3D organization of the mammalian genome

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The human genome project has given us the entire DNA sequence of building blocks of the human genome, but we still know little about how the genome is controlled to express the correct subsets of genes in the different cell types of the body. This proposal will assess for the first time the 3 dimensional arrangement of the entire genome in a particular cell type. Recent scientific evidence suggests that the genome is highly organized within the space of the cell nucleus in such a way as to maximize efficient expression of the desired or required subset of genes while keeping all of the other genes silent. This radically changes the way that scientist think about the genome and gene regulation in general. Genes are not functioning in isolation but preferentially grouping together with other similarly regulated genes to cooperate in their control and efficient expression. The results will have fundamental implications for modern genomic medicines such as gene therapy and stem cell therapies as well as give important clues to health and genetic diseases such as cancer. This knowledge is vitally important to ensure that future genomic and cell therapies are safe, reliable and designed from a position of knowledge and insight rather than trial and error.