Modeling and bioinformatics of bacterial immune systems: understanding regulation of CRISPR/Cas and restriction-modification systems

Abstract

Bacterial immune systems protect bacterial cells from foreign DNA, such as viruses and plasmids. They also critically affect bacterial pathogenicity by reducing the flow of genes between bacteria. Two such major systems are restriction-modification and the recently discovered CRISPR/Cas systems. Here we review our work on understanding gene expression regulation in these systems, which takes a systems biology approach, combining modeling, bioinformatics and data analysis from quantitative experiments. Specifically, we address the following: (i) modeling gene expression regulation during restriction-modification system establishment in a naïve bacterial host, (ii) modeling the dynamics of CRISPR/Cas activation, in particular, how the features characterizing system transcription regulation and transcript processing affect the dynamics, (iii) predictions of transcription start sites for alternative s factors that have been poorly studied up-to-now, but are important as CRISPR/Cas likely responds to bacterial cell envelope stress, (iv) our preliminary results on predictions of different CRISPR/Cas components, in particular, small RNAs associated with the systems, which likely have a key role in their regulation.