Mission Statement

The cytoskeleton plays an essential role in the biology of all eukaryotic cells. This small set of dynamic protein polymer systems underpins the establishment and remodelling of long range cellular order, cell polarity, shape and division, and plays a critical role in control of the dynamic organisation of the internal membrane-bound compartments that distinguish eukaryotes from their prokaryotic ancestors. Until recently, the proteins that make up the eukaryotic cytoskeleton, which include actin, microtubules, ESCRTIII, Septins and coatamers, were thought to be unique to eukaryotes. While this view has been changing for some time, a revolution in our thinking came with the discovery of Lokiarchaeum ('Loki') and other members of the  'Asgard' clade of archaea through metagenomic sampling of ocean sediments in 2015. These are the closest living relatives of extant eukaryotes discovered so far.

 

Importantly, the composite genomes of Asgard archaea encode homologs of actin genes, actin-binding proteins, multiple ESCRT complex homologues, and tubulin. This makes it clear that the archaeal ancestor of eukaryotes probably already had a dynamic cytoskeleton. Excitingly, the Asgard genome assemblies also encode homologues of some of the key components of the membrane trafficking machinery in eukaryotes, including regulatory small GTPases and longin domains. Although none of these organisms has yet been isolated, observed under the microscope nor cultured, these genome sequences provide us with an unprecedented opportunity to explore the origins of these cytoskeletal elements and promise to shed light on the evolutionary transition that led to the emergence of eukaryotes.

 

To gain a better understanding of the evolutionary path by which these archaeal proteins gave rise to the eukaryotic cytoskeleton we have assembled a team of global experts in cytoskeletal biology and evolutionary cell biology. Our team includes Thijs Ettema, whose group discovered Loki; Ann-Christan Lindas, who was one of the first to show that ESCRTIII homologues play similar roles to their eukaryotic homologues in archaeal cell division; Jan Lowe and Ethan Garner, who have pioneered the ultrastructural, biophysical and biochemical understanding of the prokaryotic cytoskeleton; Ricardo Henriques, whose team has helped to drive recent advances in super-resolution microscopy; together with Mohan Balasubramanian and Buzz Baum, whose teams have helped to shape our understanding of the cytoskeleton and its roles in division across systems. With the generous support of the Wellcome Trust, our multidisciplinary team will explore the ultrastructure, biophysics and biochemical activities of cytoskeletal proteins encoded in Asgard genomes. In order to determine how the functional roles of these cytoskeletal systems might have changed during the transition from archaea to eukaryotes, they will also be carrying out a comparative analysis of cell division in archaea and eukaryotes.