Associated organisationsHarvard University · Medical Research Council · Stockholm University · University College London · University of Uppsala · University of WarwickEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£2.8M
PeriodDec 2016 — Jul 2022
In plain English
AI plain-English summary
Every living cell—from a single archaeon to a human neuron—relies on an internal protein scaffold to hold its shape, move its contents, and divide. Yet scientists still do not understand the basic rules that govern how that scaffold is built or how it originated. This project tackles that gap by tracing the evolutionary history of the core structural proteins—actin, tubulin, and others—that were long thought to exist only in complex cells (eukaryotes) but have now been found in simple archaea. The team will use genetic sampling, super-resolution microscopy, and electron tomography to compare how these proteins organise space inside archaeal and eukaryotic cells. If successful, the work will reveal how the first internal compartments emerged in our distant ancestors, and uncover fundamental principles of cell architecture that remain hidden today. This is curiosity-driven fundamental science with no immediate practical application. However, understanding the basic logic of cell organisation could eventually inform efforts to engineer synthetic cells, target microbial pathogens, or treat diseases where cell shape and internal transport go wrong—areas where progress has stalled precisely because these core principles are unknown.
View original technical description
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.
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