Understanding cellular organisation: from archaea to eukaryotes (360G-Wellcome-203276_B_16_Z)

We know surprisingly little about the basic logic, topology or origins of eukaryotic cell architecture even though such an understanding is fundamental to most biomedical research. Until recently, the proteins responsible for shaping eukaryotic cells (including Actin/Tubulin/coatamers/ESCRTIII) were thought to be unique to eukaryotes. This changed with the discovery of close homologues in TACK/Loki-family archaea. Despite the important part played by these proteins during eukaryogenesis, we know little about their functions in the context of archaea. To determine how these cytoskeletal systems with origins in archaea contributed to the emergence of internal compartments that define eukaryotes, our team will use metagenomic sampling and phylogenomics to trace their evolutionary history, and a combination of approaches, including live super-resolution microscopy and electron tomography to carry out a comparative analysis of their ultrastructure, dynamics and function in both archaea and eukaryotes. Ultimately, we expect this evolutionary cell biological analysis to make a start towards an understanding of archaeal cell biology, to reveal the likely path of eukaryogenesis, and to reveal underlying principles of eukaryotic cell biology that so far have eluded us. In doing so, we expect this fundamental research to have a signficant impact in the future on human health and disease.