− この都医学研セミナーは終了しました。 −
|演者||Justin M. O’Sullivaｎ博士（Liggins institute, University of Auckland, Grafton, Auckland 1032, New Zealand.）|
|世話人||正井 久雄 副所長（ゲノム動態プロジェクトリーダー）|
Genomes have evolved as three-dimensional structures. The spatial relationships formed between elements of these structures are captured by microscopy and proximity-ligation techniques. These spatial relationships reflect both the linear positions on the chromosomes and the nuclear functions that are active at the time of sampling. In silico modeling can help us understand these relationships by visualizing the emergent system architecture within an ensemble of structures that represent the possible solutions to the captured biological information. Modeling can also enable the investigation of the processes by which the biological system arrives at the final chromatin structure. Whereas a biological replicate captures the state at a single time-point, an effective model may be used to efficiently (both time and cost-effective) explain many different possible configurations over time, explaining the unique geometry of spatio-temporal regulation. Models can explain the effects of unique or rare combinations of genetic factors (i.e. personal genomic variations) without the need for repetition of in vivo experiments. Thus, architectural models of genomes will help elucidate how biological processes are coordinated within the nuclear environment
Here we will discuss the results of our efforts to model the emergent spatial architecture in Escherichia coli, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. Our models: 1) illustrate the importance of DNA knotting in bacterial cells; and 2) demonstrate how the spatial associations of elements can be employed to develop hypotheses about the regulation of nuclear processes.
Finally, we will discuss how the emergent spatial architecture in humans is captured within the context of common intergenic variation, explaining the association between noncoding genotypes and the risks of non-communicable disease. From model organisms to humans, we have leveraged in silico modeling of genomes to integrate the 3-dimensional organization of genomes, patterns of epigenetic modifications, and nuclear functions into an over-arching theory of the nucleus.