Regulation of bacterial DNA transposition

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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: