Dr Owen Davies

Wellcome Senior Research Fellow

Contact details

Address

Street

Wellcome Centre for Cell Biology
Institute of Cell Biology
University of Edinburgh
Michael Swann Building
Max Born Crescent
Edinburgh

City
Post code
EH9 3BF

Background

2021-2026  Wellcome Senior Research Fellow

Institute of Cell Biology, University of Edinburgh

 

2014-2020  Wellcome Trust and Royal Society Sir Henry Dale Fellow

Institute for Cell and Molecular Biosciences, Newcastle University

 

2010-2013  Post-Doctoral Research Associate

Department of Biochemistry, University of Cambridge

 

2007-2009  Royal Commission for the Exhibition of 1851 Research Fellow

Institute for Stem Cell Research, University of Edinburgh

Qualifications

2007  PhD in Biochemistry

Department of Biochemistry, University of Cambridge

 

2003  BSc (Hons.) First Class in Medical Science

University of St. Andrews

Research summary

Structural biology of meiosis

Meiotic cell division is defined by a unique and highly dynamic programme of events that results in homologous chromosome segregation following crossover formation. In mammals, the telomeric ends of chromosomes become tethered to the nuclear envelope by the meiotic telomere complex, where they undergo rapid movements, driven by microtubule forces transmitted by the LINC complex, that facilitate the identification and alignment of homologous chromosome pairs through recombination. Once established, homologue chromosome pairs become synapsed along their length by the zipper-like assembly of the synaptonemal complex, which provides the unique three-dimensional architecture necessary for recombination intermediate resolution and crossover formation. Our research aims to uncover the structure, assembly mechanism and recombination function of the synaptonemal complex, the mechanistic basis of nuclear envelope tethering by the meiotic telomere complex and the mechanism of force transduction by the LINC complex. To achieve this, we adopt a structural biology approach of biophysics, crystallography and cryo-EM, coupled with collaborative structure-directed mutation in mouse meiosis. Ultimately, we aim to uncover how the mammalian synaptonemal complex, meiotic telomere complex and LINC complex operate together as an integrated molecular machine to achieve their essential functions of mammalian meiosis, and crucially how their dysfunction leads to human infertility, miscarriage and aneuploidy.

 

Postdoc positions available

I will be recruiting two postdoc positions to start in 2022 - please contact owen.davies@ed.ac.uk for details.

2021

Sandhu, S., Sou, E.I.F., Hunter, J.E., Salmon, L., Wilson, C.L., Perkins, N.D., Hunter, N., Davies, O.R., McClurg, U.L. (2021) Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12. Communications Biology, 4, 1371. https://doi.org/10.1038/s42003-021-02887-4

 

Dunce, 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

 

Thomas, C., Wetherall, B., Levasseur, M.D., Harris, R.J., Kerridge, S.T., Higgins, J.M.G., Davies, O.R. & Madgwick, S. (2021) A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes. Nature Communications, 12, 4322. https://doi.org/10.1038/s41467-021-24554-2

 

Morton, C.R., Rzechorzek, N.J., Maman, J.D., Kuramochi, M., Sekiguchi, H., Rambo, R., Sasaki, Y.C., Davies, O.R. & Pellegrini, L. (2021) Structural basis for the coiled-coil architecture of human CtIP. Open Biology, 11 (6), 210060. https://doi.org/10.1098/rsob.210060

 

Bhagwat, N.R., Owens, S.N., Ito, M., Boinapalli, J.V., Poa, P., Ditzel, A., Kopparapu, S., Mahalawat, M., Davies, O.R., Collins, S.R., Johnson, J.R., Krogan, N.J. & Hunter, N. (2021) SUMO is a pervasive regulator of meiosis. eLife, 10, e57720. https://doi.org/10.7554/eLife.57720

 

Gurusaran, M. & Davies, O.R. (2021) A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies. eLife, 10, e60175. https://doi.org/10.7554/eLife.60175

 

2020

Sánchez-Sáez, F., Gómez-H, L., Dunne, O.M., Gallego-Páramo, C., Felipe-Medina, N., Sánchez-Martín, M., Llano, E., Pendas, A.M. & Davies, O.R. (2020) Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility. Science Advances, 6 (36), eabb1660. https://doi.org/10.1126/sciadv.abb1660

 

Sánchez Rodríguez, F., Simpkin, A.J., Davies, O.R., Keegan, R.M. & Rigden, D.J. (2020) Helical ensembles outperform ideal helices in molecular replacement. Acta Crystallographica, D76, 962-970. https://doi.org/10.1107/S205979832001133X

