ECoToL · Deciphering the molecular mechanism of Eleos, a conserved immune system across the tree of life

Sensing viral infections and mounting a response is crucial for all domains of life. Many immune mechanisms in higher eukaryotes were thought to be evolutionary innovations, but recent research reveals that some components of the innate immune system have evolved from bacterial genes. Eleos, a novel anti-viral system in prokaryotes, shares similarities with eukaryotic GIMAPs (GTPase immunity-associated proteins), yet their evolutionary history and anti-viral mechanisms remain unknown.ECoToL's objectives are threefold:1.Identify Eleos systems, study their architecture, and determine their distribution in bacteria.2.Explore the molecular mechanism by which bacterial Eleos confers resistance against phages.3.Investigate when and how Eleos was acquired in eukaryotes, assess its distribution, and examine the conservation of the mechanism in eukaryotes.We will analyze large genome datasets to trace Eleos system evolution across different life domains. Additionally, we will identify phages Eleos defends against and the mechanisms by which phages evade this defense. Biochemical, biophysical, and structural biology methods will illuminate the molecular mechanisms in bacterial Eleos. Further genomic analysis and experimental methods will answer whether this mechanism is conserved in higher eukaryotes.ECoToL is a multidisciplinary project pioneering comparative immunology between prokaryotes and eukaryotes. This innovative concept aims to enhance our understanding of immune systems, which is critical for staying ahead of viral threats, improving viral infection treatments, reducing viral resistance, and enhancing global health security.