Supervisor
Professor Ian Henderson
Brief summary
Ian Henderson is Professor of Genetics and Epigenetics in the Department of Plant Sciences. His group study plant genomes, with a focus on epigenetics and meiosis. They have pioneered study of meiotic recombination using genomics in the model plant Arabidopsis, and harnessed forward and reverse genetics to identify multiple loci that control recombination. In 2021, the Henderson group used Oxford Nanopore sequencing to publish a breakthrough assembly of the Arabidopsis centromeres (Naish et al 2021 Science). This was followed by analysis of Arabidopsis pancentromeric diversity (Wlodzimierz et al 2023 Nature), which has led to new understanding of centromere structure, function, and evolution.
The proposed work builds on these advances to functionally study the Arabidopsis centromeres using CRISPR/Cas9. The student will functionally explore the genetic and epigenetic organisation of the Arabidopsis centromeres to understand their function. This will include use of CRISPR-mediated editing of the centromere satellite repeats and long read Nanopore sequencing to define how structural change influences epigenetic status and chromosome conformation. They will combine lines with changed centromeres with fluorescent reporters that measure Mendelian transmission, to test the model that centromere competition can drive rapid evolution. Together, the project will provide the student with a comprehensive training in functional genomics, using new tools such as CRISPR and long-read sequencing to interrogate complex yet fundamental regions of plant genomes.
To translate knowledge of plant genomes, the Henderson group collaborates with plant industrial bioscience, including Bayer Biosciences and Solynta, where we aim to control recombination in crops and accelerate breeding.
Project Summary
Centromeres are critical for cell division, loading CENH3/CENPA histone variant nucleosomes, directing kinetochore formation, and allowing chromosome segregation. Despite their conserved function, centromere size and structure are highly diverse across species, which is termed the ‘centromere paradox’. However, the mechanisms of centromere sequence change, and the evolutionary drivers are unclear. We have recently assembled the Arabidopsis thaliana pan-centromere, which has revealed extreme intra-species diversity, where the satellite repeats have undergone extensive recombination and concerted evolution.
Additionally, the satellite repeat arrays have been invaded by centrophilic ATHILA retrotransposons. Building on the Arabidopsis pancentromere, the student will functionally explore the genetic and epigenetic organisation of the Arabidopsis centromeres to understand their function and unique evolutionary biology. This will include use of CRISPR-mediated editing of the centromere satellite repeats and use long read Nanopore sequencing to define how structural change influences cell division, epigenetic status and chromosome conformation. They will combine lines with changed centromere satellite with fluorescent reporters that measure Mendelian transmission of centromeres, to test the model that centromere drive can provide a selective pressure for rapid evolution. This project will take genetic and epigenetic approaches to understand centromere function and evolution, which has fundamental relevance for eukaryotic genomes. Together, the project will provide the student with a comprehensive and cutting-edge training in functional genomics, using new tools such as CRISPR and long-read sequencing to interrogate complex yet fundamental regions of plant genomes.
What will the successful applicant do?
The student will functionally explore the genetic and epigenetic organisation of the Arabidopsis centromeres to understand their function. This will include use of CRISPR-mediated editing of the centromere satellite repeats and long read Nanopore sequencing to define how structural change influences epigenetic status and chromosome conformation. They will combine lines with changed centromeres with fluorescent reporters that measure Mendelian transmission, to test the model that centromere competition can drive rapid evolution. Together, the project will provide the student with a comprehensive training in functional genomics, using new tools such as CRISPR and long-read sequencing to interrogate complex yet fundamental regions of plant genomes.
References
Wlodzimierez, P, Rabanal, F., Burns, R., Naish, M., Primetis, E., Scott, A., Mandakova, T., Gorringe, N., Tock, A.J., Holland, D., Fritschi, K., Habring, A., Lanz, C., Patel, C., Schlegel, T., Collenberg, M., Mielke, M., Nordborg, M., Roux, F., Shirsekar, G., Alonso-Blanco, C., Lysak, M.A., Novikova, P., Bousios, A.W., Weigel, D.W. and Henderson, I.R. (2023) Cycles of satellite and retrotransposon evolution in Arabidopsis centromeres. Nature doi:10.1038/s41586-023-06062-z (0)
Naish, M., Alonge, M., Wlodzimierez, P., Tock, A., Abramson, B., Schmucker, A., Mandakova, T., Bhagyshree, J., Lambing, C., Kuo, P., Yelina, N., Hartwick, N., Colt, K., Smith. L., Ton, J., Kakutani, K., Martienssen, R., Schneeberger, K., Lysak, M., Berger, F., Bousios, A., Michael, T., Schatz, M. and Henderson, I.R. (2021) The genetic and epigenetic landscape of the Arabidopsis centromeres. Science eabi7489 (100)