Principal Supervisor: Dr Eugenio Sanchez-Moran, School of Biosciences
Co-supervisor: Dr Lindsey Jane Leach, School of Biosciences; Professor Chris Franklin, School of Biosciences; Kim Osman
PhD project title: Programmed remodelling of the chromosome axis: understanding its impact on the distribution of genetic crossovers during meiosis.
University of Registration: University of Birmingham
The aim of this project is to understand how programmed remodelling of the chromosome axis that organizes chromosomes during meiosis influences the formation and distribution of genetic crossovers during meiosis. Acquiring this knowledge will make an important contribution to ensuring Food Security over forthcoming years, which remains one of the key challenges confronting society.
The development and introduction of new elite varieties of crops remains time consuming, often taking 10 years or more. A key reason is that crop breeding methods remain primarily reliant on meiotic recombination to generate genetic variation through the formation of genetic crossovers (COs) that produce new combinations of genes. Herein lies one of the major limitations confronted by plant breeders if they are to develop strategies for faster crop improvement. Extensive evidence amassed over many years has revealed that in higher eukaryotes, including plants, CO frequency per chromosome at each meiosis is generally low (1-3 COs per chromosome) and importantly, is non-uniform along chromosomes. As a result, in some species notably cereals such as wheat and barley, extensive regions, up to 70% of the physical length, of individual chromosomes rarely recombine. Hence, the challenge is to determine the factors that regulate CO frequency and localization in crops and to devise strategies to overcome this problem.
At the onset of meiotic prophase I the pairs of newly replicated sister-chromatids of each homolog become organized into linear looped-chromatin arrays conjoined at the loop bases by a proteinaceous axis. The homolog pairs then align and undergo synapsis through the formation of the synaptonemal complex (SC), a tripartite protein
structure comprising the homologous chromosome axes brought into close apposition by sequential polymerization of transverse filaments This extensive programmed chromosome remodeling is closely coordinated with, and inter-dependent on, homologous recombination (HR) which leads to the formation of COs.
Genetic studies and immuno-affinity proteomics using the model plant Arabidopsis thaliana, have enabled us to identify key proteins that comprise the meiotic chromosome axis. Recent studies show that proteins such as ASY1 and ASY3 are subject to post-translational modification by phosphorylation and we have mapped these sites. Initial analysis using site-directed mutagenesis of ASY1, indicate that phosphorylation has role in controlling axis function in relation to CO formation. In this project we aim to investigate this in further detail using Arabidopsis and extending the studies to wheat. Using immuno-affinity proteomics combined with immunocytochemistry we aim to study the temporal dynamics of phosphorylation of the chromosome axis and the influence of this on the repair fate of DNA double-strand breaks to form either COs or non-crossovers. Directed mutagenesis of phosphorylation sites will enable us to further explore how this modification influences repair fate.
- Ziolkowski PA, Underwood CJ, Lambing C, Martinez-Garcia M, Lawrence EJ, Ziolkowska L, Griffin C, Choi K, Franklin FC, Martienssen RA, Henderson IR. (2017) Natural variation and dosage of the HEI10 meiotic E3 ligase control Arabidopsis crossover recombination. Genes Dev. 31(3):306-317. doi: 10.1101/gad.295501.116. PMID: 28223312
- Lambing C, Franklin FC, Wang CR. (2017) Understanding and Manipulating Meiotic Recombination in Plants. Plant Physiol. 173(3):1530-1542. doi: 10.1104/pp.16.01530. PMID: 28108697
- Higgins JD, Perry RM, Barakate A, Ramsay L, Waugh, R, Halpin C, Armstrong, SJ and Franklin FCH (2012) Spatiotemporal Asymmetry of the Meiotic Program Underlie the Predominantly Distal Distribution of Meiotic Crossovers in Barley. The Plant Cell 2012 Oct;24 (10):4096-109. doi: 10.1105/tpc.112.102483. (BBSRC website feature: http://www.bbsrc.ac.uk/news/food-security/2012/121214-f-turning-up-heat-on-plant-sex.aspx
BBSRC Strategic Research Priority: Food Security
Techniques that will be undertaken during the project:
- Molecular cytogenetics/immunocytochemistry
- Advanced Light Microscopy - Super-resolution microscopy/imaging/image analysis
- Molecular biology and genetics/genetic analysis
Contact: Dr Eugenio Sanchez-Moran, School of Biosciences