how its defects lead to human infertility, miscarriage and aneuploidy.