Video interview of Patrick Forterre : Microbiology in CNRS
My first research interest was in DNA replication at the exciting time (early seventies) when biochemists were looking for the true replicase in Escherichia coli and discovered new unexpected functions involved in DNA metabolism. I fell in love with DNA gyrase, a fascinating enzyme that produces DNA superhelices, and proposed a model explaining the action of this enzyme via a double-stranded DNA break. Half of the model (rotation of the enzyme on itself) turned out to be wrong, but it was a lot of fun.
In 1982, reading the review papers on Archaebacteria (now renamed Archaea) by Carl Woese in Scientific American, I decided to work on enzymes that manipulate DNA superhelices (called DNA topoisomerases) in these unique microbes, the third form of life on earth. The original question was : do Archaea possess a gyrase activity, as classical bacteria, or an enzyme which can only eliminate superhelices (relaxing enzyme), like all eucaryotic organisms (including ourselves) ? It turned out that hyperthermophilic archaea actually contained a reverse gyrase, i.e. an enzyme which produces superhelices (called positive) winding in the opposite direction from those (negative) produced by classical gyrase. Positive superhelices have an increasing number of topological links between the two DNA strands, and this might counteract the effect of temperature increasing on DNA structure, such as partial separation (unwinding) of the two strands or change in the helix path (but this has yet to be definitely proven).
From that time (1984), I have been working on reverse gyrase in collaboration with Michel Duguet. In 1986, we discovered that the DNA of a virus from a hyperthermophilic archaea indeed exhibits a positive superhelix. Later on, we shown that reverse gyrase is present in all hyperthermophiles, either Archaea or Bacteria. More recently, we have shown that reverse gyrase is formed by the fusion of two proteins: an energy consuming enzyme (ATPase) that ressembles helicases (enzymes which separate the two strands of the DNA helix) and a DNA relaxing enzyme. In my opinion, the composite origin of reverse gyrase and its extreme sophistication argue against the primitivness of hyperthermophilic microbes.
My initial work on Archaea was made possible by encouragments and biological material provided by Wolfram Zillig. His invitation at the second archaebacterial meeting held in Munich in 1985 was a decisive step in my scientific career. The same year, I joined the laboratory of Anne-Marie De Recondo in Villejuif to lead a small research group working on Archaea. She provided me with the unique opportunity to work freely on my own ideas and to finally defend my "Thèse d'état" in a favorable context. My former student Christiane Elie was on my side from the beginning of this adventure. We discovered the inhibition of archaeal DNA replication by the eucaryotic inhibitor aphidicolin and later on, in Villejuif, she purified and characterized two DNA polymerases from thermoacidophilic archaea, while another pHD student, Mouldy Sioud, discovered that Archaea are sensitive to antitumoral drugs active against human DNA topoisomerases.
In 1988, I was invited by Andre Berkaloff to set up my own laboratory at the Institut of Microbiology in Orsay (south of Paris). We pursued our work on DNA gyrases and relaxing enzymes (all of them called DNA topoisomerases) and on DNA polymerases, while extending our investigations on various aspects of DNA metabolism in both hyperthermophilic bacteria and Archaea. A former PhD student, Franck Charbonnier, and a post doc, Purificacion Lopez-Garcia analyzed DNA from hyperthermophilic archaea and showned that not only viral DNA but also cellular DNA have higher number of links between the two strands, compared to organisms living at "normal" temperatures. I have been involved myself in a study performed by Evelyne Marguet on the effects of very high temperatures on the DNA molecule.
A spectacular and recent achievement of our work on DNA topoisomerases was the discovery by Agnes Bergerat and Danielle Gadelle of a completely new family of these enzymes in Archaea, leading to the identification of the protein which initiates the first step of meiotic recombination in eucaryotes (breakage of one of the two parental chromosomes).
Our installation in Orsay also allows us to initiate new research projects. In particular, we also started to work on anaerobes. Yvan Zivanovic established the culture conditions for Pyrococcus and related species and initiated a research project towards the construction of genetic tools for these microbes (in the frame of a EC Biotech program). This work was boosted by our collaboraton with Daniel Prieur via the GDR Bactocean (Groupement De Recherche CNRS/IFREMER) that led to the identification and characterization of the first plasmid from hyperthermophilic archaea. We also help the IFREMER group working on hyperthermophiles in Brest to start a research project on the characterization of new hyperthermophilic DNA polymerases.
In recent years too, Bernard Labedan set up in our lab a research group on molecular phylogeny and protein evolution. He became our advisor in tree construction and initiated his own work programm on bacterial genome evolution.
In February 1996, we organized the first francophone meeting on the molecular biology of thermophiles at Gif sur Yvette, in the South of Paris. More than 80 scientists attended the meeting, a strong indication that this field of research is expending in the francophone community.
Personnally, I have been more and more involved in intense debates about the hot origin of life hypothesis and rooting of the tree of life. Thanks to André Brack and André Adoutte, I got in touch with the scientific community working on the origin of life and molecular evolution, respectively. I have tried to challenge some of the new dogma in these fields, not yet with great success. In 1996, I co-organized the first meeting on the last common ancestor and beyond (thanks to the Fondation des Treilles) with the aim to boost researches in this particular area.
Means In French Only
Version Française de ma page
My CV can be found here.
You may also read an abstract of the lecture I gave at the 11th International Conference on the Origine of Life, July 7-12 Orléans, France
Another abstract of a lecture at the "First Internationnal Congress on Hyperthermophiles ", held in Estoril 2-6 June 96, Portugal.
Also a short article: Les Origines de la vie, Nouveaux Concepts, Nouvelles Questions gives a general viewpoint about the various issues of the origin of life problem.
La Fondations des Treilles Meeting proceedings, held in Les Treilles (France), july 18-24, 1996 : LUCA, the Last Universal Common Ancestor, as reported by P. Forterre.