The discovery of the DNA double helical structure marked the beginning of modern molecular biology. If DNA sequencing is the blueprint of life, the spatial organization of DNA is the operating manual: it controls gene expression, DNA replication, repair, and recombination. Defective DNA organization can alter cellular behavior and is a hallmark of aging and multiple diseases including cancer, progeria, among others.
Unfortunately, relatively little is known
about the three-dimensional (3D) organization of DNA beyond the length scale of
the nucleosomes, in large part due to the lack of tools that allow direct
visualization and comprehensive mapping of the 3D organization of DNA in
individual chromosomes. Siyuan Wang, an Assistant Professor in the Department
of Genetics and the Department of Cell Biology of the Yale School of Medicine
at Yale University, is helping to solve this problem.
He developed a highly multiplexed DNA imaging method, via sequential fluorescence in situ hybridization. This novel method enabled direct spatial tracing of numerous genomic regions in individual chromosomes in single cells, offering a powerful tool to study the 3D organization of DNA. This work opened up many opportunities to study the spatial organization of DNA at different length scales in a variety of important biological processes and diseases.
His current work, which helps explain the complexity and diversity of DNA organization within and among cells, can further unveil how DNA organization controls genomic functions; from the regulation of gene expression to the replication of the genome. It can also elucidate how DNA organization varies in different tissues and evolves in development, aging, and diseases, and can lead to novel diagnostic and treatment strategies.