The Work of Simon Chan
Simon Chan studied the fundamental biology of genetic inheritance with the aim to manipulate it for practical benefit. Centromeres enable chromosome segregation during cell division because they attach to spindle microtubules via a connector called the kinetochore complex. The centromere is epigenetically specified by CENH3, a protein required to bridge DNA to kinetochore connection.
Using the model plant Arabidopsis thaliana Simon's laboratory discovered that centromere differences between two parents can cause one parental genome to be selectively eliminated when their genomes meet to form the embryo. When Arabidopsis plants expressing altered CENH3 proteins are crossed to wild type, chromosomes from the mutant parent are lost, yielding haploid progeny. This finding prompted Simon to pursue both basic and applied studies with the following objectives.
- Facilitate rapid mapping of plants traits. The Chan laboratory and collaborators demonstrated the use of CENH3-mediate haploid induction for very fast genetic analysis: what that would normally take 7 or 8 generations could be condensed in a single generation through a method that produces double haploids from an F1 hybrid1.
- Provide high yield hybrid seed without the complicated process of hybrid production. Farmers in developed countries can purchase expensive hybrid seed and enjoy its yield and stress tolerance advantage. Traditionally produced hybrid seed, however, cannot be made affordable in developing countries. Simon and collaborators demonstrated a first important step toward simple hybrid seed generation featuring the haploid induction technology.
- Develop new plant breeding methods through chromosomal content engineering, also referred to as "reverse breeding". In collaboration other labs, Simon showed that CENH3-manipulation could be used to rapidly produce multiple characterized combinations of paternal and maternal chromosomes.
- Understand the mechanistic basis of centromere evolution, genome elimination, and haploid-induced chromosome rearrangements.
Simon's work is now continued by his laboratory members and collaborators.
1. Seymour, D. K. et al. Rapid creation of Arabidopsis doubled haploid lines for quantitative trait locus mapping. Proc Natl Acad Sci U S A (2012).
2. Marimuthu, M. P. et al. Synthetic clonal reproduction through seeds. Science 331, 876 (2011).
3. Wijnker, E. et al. Reverse breeding in Arabidopsis thaliana generates homozygous parental lines from a heterozygous plant. Nat Genet 44, 467-470 (2012).
4. Ravi, M. & Chan, S. W. Haploid plants produced by centromere-mediated genome elimination. Nature 464, 615-618 (2010).
5. Ravi, M. et al. The rapidly evolving centromere-specific histone has stringent functional requirements in Arabidopsis thaliana. Genetics 186, 461-471 (2010).
6. Ravi, M. et al. Meiosis-specific loading of the centromere-specific histone CENH3 in Arabidopsis thaliana. PLoS Genet 7, e1002121 (2011).
7. Melters, D. P., Paliulis, L. V., Korf, I. F. & Chan, S. W. Holocentric chromosomes: convergent evolution, meiotic adaptations, and genomic analysis. Chromosome Res 20, 579-593 (2012).