Structural Biology of Bacterial Macromolecular Complexes (SBBMC)

Equipe de recherche
RESPONSABLE
Laurent Terradot
laurent.terradot@ibcp.fr
0633 697 314  

CHAMPS D’EXPERTISE

X-ray crystallography, Helicobacter pylori, stomach cancer

ACTIVITES DE RECHERCHE / SERVICES

Helicobacter pylori is is a Gram-negative bacteria that infect the gastric mucosa of about half of the world population and may cause chronic gastritis, peptic ulcer disease or gastric cancer. Although for most individuals the infection is asymptomatic, H. pylori will provoke gastric or duodenal ulceration in about 20 % of infected individuals and in 1-2% even gastric cancer.  With around 750 000 cases of death/year, H. pylori-mediated gastric cancers are the third leading cause of cancer in the world. Although antibiotics are currently used to treat the infection, a rapid increase of antibiotic resistance causes more and more problems for a successful treatment as stated by the WHO.

 The most virulent strains of H. pylori, i.e. more frequently associated with cancer, carry a highly sophisticated protein injection system, the cag Type 4 secretion system (T4SS). Using this type of molecular syringe, H. pylori delivers the bacterial protein toxin CagA into different types of host cells. The “needle” of the syringe is termed the pilus and is known to attach to the host cell. Once injected, CagA interferes with host cell signalling cascades, resulting in a reprogramming of these cells, eventually leading to their malignant degeneration. The structure of the cagT4SS and of its pilus, its assembly and how it injects CagA is still very poorly understood. Our team has focused its research program on 1) the determination of the cagT4SS structure and mechanism of CagA injection and 2) development of targeted inhibitors against H. pylori infection. Thus our group’s activity fits very well with the CLARAAxis 2 : Infections, Immunity and Cancer 

Our group studies key processes of Helicobacter pylorinfection at the molecular and structural level. We employ a large and complementary set of biochemical, structural and biophysical methods including: molecular biology, protein expression and purification, protein-protein interactions (Multi-angle laser light scattering, isothermal titration calorimetry, SPR) and structural biology (X-ray crystallography, electron microscopy and SAXS).  Our expertise lies in the study of the assembly of large, dynamics macromolecular complexes.

COMPETENCES / MOYENS TECHNIQUES

X-ray crystallography, protein-protein interaction studies, cryo-electron microscopy.

OU NOUS TROUVER ?

UMR5086 Molecular Microbiology and Structural Biochemistry (MMSB)
IBCP, 7 passage du Vercors
69367 cedex 7 LYON
http://perso.ibcp.fr/laurent.terradot/terradot_lab/Terradot_Lab.html