 

Zhang, J., Gurusaran, M., Fujiwara, Y., Zhang, K., Echbarthi, M., Vorontsov, E., Guo, R., Pendlebury, D.F., Alam, I., Livera, G., Emmanuelle, M., Wang, P.J., Nandakumar, J., Davies, O.R. & Shibuya, H. (2020) The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells. Nature Communications, 11, 2055. https://doi.org/10.1038/s41467-020-15954-x

 

Thomas, J.M.H., Keegan, R.M., Rigden, D.J. & Davies, O.R. (2020) Extending the scope of coiled-coil crystal structure solution by AMPLE through improved ab initio modelling. Acta Crystallographica, D76, 272-284. https://doi.org/10.1107/S2059798320000443

 

Prior, C.B., Davies, O.R., Bruce, D. & Pohl, E. (2020) Obtaining tertiary protein structures by the ab-initio interpretation of small angle X-ray scattering data. J. Chemical Theory & Computation, 16, 3, 1985-2001. https://doi.org/10.1021/acs.jctc.9b01010

 

2019

Lepore, R., Kryshtafovych, A. . . . Davies, O.R. . . . Walton, J.D. & Schwede, T. (2019) Target highlights in CASP13: experimental target structures through the eyes of their authors. Proteins, 87 (12), 1037-1057. https://doi.org/10.1002/prot.25805

 

Voelkel-Meiman, K., Cheng, S.-Y., Parziale, M., Morehouse, S.J., Feil, A., Davies, O.R., de Muyt, A, Borde, V. & MacQueen, A.J. (2019) Crossover recombination and synapsis are linked by adjacent regions within the N terminus of the Zip1 synaptonemal complex protein. PLoS Genetics, 15 (6), e1008201. https://doi.org/10.1371/journal.pgen.1008201

 

Dunne, O.M. & Davies, O.R. (2019) A molecular model for self-assembly of the synaptonemal complex protein SYCE3. Journal of Biological Chemistry, 294 (23), 9260-9275. https://doi.org/10.1074/jbc.RA119.008404

 

Dunne, O.M. & Davies, O.R. (2019) Molecular structure of human synaptonemal complex protein SYCE1. Chromosoma, 28 (3), 223-226. https://doi.org/10.1007/s00412-018-00688-z

 

Levasseur, M.D., Thomas, C., Davies, O.R., Higgins, J.M.G. & Madgwick, S. (2019) Degron-masking controls cyclin B1:CDK1 activity to prevent cell division errors in oocytes. Developmental Cell, 48, 1-18. https://doi.org/10.1016/j.devcel.2019.01.008

 

2018

Dunce, J.M., Milburn, A.E., Gurusaran, M., da Cruz, I., Sen, L.T., Benavente, R. & Davies, O.R. (2018) Structural basis of meiotic telomere attachment to the nuclear envelope by MAJIN-TERB2-TERB1. Nature Communications, 9, 5355. https://doi.org/10.1038/s41467-018-07794-7

 

Dunce, J.M., Dunne, O.M., Ratcliff, M., Millan, C., Madgwick, S., Usόn, I. & Davies, O.R. (2018) Structural basis of meiotic chromosome synapsis through SYCP1 self-assembly. Nature Structural & Molecular Biology, 25, 557-569. https://doi.org/10.1038/s41594-018-0078-9

 

Yang, Y., Denton, H., Davies, O.R., Smith-Jackson, K., Kerr, H., Herbert, A.P., Barlow, P.N., Pickering, M.C. & Marchbank, K.J. (2018) An Engineered Complement Factor H Construct for Treatment of C3 Glomerulopathy. Journal of the American Society of Nephrology, 29 (6), 1649-1661. https://doi.org/10.1681/ASN.2017091006

 

2017

Syrjanen, J.S., Heller, I., Candelli, A., Davies, O.R., Peterman, E.J., Wuite, G., Pellegrini, L. (2017) Single-molecule observation of DNA compaction by meiotic protein SYCP3. eLife, 6, e22582. https://doi.org/10.7554/eLife.22582

 

2016

Gómez-H, L., Felipe-Medina, N., Sánchez-Martín, M., Davies, O.R., Ramos, I., Garcia-Tuñón, I., de Rooij, D., Barbero, J.L., Dereli, I., Tóth, A., Benavente, R., Llano, E., and Pendas, A. (2016) The anonymous C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex essential for mouse fertility. Nature Communications, 7, 13298. https://doi.org/10.1038/ncomms13298

