The
Unit 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.
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