People  

Owen Davies

  • See a full publication list here.

 

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

Davies, Forment, Sun, Belotserkovskaya, Coates, Galanty, Demir, Morton, Rzechorzek, Jackson, 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

Davies, Maman & Pellegrini 2012 Structural Analysis of the Human SYCE2-TEX12 Complex Provides Molecular Insights into Synaptonemal Complex Assembly; Open Biology 2, 120099

 
Current Lab Members

James Dunce (Research Assistant and PhD student)

Gurusaran Manickam (PhD student)

Amy Milburn (PhD student)

 

Lab Alumni

Vincentius Aji Jatikusumo (Undergraduate student - 2015)

Omar Al-Jourani (MRes student)

Rowanne Allon (MSci student)

Katie Boothby (MSci student)

Olivia Dool (Undergraduate student)

Orla Dunne (Research Associate) 

Carmen Espejo Serrano (Erasmus student)

Jack Hughes (MSci student)

Scott Johnson (Undergraduate)

Kaiqing (Clark) Li (Undergraduate)

Matthew Ratcliff (Research Assistant)

Chandni Ravindan (Research Assistant)

Tom Rickards (Undergraduate student)

Lucy Salmon (PhD student) 

Natalija Stepurko (Undergraduate Research Assistant)