3D organization of the mammalian genome

人类基因组计划已经为我们提供了人类基因组的整个DNA序列，但我们仍然对基因组是如何控制的，以在身体的不同细胞类型中表达正确的基因亚集知之甚少。这项提议将首次评估特定细胞类型中整个基因组的三维排列。最近的科学证据表明，基因组在细胞核的空间内以一种方式高度组织，以最大限度地有效表达所需的或所需的基因子集，同时保持所有其他基因的沉默。这从根本上改变了科学家对基因组和基因调控的总体看法。基因并不是孤立地发挥作用，而是优先与其他类似调控的基因组合在一起，以协调它们的控制和有效表达。这一结果将对基因疗法和干细胞疗法等现代基因组药物产生根本影响，并为研究癌症等健康和遗传性疾病提供重要线索。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，并从知识和洞察力而不是试验和错误的立场进行设计至关重要。

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.