The division of the cellular living world into three domains, Archaea, Bacteria and Eukarya, has opened a new perspective for the exploration of the microbial world and for evolutionary studies. To complete the inventory of living organisms, we are studying viruses from hyperthermophilic archaea that represent the less studied component of the biosphere. Their virions exhibit unique morphotypes and most of their genes encode unknown proteins.

We are now actively studying the mechanisms for DNA replication and transcription of several of these viruses and we have started to investigate more precisely host-virus relationships. We collaborate with external laboratories for structural genomic projects and to explore the potential of archaeal viruses in nanotechnology. We have recently discovered a completely new mechanism for the exit of virion that involves the formation of unusual pyramid-like structures that produce holes in the cell surface (Figure). This illustrates how the infected cell is tranformed into a virion factory. We thus propose to consider the infected cells as the living form of viruses.

Our interest for microbial viruses has also led us to initiate a new project on phage therapy. Several new viruses infecting pathogenic bacteria have been isolated and a mouse model has been successfully tested to help establishing rational approaches for phage therapy. In order to stimulate common thinking and collaboration between scientists working on viruses infecting either bacteria, archaea or protists, we have organized in 2010 at the Institut Pasteur the first international meeting on viruses of microbes. This meeting was attended by more than 400 participants.

In parallel to experimental studies, we pursue several in silicoresearch projects to tackle fundamental questions dealing with microbial diversity and evolution. Last year, we have identified in silicoand confirmed experimentally dif sites in archaeal genomes (site used for the resolution of dimeric chromosomes).

We have established a robust reference phylogeny of the archaeal domain, which has led to the proposal of a new phylum, the Thaumarchaea.

We have also performed several phylogenomic analyses to understand the evolution of major molecular complexes and cellular processesin the three domains of life. We are especially interested by the relationships between Archaea and Eukarya and the origin of eukaryotes. In line with our interest for viruses and related elements, we are also studying the impact of viruses and plasmids (VP) on genome evolution and how the transfer of genes between VP and cells affect molecular phylogenies.

Keywords: Archaea, viruses, genomics, Replication, Transcription, Molecular phylogeny, Evolution, Phage therapy

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