Cell cycle control in archaea

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All life on earth can be divided up into three domains, eubacteria, archaea and eukaryotes (plants, animals, fungi etc). While eubacteria and archaeal cells tend to be small and to be simple in organisation, almost all eukaryote cells are large and share an extraordinarily complex internal architecture. Maintaining this order as cells grow and divide requires an elaborate set of molecular machines. Much of the core "cell division cycle" machinery involved in coordinating cell growth and division in complex eukaryotic cells was identified in pioneering genetic studies in the 1970s by Lee Hartwell and Paul Nurse. This knowledge now underpins much of biomedicine, from cancer, where the control of cell division goes awry, to regenerative medicine.Until very recently it was not clear how complex eukaryotic cells might have arisen. Now, however, as the result of surveys of different environments to identify the genomes of organisms that can't be cultivated using metagenomic sequencing, it has become clear that many of the machines that function to maintain the dynamic internal organisation of eukaryote cells have their origins in archaea. An improved understanding of the origins of eukaryotes therefore requires a better understanding of archaeal cell biology - more specifically studies in TACK/Loki-family archaea to which we are most closely related. Currently, far and away the best model system in which to carry out experimental research into our archaeal origins is Sulfolobus (a member of the TACK-family archaea). Importantly, Sulfolobus has a cell division cycle that seems to be ordered in a similar way to the eukaryotic cell cycle. However, little is known about the molecular machinery involved in its regulation. This is both because of the paucity of research in archaea, and the difficulties of doing cell biology in a small extremophile. We aim to change this. As the result of the recent development of Sulfolobus molecular genetics, cheap whole genomic sequencing (enabling mutant genes to be cloned) and the development of super-resolution microscopy (which enables these small cells to be imaged using light) now is the perfect time to use Sulfolobus as an experimental model to determine how the archaea cell division cycle is structured and to identify the molecular machines involved in its regulation. This will enable us to determine for example whether archaea have a cell cycle clock like that found in eukaryotes and checkpoints like those used to couple DNA replication to cell division in eukaryotes.By doing so we expect to learn much about this understudied domain of life of earth. In addition, we expect this work to give us a better understanding of our origins, and of the function of the eukaryotic cell division cycle, which plays such an important role in human development, homeostasis and disease.