MECHANISMS & REGULATION OF GENE EXPRESSION

机制

基本信息

批准号：
3563666
负责人：
PAUL BERG
金额：
$ 44.27万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1975
资助国家：
美国
起止时间：
1975-09-01 至 1992-06-30
项目状态：
已结题

项目摘要

The advent and widespread application of the recombinant DNA methodology during the past twelve years has greatly extended our understanding of the molecular basis of heredity. More significantly, the emergence of a new molecular paradigm - reverse genetics, which relies on the ability to specifically modify the structure of genes in vitro and to test their biological properties, has revolutionized the experimental approaches in molecular genetics. The ability to construct minichromosomes with novel arrangements of genetic elements also provides vectors for the isolation of genes as well as substrates for the analysis of specific genetic reactions. Our proposal, which applies this approach to explore the basic mechanisms of gene regulation in the establishment of immune responsiveness and of genetic recombination, aims (1) identify the factors and mechanisms that limit the epression of antibody genes to only lymphoid cells; (2) isolate and characterize the human gene whose dysfunction is responsible for galactosemia; (3) understand the mechanisms responsible for non- homologous, homologous and non-reciprocal modes of genetic recombination, especially those which permit the rejoining of broken DNA; (4) develop genetic approaches to effect a replacement or repair of chromosomal DNA sequences; (5) developing vectors which can deliver genes to only specific types of cells. It is anticipated that the information we develop will advance our unerstanding of the molecular basis of disease and provide novel approaches to their prevention, treatment and cure.

重组DNA的出现和广泛应用过去十二年的方法论已经大大扩展我们对遗传的分子基础的理解。更多的值得注意的是，一种新的分子范式的出现—— 反向遗传学，依赖于特异性修饰的能力体外基因结构并测试其生物学性质，彻底改变了实验方法分子遗传学。构建微型染色体的能力遗传元件的新颖排列还提供了用于分离基因的载体以及基因的底物特定遗传反应的分析。我们的建议适用这种方法探索基因调控的基本机制建立免疫反应和遗传重组、目标 (1) 找出限制因素和机制仅对淋巴细胞表达抗体基因； (2) 分离并表征人类基因功能障碍是半乳糖血症的原因； (3) 了解造成非正常现象的机制同源、同源和非互易模式基因重组，特别是那些允许断裂DNA的重新连接； (4) 开发遗传方法来实现替代或修复染色体DNA序列； (5) 开发能够将基因仅传递给特定类型的细胞。预计我们开发的信息将推进我们的了解疾病的分子基础并提供新的预防、治疗和治愈的方法。