Objective
Systems: This programme of research will address the molecular components Involved in chemical communication as expressed through the olfactory system. Proteins from mammalian and insect sources which bind biologically active small molecules will be structurally and functionally characterised and subjected to techniques in protein engineering to further explore the fundamental structure/function relationships.
Work to date has identified mammalian odour and pheromone-binding proteins with the lipocalin family, but some of this sub-family exhibit unique structural features. Important aspects such as the conformational effects of ligands binding and the consequent influence of the interaction with membrane-bound receptors remain to be elucidated in structural terms. Knowledge of the insect system, which exhibits even greater specificity, is more limited still, the only indication so far being that the carrier proteins do not take up the classical lipocalin fold.
Thus the specific objectives are: (i) the 3D structure of insect PBPs, (ii) the 3D structures of new OBP, PBP-ligand complexes, (iii) conformational dynamic analysis of OBPs and PBPs, (iv) mutagenesis and structure/function analysis of OBPs and PBPs, (v) development-identification of new ligands and ligand-protein complexes, (vi) biotechnological applications of new ligand discovery and protein engineering, (vii) development of new assay procedures, and (viii) analysis of behavioural effects.
Approaches: The principal approaches will be X-ray crystallography and NMR spectroscopy of native and recombinant proteins, with and without ligands. Mutagenesis, protein characterisation and functional assays will be used to investigate the fundamental features of various OBPs and PBPs, which will in turn be correlated with structural properties of interesting constructs, as revealed by X-ray and NMR analysis. Techniques of chemical dissection, synthesis and characterisation will be used for ligand identification and production.
Consortium: A multi-disciplinary team of 8 internationally recognised laboratories in 6 countries will be integrated together to develop a multifaceted analysis of the components of an important but poorly understood biological sensory system. The project falls exactly in the Biotech Structural Biology programme (6.1). The main techniques to be used include (i) determination of new structures (6.1.1) by X-ray crystallography (MARSEILLES, LEEDS) and NMR spectroscopy (MARSEILLES, LEEDS, UTRECHT), (ii) cloning mutagenesis and protein engineering of proteins with desirable properties (6.1.3) (LEEDS, LUND,STUTTGART), (iii) functional analysis with new techniques (6.1.2) (LEEDS, PISA, MARSEILLE), (iv) protein purification and expression (all partners), ligand development identification (PISA, PHEROSYNTHESE), and behavioural analysis (PHEROSYNTHES, VERSAI LLES) .
Applications: Interest from the industrial sector arises principally because of PBPs potential in rodent control (sexual pheromones), in mammalian stress control (porcine appeasing pheromones) and in insect infestation control (insect pheromones).
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsspectroscopyabsorption spectroscopy
- natural sciencesmathematicspure mathematicsmathematical analysisfunctional analysis
- natural sciencesbiological sciencesmolecular biologystructural biology
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Call for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
13402 MARSEILLE
France