Charlie Mo

Prokaryotic evolution is driven by two fundamental molecular mechanisms: horizontal gene transfer and mutagenesis. Horizontal gene transfer (HGT) involves the movement of large pieces of genetic material between cells and is mediated by mobile genetic elements (MGEs). Mutagenesis, by contrast, is the process during which small changes, such as insertions, deletions, or single base changes, are introduced into a cell’s genetic material. Most mutations are triggered by a variety of sources, including environmental stressors and so-called “pro-mutagenic” cellular processes. Both HGT and mutagenesis are major drivers of bacterial evolution and antimicrobial resistance.

In the recent years, the bacterial adaptive immune system, CRISPR-Cas, was shown to selectively target and eliminate MGEs, thus limiting the movement of genetic material between cells. We have demonstrated that CRISPR-Cas immunity against MGEs can also promote increased mutation rates inside bacteria, enabling them to adapt to stressors that they had not yet been exposed to. These findings raise the fundamental question of how bacteria evolve in the presence of immunity against MGEs. How does the activity of CRISPR-Cas and other defense systems shape genetic variation and bacterial adaptability over time? And conversely, how do variation and selective forces shape the activity of bacterial defense systems?

We focus our efforts on the following broad areas:

1. Examine how anti-phage defense systems, such as CRISPR-Cas, impact bacterial variation and evolution during active immunity

2. Investigate the mechanisms by which key cellular processes, such as transcription, modulate bacterial immunity

3. Study how variation and different selective pressures mold the activity of bacterial defense systems