9th EMBL/EMBO Joint Conference 2008
Antoine Danchin, Institut Pasteur, France
A mathematician and a physicist, Antoine Danchin shifted to experimental microbiology in the early seventies. The goal of his research has always been to try and understand how genes display a collectively behaviour. To this aim, Antoine Danchin initiated in 1985 a collaboration with computer scientists for evaluation of artificial intelligence techniques to the study of integrated problems in molecular genetics. This convinced him that it was time to investigate genomes as wholes, provided that an important effort in computer sciences was initiated in parallel. Early in 1987 he proposed that a sequencing program should be undertaken for Bacillus subtilis. This proposal was actualised by an European joint effort on this genome, starting in 1988, supported by Japan from 1990 and completed in 1997.
The first significant and unexpected discovery of this work was, in 1991, that many genes (at the time, half of the genes) were of completely unknown function. As a further outcome of this work, it has been discovered that genomes are structures that are much more orderly than previously suspected, and that there exists a correlation between the organisation of the genes in the genome and the cell's architecture. Antoine Danchin has published more than 300 scientific articles and more than 200 articles in the domain of epistemology, ethics and popularisation of science. He has also published four books, including a book on the origin of life, and a book on genomes (The Delphic Boat, Harvard University Press, 2003). He has a continuous interest in philosophy, and in exchanges with other civilisations (creation of a Chinese-European University Without Walls in 1990).
This was at the root of his interest to promote genome research in Hong Kong, where he stayed for three years, creating the HKU-Pasteur Research Centre in 2000. Research director at the CNRS and heading a research Unit (Genetics of Bacterial Genomes) at the Institut Pasteur in Paris, he is the director of the Department Genomes and Genetics at this Institute.
Life and perpetuation of life of a synthetic bacterium
Biology began with inventories: organisms, cells and finally molecules. Placing biology within information sciences, molecular biology introduced recursivity via the genetic code. Yet, biology remained an organised catalogue of isolated parts and processes. Synthetic biology reconstructs the "cell factory" to investigate whether some essential missing entity remains to be uncovered. The engineering view combines nuts and bolts - biobricks - to construct synthetic cells by rational design. The cell as a computer-makingcomputers model uncovers rules permitting this feat, not yet achieved by authentic computers. In computers, the data/program is physically separated from the machine. In cells, physical separation of the genetic program is established: DNA transplantation changed a bacterial species into another one. Cell duplication combines reproduction of the machine and replication of the program. While reproduction can improve over time, replication accumulates errors. Yet, while all organisms age, they give birth to young ones: some ubiquitous process, when reproducing the cell machine, accumulates information.
To identify the relevant functions w e looked for genes which persist in genomes. Genomes are organised as two gene sets: a paleome (dating from the origin of life), and a cenome (permitting life-in-context). The paleome comprises twice as many genes as those expected to make a synthetic cell. The unexpected half comprises a counter-intuitive category of genes coding for energy-dependent degradative processes (degradation produces energy, rather than uses it). Information theories show that, contrary to intuition, creation of information is reversible. Yet, its accumulation requires energy to make room for further informative entities, while preserving those which have just been created. We conjecture that the energy-dependent degradation functions in the paleome play this role. We also find among paleome genes some coding for accumulation of a ubiquitous source of energy, which could supply the necessary energy source for rejuvenation of the cell's machinery.
Unlike factories, cells have a built-in process permitting them to accumulate information. This contrasts with the engineering rationale, requiring reproducibility. We provide a conjecture showing how to prevent the process, albeit at the cost of constructing cells which will age and need to be periodically replaced, as we do with present-day factories.