At the heart of nature lies a tug-of-war for survival between hosts and pathogens. Within this complex struggle, immune systems have evolved specialised mechanisms. Our team, driven by a quest to harness these evolutionary products, delves into characterising these mechanisms at the molecular scale, primarily through the perspective of structural biology. This research aims to pave the way for biotechnological innovations.
The microbial world, constantly under siege from Mobile Genetic Elements (MGEs), has evolved refined defence arsenals. Central to our investigations are CRISPR-Cas systems. While most systems function in a role as a bacterial guardian, the universe of CRISPR systems have evolved an extensive array of strategies to protect the host from infection. Using cryo-electron microscopy, we investigated the molecular mechanisms of RNA targeting CRISPR-Cas systems to shed light on their function . This exploration has provided a better picture of the structural and functional dynamics of these systems and lays a foundation for their use as tools for RNA detection and editing.
Yet, the narrative is incomplete without acknowledging the adversaries. As bacteria strengthened their defences, phages, their persistent adversaries, adapt through sophisticated countermeasures. In collaboration with the Barr Lab, our team has successfully elucidated the structure of the tail spike depolymerase from Acinetobacter phage APK14, offering fresh insights into this evolutionary chess game and the potential for novel treatments for antibiotic-resistant bacterial infections.