Identifying principles and mechanisms of cell cycle control in Bacteroides species.

ongoing

The gut hosts a complex community of bacteria, archaea, and viruses, which together play a key role in shaping human health. The microbiome has featured in extensive metagenomic studies, uncovering tremendous diversity. However, there is remarkably little research on the cell biology of the microbiome’s constituent members. Among the most influential members of the gut microbiome is the genus Bacteroides, which has been implicated in digesting complex carbohydrates, maturation and regulation of the immune system, and regulating intestinal neurotransmitters. There is also significant interest in engineering Bacteroides spp. as promising candidates for diagnostic and therapeutic purposes. Despite their clear relevance for human health, we lack knowledge on fundamental aspects of Bacteroides proliferation (i.e., their cellular organisation, mechanisms underlying their growth, cell division, DNA replication, or their growth preferences). Such information is essential and represents previously unexplored bacterial cell biology, given Bacteroides must adapt to an incredibly transient environment that shifts rapidly from feast to famine while contending with a constant stream of variable stressors. This project seeks to advance our knowledge of Bacteroides spp. by examining intraspecific diversity, utilising tractable Bacteroides strains, and leveraging the Gover’s lab high-throughput single cell phenomics (HTSCP) methodology. I hypothesise that Bacteroides spp. utilise simple rules of cell cycle control, similar to those recently identified in Escherichia coli by Govers et al., to ensure robust cellular replication across many conditions. Such unifying principles integrate cell cycle and growth rate with cell size, while enabling plasticity, allowing cells to respond to their environments. Understanding these rules and identifying their underlying mechanisms will provide indispensable information for furthering studies of the Bacteroides and developing their utility.