Evolutionary Cell Biology of Archaea & Eukaryogenesis
Archaea are the third domain of life on Earth. They are present in most habitats, from the most extreme environments to the human gut, and it was recently proposed that eukaryotes originated from within the archaeal domain. However, very little is known about their cell biology.
A major barrier to the advancement of archaeal cell biology has been the inability to image model species, which are all extremophiles, in physiological conditions. For example, the model crenarchaeon Sulfolobus acidocaldarius optimally grows at 76°C and pH 2. In the lab, we develop new tools to allow quantitative imaging of extremophiles. We also use biochemical, structural, genetic and bioinformatic approaches to study fundamental aspects of archaeal cell biology in various archaeal models.
One of the most puzzling events in cellular evolution is eukaryogenesis. Thought to have appeared ~2.2 Gya, the first eukaryotes resulted from the association between an archaeon and a bacterium, with the latter giving rise to modern mitochondria. However, this model is still incomplete, and the cellular and molecular aspects of eukaryogenesis are still unclear. In particular, key questions remain regarding the cellular complexity of the first eukaryotic common ancestor. Our lack of understanding of the basic cell biology of archaea is a major hurdle to answering these questions.
Current projects
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Chromosome segregation
In eukaryotes and bacteria, chromosome segregation relies on intracellular systems that move chromosomes in opposite directions (such as the microtubule spindle in eukaryotes or the ParABs system in rod-shaped bacteria). In archaea, the mechanisms of chromosome segregation are still poorly understood. The only known system, called SegABs, was discovered in Saccharolobus solfataricus. While SegA is a bacterial-type ParA-like ATPase, SegB is a conserved DNA-binding protein unique to archaea.
In the lab, we use structural biology, biochemistry, bioinformatics and quantitative fixed and live-cell imaging to study the cellular and molecular mechanisms and the evolution of the archaeal SegABs system. Since our model organism Sulfolobus acidocaldarius is genetically tractable, we can test all our hypotheses in vivo.
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Evolution of the actin cytoskeleton
One hallmark of eukaryotic cells is a dynamic, multifunctional actin cytoskeleton. In bacteria, actin-like proteins like ParM and MreB assemble filaments that assume one specific cellular function with little to no regulatory proteins. In sharp contrast, eukaryotic actins assemble a conserved filament that fulfills multiple functions dictated by a great number of regulatory proteins. Recent findings in Asgard archaea suggest that the shift from a bacterial- to eukaryote-like actin cytoskeleton occurred in archaea. For example, crenactin was shown to possess multiple regulatory proteins in Pyrobaculum calidifontis.
In the lab, we use biochemistry, single molecule imaging and bioinformatics to study the functions and regulation of archaeal actins, their role in eukaryogenesis, and the emergence of the eukaryotic-like actin cytoskeleton. We are also developing genetics in new model organims.