 

Carroll,B., Maetzel, D., Maddocks, O.D., Otten, G., Ratcliff, M., Smith, G.R., Dunlop, E.A., Passos, J.F., Davies, O.R., Jaenisch, R., Tee, A.R., Sarkar, S., Korolchuk, V.I. (2016) Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity. eLife, 5, e11058. https://doi.org/10.7554/eLife.11058

 

2015

Davies, O.R., Forment, J.V., Sun, M., Belotserkovskaya, R., Coates, J., Galanty, Y., Demir, M., Morton, C., Rzechorzek, N., Jackson, S.P. & Pellegrini, L. (2015) CtIP tetramer assembly is required for DNA-end resection and repair. Nature Structural & Molecular Biology, 22, 150-157. https://doi.org/10.1038/nsmb.2937

 

2014

Syrjanen, J.S., Pellegrini, L. & Davies, O.R. (2014) A molecular model for the role of SYCP3 in meiotic chromosome organisation. eLife, 3, e02963. https://doi.org/10.7554/eLife.02963

 

2013

Davies, O.R., Lin, C.-Y., Radzisheuskaya, A., Zhou, X., Taube, J., Blin, G., Waterhouse, A., Smith, A.J.H. & Lowell, S. (2013) Tcf15 primes pluripotent cells for differentiation. Cell Reports, 3, 472-484. https://doi.org/10.1016/j.celrep.2013.01.017

 

2012

Davies, O.R., Maman, J.D. & Pellegrini, L. (2012) Structural analysis of the SYCE2-TEX12 complex provides molecular insights into synaptonemal complex assembly. Open Biology, 2, 120099. https://doi.org/10.1098/rsob.120099

 

2010

D’Arcy, S., Davies, O.R., Blundell, T.L. & Bolanos-Garcia, V.M. (2010) Defining the molecular basis of BubR1 kinetochore recruitment and APC/C-Cdc20 inhibition. Journal of Biological Chemistry, 285, 19, 14764-76. https://doi.org/10.1074/jbc.M109.082016

 

2008

Li, Y., Chirgadze, D.Y., Bolanos-Garcia, V.M., Sibanda, B.L., Davies, O.R., Ahnesorg, P., Jackson, S.P. & Blundell, T.L. (2008) Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ. EMBO Journal, 27, 1, 290-300. https://doi.org/10.1038/sj.emboj.7601942

 

2007

Davies, O.R. & Pellegrini, L. (2007) Interaction with the BRCA2 C terminus protects RAD51-DNA filaments from disassembly by BRC repeats. Nature Structural & Molecular Biology, 14, 6, 475-483. https://doi.org/10.1038/nsmb1251

 

2006

Shivji, M.K.K.*, Davies, O.R.*, Savill, J.M., Bates, D.L., Pellegrini, L. & Venkitaraman, A.R. (2006) A region of human BRCA2 containing multiple BRC repeats promotes RAD51-mediated strand exchange. Nucleic Acids Research, 34, 14, 4000-4011. https://doi.org/10.1093/nar/gkl505                                                                                

 

Bolanos-Garcia, V.M. & Davies, O.R. (2006) Structural analysis and classification of native proteins from E. coli commonly co-purified by immobilised metal affinity chromatography. Biochimica et Biophysica Acta (Gen), 1760, 9, 1304-1313. Review Article. https://doi.org/10.1016/j.bbagen.2006.03.027

 

Doré, A.S., Furnham, N., Davies, O.R., Sibanda, B.L., Chirgadze, D.Y., Jackson, S.P., Pellegrini, L. & Blundell, T.L. (2006) The Xrcc4-DNA ligase IV yeast ortholog complex reveals a novel BRCT interaction mode. DNA Repair, 5, 3, 362-368. https://doi.org/10.1016/j.dnarep.2005.11.004

 

Blundell, T.L., Sibanda, B.L., Montalvao, R.W., Brewerton, S., Chelliah, V., Worth, C.L., Harmer, N.J., Davies, O.R. & Burke, D. (2006) Structural biology and bioinformatics in drug design: opportunities and challenges for target identification and lead discovery. Philos Trans R Soc Lond B Biol Sci, 361, 1467, 413-23. Review Article. https://doi.org/10.1098/rstb.2005.1800