Objetivo
The microorganism H. pylori plays a significant role in the development of gastritis and peptic ulcers and has also been implicated as a causative agent of gastric adenocarcinoma and B-cell lymphoma of the stomach. The cell surface lipopolysaccharides of certain H. pylori strains carries immunodeterminant groups that are similar to structures present in the host and may camouflage H. pylori upon initial infection in the gastric mucosa. These structures mimic Lewis x and y blood group antigens and appear to elicit an autoimmune response upon chronic infection. The mimicry is probably related also to recurrence of infection.
The objective of the proposal is to study the mechanism by which different Helicobacter pylori, strains causes different diseases such as gastritis and peptic ulcers. The goal is to pinpoint structural features that cause different states of disease.
For these purposes, pertinent H. pylori strains will be selected by serology and lectin typing, propagated, the lipopolysaccharides will be isolated, their complete structures will be established using chemical methods as well as mass spectrometry and NMR spectroscopy, their conformations will be calculated using molecular modelling to evaluate parts which are accessible for recognition. In addition the lipopolysaccharides will be tested in appropriate biological systems, using serological reactions with rabbit anti-H. pylori polyclonal antibodies, monoclonal anti-Lewis antibodies, and antibodies specific to the conservative core region of the lipopolysaccharide
The expected results will allow us to answer the question: Which H. pylori strains are likely to give recurrent and severe infections? The structural data will serve also as the chemical basis for a reliable classification scheme of H. pylori strains which is necessary for research and epidemiological purposes. Structural information will be used for the formulation of a carbohydrate-based LPS-derived vaccine component and for characterisation of monoclonal antibodies which can be a useful tool for serodiagnostics of H. pylori infection.
The groups that are participants in this project all have previous joint projects or other close contact with each other and good records of scientific collaboration. Furthermore, the input from three chemistry/spectroscopy/modelling groups and two groups with solid background in biology/immunology is a guarantee that significant progress should be made within the project.
Tema(s)
Convocatoria de propuestas
Data not availableRégimen de financiación
Data not availableCoordinador
141 86 Huddinge
Suecia