Biomedical subjects
Publications and source records attributed to A Danchin.
The information collected in national and international libraries on nucleotide and protein sequences cannot be directly treated for proper handling by existing software. Therefore we evaluated the feasibility of constructing a data base for Escherichia coli using the data present in the banks. The knowhow thus acquired was applied to Bacillus subtilis. Specific examples of the general procedure are given.
The phosphoenolpyruvate phosphotransferase system (PTS) component EIIIGlc is responsible for transport and phosphorylation of glucose via EIIGlc. It also regulates the catabolism of other carbon sources, such as lactose and maltose, by modulating both the intracellular concentrations of the corresponding inducers and of cAMP. Mutational analysis of EIIIGlc was performed in order to identify crucial residues mediating the interactions between EIIIGlc and its target proteins. Such mutations were isolated by in vitro hydroxylamine mutagenesis of the cloned EIIIGlc gene, crr. Five mutated EIIIGlc impaired in the function of inducer exclusion were obtained. However, these mutations did not abolish the function of EIIIGlc in the transport and phosphorylation of glucose, nor in activation of adenylate cyclase. A single amino acid change was found for each mutation, which is located in a restricted area of the polypeptide chain: Gly47-->Ser47 for the HA2 and HA5 mutations, Ala76-->Thr76 for HA4 mutation and Ser78-->Phe78 for HA3 mutation, indicative of quaternary interactions between the corresponding region of EIIIGlc and its target protein(s).
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Most recently published complete bacterial genomes have revealed unexpectedly high numbers of long strict repeats. In this article we discuss the various functional and evolutionary roles of these repeats, focusing in particular on their role in terms of genome stability, gene transfer, and antigenic variation.
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An immunoenzymatic procedure has been developed based on the use of monoclonal antibodies specific for 5-bromodeoxyuridine (BdUr). It allows the detection of BdUr-labelled DNA immobilized on a nitrocellulose filter. Using this procedure, it was possible to detect up to 0.5 pg of mammalian DNA labelled in vivo with BdUr, 5 pg of nick-translated BdUr-labelled PBR-322 and, using this latter probe and dot-blot hybridization, 50 pg of native unlabelled PBR-322.
A new selective theory for the specification of the antibody production is presented. It is grounded on the following postulates: (a) the antigen stimulus triggers the synthesis of antibodies having a wide variety of specificities in a given immunocompetent cell and its progeny; (b) only these antibodies having affinity for the antigen have their synthesis stabilized, and competition between the diverse syntheses will favor the antibodies having the highest affinity; (c) there existes a threshold synthesis such that when the production of an antibody becomes lower than the threshold, it will go to zero. As a consequence, one should observe, immediately after the antigen stimulus, the transient appearance of a large number of seemingly unspecific immunoglobulins, followed by specific antibodies. The apparent binding constant of these antibodies should also increase during the specification period. Besides, one should observe a small, but detectable amount of self antibodies during the early period of specification. Finally, in the presence of several antigens, one should find cells which appear to produce antibodies against several antigens during a transient period.