On June 9, 2025, at 4pm our grad student Sofia Nicole Smith will defend her Master’s thesis entitled “Investigating How Genomic Context and Regulatory Elements Impact IS1 Transposition within the Escherichia coli Genome.”

Abstract

Insertion sequences (IS elements) are key drivers of bacterial genome plasticity, yet the regulation of their transposition remains poorly understood, even as their relevance grows due to connections with CRISPR/Cas9 systems and gene therapy applications. This study characterizes the internal, host, and genomic factors that regulate IS1 transposition at the donor site. Mutations within the IS1 coding region significantly reduce, but do not abolish, transposition. Inducing a ribosomal -1 frameshift at the poly A-tract increases transposition over 100-fold; however, this enhancement is largely reversed by restoring InsA-mediated transcriptional regulation. This study begins to characterize the nature with which disruptions of flanking genomic regions modulate transposition, a phenomenon that remains very understudied. The effects shown here underscore the importance of genomic context. Finally, IS1 primarily undergoes replicative transposition, a mechanism shown here to be independent of transposase levels in the cell. These findings contribute to our understanding of mobile genetic element regulation and potentially offer strategies for mitigating their potentially harmful effects.