Rings and Clamps around DNA in Asgard Archaeal cells: Insights into DNA replication and repair from our closest prokaryotic ancestors


Dr Laura Spagnolo, School of Molecular Biosciences (University of Glasgow) 

Dr Nick Robinson, Biomedical And Life Sciences (Lancaster University) 



The very recent discovery of Asgard archaea led to a paradigm shift in evolutionary biology: their molecular similarity to eukaryotes is so close that the hypothesis arose that eukaryotes emerged directly from one of the Asgard lineages. DNA replication is a hallmark of living organism and as such has undergone intense biological investigation. Cryo-EM has played an important role in our current understanding of the eukaryotic DNA replication mechanism, in particular with respect to the highly dynamic replicative helicases.

The Spagnolo lab (Glasgow) has worked on the cryo-EM studies of the helicase from the archaeon Pyrococcus abyssi for some time, contributing to the characterisation of its structural polymorphism. Joining expertise with the Robinson group (Lancaster), who has long-standing expertise in the biochemistry and molecular biology of archaeal systems, including the replicative machinery and recent work on Asgard archaea, we are now setting out to study the MCM helicase from the recently isolated Asgard archaeon Candidatus Prometheoarchaeum syntrophicum and that from the thermophilic species Candidatus Odinarchaeum yellowstonii. Our structural and biochemical analyses will shed light on the fine molecular details of one of the paramount biological processes, DNA replication, at the interface between archaea and eukaryotes.

The anticipating training outcomes will be proficiency in the preparation and characterization of macromolecular complexes, as well as training in cryo-EM from grid preparation to structural determination and interpretation.