Objective
IMPROVED UNDERSTANDING OF THE MOLECULAR BASIS OF ANTIGEN-ANTIBODY INTERACTIONS LEADING TO BASIC INFORMATION ON SIGNAL GENERATION BY ANTIBODY BINDING AND SIGNAL TRANSDUCTION.
IMPROVED ELECTRONIC AREA DETECTOR AND SOFTWARE FOR SPEEDIER X-RAYS ANALYSIS OF PROTEINS.
LONG TERM ECONOMIC BENEFITS IN HEALTH CARE INDUSTRIAL BIOTECHNOLOGY E.G. SYNTHETIC ENZYMES.
Research was carried out to determine, by X-ray crystallography, the 3-dimensional structures of:
antigen antibody complexes for which hen eggwhite lysozyme (HEL) was used as the model antigen;
heterologous antigens (other avian lysozymes);
FabNQ10 (from a monoclonal antiphenyloxazolone antibody) and its complexes with specific haptens;
an idiotope antiidiotope complex.
Results obtained in the study of the 3-dimensional structures were:
the determination of those of FabNQ10 free and bound to the phenyloxazolone hapten;
the refinement of the atomic coordinates of the antigen antibody complex FabD1.3-HEL;
the determination and refinement of the structures of the heterologous antigens, turkey and Japanese quail lysozymes;
the determination of the structure of an idiotope antiidiotope complex.
Another major result obtained was that of reshaping human antibodies: the antilysozyme activity of the mouse monoclonal antibody D1.3 was grafted by recombinant deoxyribonucleic acid (DNA) techniques onto a human immunoglobulin, a technique which should facilitate the production of therapeutic human (chimaeric) antibodies. The variable domains of the heavy chains (VH) and light chains (VL) of D1.3 were cloned and expressed in Esherichia coli. It was found that the VH domain binds lysozyme with an affinity constant (Kd = 19 nM) which is only 1 order of magnitude lower than that of the parent antibody (Kd = 2 nM).
THIS IS A JOINT PROJECT TO STUDY THE MOLECULAR BASIS OF ANTIGEN-ANTIBODY INTERACTIONS.
THE SPECIFIC AIMS OF THE RESEARCH WORK TO BE CARRIED OUT AT LURE ARE :
1) TO PURSUE AND CONSOLIDATE THE DEVELOPMENT OF AN ELECTRONIC AREA DETECTOR (BASED ON A SPHERICAL-DRIFT MULTIWIRE CHAMBER BUILT AT CERN) AS AN INSTRUMENT FOR HIGH-SPEED AND HIGH-ACCURACY DATA COLLECTION. MORE SPECIALLY, TO SUPPLEMENT THE PRESENT HARDWARE BY PROFESSIONALLY-WRITTEN SOFTWARE FOR THE ON-LINE TREATMENT OF THE RAW DATA ON AN ARRAY PROCESSOR.
2) TO CONTINUE THE DEVELOPMENT OF PHASING METHODS AIMED AT PRODUCING GOOD QUALITY ELECTRON-DENSITY MAPS.
3) TO DEVELOP SPECIFIC COMPUTATIONAL METHODS FOR EXPLOITING AS AUTOMATICALLY AS POSSIBLE THE KNOWN STRUCTURAL CHARACTERISTICS OF F FRAGMENTS ON THE PHASE DETERMINATION PROCESS, SO AS TO SPEED UP THE X-RAY ANALYSIS OF CRYSTALS CONTAINING THESE MOLECULES.
SPECIFIC AIM 1) WILL BE THE MAIN FOCUS OF THE EXTRA EFFORT FOR WHICH EEC SUPPORT IS BEING SOUGHT BY THE PRESENT CONTRACT.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences physical sciences theoretical physics particle physics
- natural sciences biological sciences genetics DNA
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences computer and information sciences computational science
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Coordinator
91405 Orsay
France
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