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Mechanism of interaction of antimicrobial peptides with the cell membrane - a study using bio-sensing technologies

Objective

Bacterial resistance to antibiotics threatens global health. Because bacteria have not developed resistance to naturally existing antimicrobial peptides (AMPs), AMPs or their derivatives offer promise as microbicidal agents. AMPs kill microbial cell but rarely damage the mammalian cells that produce and secrete them. Both mechanisms of interaction are poorly understood.

This project will combine novel and standard bio-sensing technologies with alpha-defensins (a-Defs) with varying potencies and distinct mechanisms of membrane disruption in order to test hypotheses directed at the molecular mechanisms of a-Def action. Fully characterised recombinant mammalian a-Defs and a-Defs with site-directed mutations will be used with model membranes that mimic bacterial and mammalian membrane systems. These model membranes, supported on the surface of two biosensors will be used to study the mechanism of interaction of the above AMPs with the membranes.

Optical biosensors based on Surface Plasmon Resonance (SPR) and novel acoustic wave devices based on shear horizontal surface acoustic waves (SH-SAW) will be used to monitor changes in the mass and elasticity of the model supported lipid bilayers during peptide binding. Real time data will be used to derive quantitative information on the binding and kinetic constants of the peptide-membrane. Comparison between optical and acoustic wave data will be used to distinguish between peptide surface binding from bilayer insertion.

We hypothesize that the combination of the above re al time techniques will provide insights into why these endogenous membrane-active molecules do not kill their cells of origin. Proof of these principles is directly applicable to future development of new therapeutic pathways for infectious diseases. In addition the successful application of the above two biosensors will open new possibilities in biophysical analysis and will introduce opto-acoustic measurements as a novel powerful bio-analytical tool.

Call for proposal

FP6-2002-MOBILITY-11
See other projects for this call

Coordinator

FOUNDATION OF RESEARCH AND TECHNOLOGY-HELLAS
EU contribution
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Address
VASSILIKA VOUTON
IRAKLIO, CRETE
Greece

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