Regulation of bacterial DNA transposition

转座子是移动的遗传元件，几乎在所有生物体中发现。它们通过介导多种类型的基因重排和影响邻近基因的表达来影响宿主。一般来说，转座子通过影响转座酶表达的系统受到严格的负调控，转座酶是介导转座反应中DNA链切割和连接步骤的蛋白质。限制转座子移动减少了转座子对其宿主造成的诱变负担。然而，有充分的证据表明，保持低水平的转座频率可以使宿主受益，因为转座产生的遗传多样性可以帮助生物体适应不断变化的环境条件。此外，还有一些例子，转座子已经被它们的宿主“驯化”，使得转座子编码的蛋白质通过承担重要的细胞功能而对宿主做出贡献。我们的研究计划的目标是探索转座子和它们的宿主之间的互惠关系，目的是利用这些知识来操纵基因组进行基因工程。这五年期间的具体目标是：

Transposons are mobile genetic elements found in virtually all organisms. They impact their hosts by mediating numerous types of genetic rearrangements and by influencing the expression of neighboring genes. In general transposons are tightly negatively regulated through systems that impact on the expression of transposase, the protein that mediates DNA strand cutting and joining steps in transposition reactions. Limiting transposon mobilization reduces the mutagenic burden transposons inflict on their hosts. However, there is ample evidence that maintaining transposition frequencies at low levels can benefit the host as the genetic diversity generated by transposition can help an organism adapt to changing environmental conditions. In addition, there are a few examples where transposons have been ‘domesticated’ by their hosts such that a transposon-encoded protein contributes to the host by taking on an important cellular function. The goal of our research program is to explore the mutualistic relationship between transposons and their hosts with the intent of using this knowledge to manipulate genomes for genetic engineering purposes. Specific objectives for this 5 year period are: