3D organization of the mammalian genome

人类基因组计划为我们提供了人类基因组组成部分的完整DNA序列，但我们仍然对基因组如何被控制以表达人体不同细胞类型中正确的基因子集知之甚少。这一提议将首次评估整个基因组在特定细胞类型中的三维排列。最近的科学证据表明，基因组在细胞核空间内高度组织，以这样一种方式最大限度地有效表达所需或所需的基因子集，同时保持所有其他基因沉默。这从根本上改变了科学家对基因组和基因调控的看法。基因不是孤立地起作用，而是优先与其他类似调节的基因组合在一起，共同控制和有效表达。这一结果将对基因治疗和干细胞治疗等现代基因组药物产生根本性影响，并为健康和癌症等遗传疾病提供重要线索。这些知识对于确保未来的基因组和细胞疗法是安全、可靠的，并且是从知识和洞察力而不是试验和错误的角度来设计的至关重要。

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.