Institute for Cell and Molecular Biosciences

Staff Profile

Dr Owen Davies

Wellcome Trust and Royal Society Sir Henry Dale Fellow

Research

The molecular basis of mammalian meiosis

The structure and function of the human synaptonemal complex

Our research aims to uncover the molecular basis of mammalian meiosis, with a particular focus on meiotic chromosome structure and the mechanistic basis of meiotic recombination and crossover formation. In the first meiotic division, homologous chromosome pairs are held together in synapsis by a 'zipper'-like protein assembly, the synaptonemal complex (SC). The three-dimensional architecture of the SC imposes a unique structure upon meiotic chromosomes and also provides the physical framework for meiotic recombination and crossover formation. These processes are achieved through homologous recombination-mediated DNA double-strand break repair pathways, are entirely dependent on the correct assembly of the SC, and are essential for fertility and prevention of aneuploidy. We aim to elucidate the molecular structure of the human SC, its interaction with chromosomal DNA, and how it interacts with DNA repair factors to achieve recombination and crossover formation.

We adopt a biochemical and structural biology approach to tackling this challenging and fundamental problem of cellular function. Our primary research techniques are biochemistry, biophysics (including SEC-MALS and electron microscopy) and X-crystallography, which we use to study recombinantly produced components and multi-component assemblies of the human SC.

Ultimately, we aim to define the molecular structure and function of the synaptonemal complex in meiosis, the mechanisms that control its dynamic assembly and disassembly in meiotic cells, and how its defective formation leads to human infertility and recurrent miscarriage. This knowledge will be essential in developing new diagnostic tools for determining the molecular basis of infertility and miscarriage, and may further lead to the development of new assisted reproduction technologies directed towards conditions for which there are currently no treatment options.

Selected publications:


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.

Dunce, J.M., Milburn, A.E., Manickam, G., 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.

Davies OR, Forment JV, Sun M, Belotserkovskaya R, Coates J, Galanty Y, Demir M, Morton CR, Rzechorzek NJ, Jackson SP, Pellegrini L. (2015) CtIP tetramer assembly is required for DNA-end resection and repair. Nature Structural and Molecular Biology, 22, 150-157

Syrjanen, Pellegrini & Davies (2014) A Molecular Model for the Role of SYCP3 in Meiotic Chromosome Compaction; eLife 3, e02963


Current Lab Members:

James Dunce (Research Assistant and PhD student)

Orla Dunne (Postdoctoral Research Associate)

Gurusaran Manickam (PhD student)

Amy Milburn (PhD student)


Chandni Ravindan  (PhD student - joint with Amy MacQueen, Wesleyan University, Connecticut, USA)



Lab alumni

Vincentius Aji Jatikusumo (Undergraduate student - 2015)

Katie Boothby (MSci student - 2015-2016)

Matthew Ratcliff (MRes student and Research Assistant - 2015-2016)


Lucy Salmon (PhD student) 



Urszula McClurg (Faculty Research Fellow)



Lee Sen (MRes student)




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PhD Positions Available

PhD studentship in Biochemistry and Structural Biology – The molecular structure and function of the synaptonemal complex in chromosome synapsis and recombination during meiosis.

Application deadline 11th January 2019. For more details and to apply please follow this link.


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Publications