Structural biology of meiotic chromosome synapsis and recombination. Owen Davies is a Wellcome Senior Research Fellow and Professor of Structural Biology at the Centre for Cell Biology. After graduating from the University of St. Andrews with a BSc (Hons) in Medical Science in 2003, he studied for a PhD at the University of Cambridge with Prof. Sir Tom Blundell and Prof. Luca Pellegrini. Upon completion in 2007, he was awarded a Royal Commission for the Exhibition of 1851 Research Fellowship for postdoctoral study at the University of Edinburgh with Prof. Sally Lowell. He then returned to the University of Cambridge in 2010, where he established his career research interest in the meiotic synaptonemal complex in Prof. Luca Pellegrini’s laboratory. Owen Davies Owen was awarded a Wellcome Sir Henry Dale Fellowship in 2014 to establish his independent laboratory to study the synaptonemal complex at the University of Newcastle. In 2021, he moved to the Centre for Cell Biology at the University of Edinburgh as a Wellcome Senior Research Fellow (2021-2026) to study the structural basis of chromosome synapsis and recombination in meiosis. Davies Lab Website Lab members Eleanor Casey, Simona Debilio, Peter Donlon, Denzel Gonzales, Megan Hine, Hira Husain, Noor Fatima Khalid, Nitobe London, Gurusaran Manickam, Pracheta Pal, and Miguel Pachon Penalba Research How is the chromosome number halved during meiosis to create spermatozoa and oocytes? This involves a unique and elegant choreography in which chromosomes search throughout the cell to find their homologous partners, with which they recombine, synapsis and exchange genetic material by crossing over, before segregating upon cell division. At the centre of this process is the synaptonemal complex (SC), a zipper-like protein assembly that binds together homologous chromosomes during the critical stages of recombination. The SC consists of a midline central element and chromosome-bound lateral elements, is 100-nm wide and extends along the chromosome length (up to 25 micrometres). This supramolecular assembly directs the resolution of recombination events between chromosomes into crossovers that generate genetic diversity and are essential for fertility. However, the molecular structure and recombination function of the SC have remained unknown since its discovery almost 70 years ago. Our research aims to answer these longstanding questions of cell biology by determining the structure of the SC’s constituent proteins and complexes, how they interact into the full SC, and how the SC’s three-dimensional structure regulates recombination and crossover formation.Our main research questions are:What is the molecular structure of the synaptonemal complex?How is the SC dynamically assembled and disassembled within the cell?How does local SC structure direct meiotic recombination and crossover formation?How do dysfunctions in the SC lead to infertility, miscarriage and aneuploidy?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 the 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. Selected publications Gurusaran, M., Zhang, J., Zhang, K., Shibuya, H., Davies, O.R. (2024) MEILB2-BRME1 forms a V-shaped DNA clamp upon BRCA2-binding in meiotic recombination. Nature Communications, 15, 6552.https://doi.org/10.1038/s41467-024-50920-xCrichton, J.H., Dunce, J.M., Dunne, O.M., Salmon, L.J., Devenney, P.S., Lawson, J., Adams, I.R. & Davies, O.R. (2023) Structural maturation of SYCP1-mediated meiotic chromosome synapsis by SYCE3. Nature Structural and Molecular Biology, 30, 188-199.https://doi.org/10.1038/s41594-022-00909-1Dunce, J.M., Salmon, L.J. & Davies, O.R. (2021) Structural basis of meiotic chromosome synaptic elongation through hierarchical fibrous assembly of SYCE2-TEX12. Nature Structural and Molecular Biology, 28, 681-693. https://doi.org/10.1038/s41594-021-00636-z This article was published on 2026-04-23
