Summary of scientific activities of UPMTG  
 
founded by Maurice Hofnung

acting director : Jean-Marie Clément

 


      The U
nit of Molecular Programming and Genetic Toxicology (UMPGT) is interested in the organisation, the stability, the evolution and the expression of the genome of gamma proteobacteria. Studies are developing along four main research axes.  
       The two first lines of research derive from the study of  a complex genetic locus of the model bacterium
Escherichia coli K12 (the malB region) and of the corresponding proteins, as well as of highly repetitive sequences initially discovered within this region. The malB region encodes five proteins located in the bacterial envelope. They  cooperate to concentrate into the cell a family of sugars, maltose and maltodextrins. Three of these proteins are associated with the inner membrane, where they constitute one of the first discovered ABC transporters (for ATP Binding Cassette) and one of the best understood in molecular terms. These transporters are widespread throughout the living world (over 1500 are presently known) and have extraordinarily varied substrate specificities. Several play important functions in humans and their defects lead to severe genetic diseases. Our recent work contribute to define more precisely, down to the atomic level, the interactions between these three proteins during transport. An ongoing study of the phylogeny of these proteins lead us to propose that: i) these proteins have evolved in a concerted way and ii) segregation between import systems such as the maltose transport system and export systems such as protease secretion by Erwinia chysantemi (studied in another Unit of this Department) occurred very early in evolution, perhaps in the primordial cell. We also investigate the two other proteins of the maltose transport system: one, the maltose binding protein is located in the periplasm; the other one, the maltoporin, is within the outer-membrane where it also plays the role of bacterial receptor for phage Lambda. Finally, the malB region first revealed the existence of highly repetitive palindromic DNA sequences, dispersed on the bacterial chromosome ( BIME for Bacterial Interspersed Mosaic Element). We examine the hypothesis that they could play a role in the functional organisation of the bacterial chromosome. We discovered and study an insertion sequence (IS1397) which inserts into BIMEs with a strict specificity.
       The third line of research is part of a preventive approach which consists of detecting products from the environment able to modify the genome-
genotoxic agents -and thus likely to be mutagenic and/or carcinogenic in man. After having developed a simple bacterial test, the "SOS Chromotest", to rapidly examine the genotoxic ability of chemicals and radiations , the  focus is on the mechanisms of action of an extremely potent mutagen, R7000 belonging to a chemical family, the nitrofurans, which are used in the pharmaceutical and food processing industries. The genotoxic effects are studied on bacteria, but also on transgenic mice.  
       The fourth research axis was brought into the Unit by a new group dealing with bacterial
super-integrons . These may include more than 150 consecutive genes under the form of cassettes on the bacterial chromosome. The cassettes are tagged so that they can insert into, and excise from, the super-integron thanks to a specifi recombinase. The present inventory suggests that these cassettes often encodes functions involved in the interaction between the bacteria and their environment (resistance to antibiotics, pathogenicity, response to stress, etc..). We try to evaluate the pool of genes susceptible to insert into super-integrons, the distribution of super-integrons  among bacterial species, the mechanisms for increase the size of the gene pool as well as the mechanisms for specific recombination. The internet page of the Unit displays a Genetic Toxicology data base , a data base on repetitive sequences in bacteria , and a data base on ABC transporters. These bases are kept up to date and will become progressively more and more user friendly.
 

Webmaster :              Philippe Bouige             pbouige@pasteur.fr        tel : 01 45 68 88 3
secretariat : Ana Cova-Rodrigues  
acova@pasteur.fr tel : 01 45 68 88 30