Structure, self-assembly properties and mechanism of action of antimicrobial peptides, amyloid peptides and silk proteins

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Our research program focuses on the determination of the structure, self-assembly properties and mechanism of action of several peptides and proteins of biomedical interest. We will focus on antibiotic resistance and neurodegenerative diseases that rely on the structure and assembly of peptides/proteins. We will also study the natural and synthetic production of silk to help in developing biomaterials, especially implants and scaffolds for tissue regeneration. These systems will be investigated by a combination of novel solid-state nuclear magnetic resonance approaches and complementary information will be obtained by several other biophysical techniques.****The dramatic increase in multi-drug-resistant bacteria has led to considerable efforts to find new therapeutic approaches. The design of new antibiotics with novel modes of action is therefore mandatory to fight against microbial infections and antimicrobial peptides are promising candidates. The structure and membrane interactions of synthetic amphipathic peptides will be investigated. More specifically, we will investigate the structure, membrane topology and oligomerization of both lysine-substituted and arginine-substituted peptides.****Comparing the mode of action of natural vs. synthetic antimicrobial peptides is of great interest. We will investigate the interaction of a natural antimicrobial peptide, thanatin, with lipid membranes that model eukaryotic and prokaryotic cells. Since thanatin induces the agglutination of bacteria in vivo, the aggregation of unilamellar lipid vesicles of different compositions will be followed, as well as the secondary structure of the peptide and its membrane interactions.*****Amyloidosis refers to a family of degenerative diseases, including Alzheimer's and Parkinson's diseases, which demonstrate amyloid protein deposits on tissues resulting from the abnormal self-assembly and deposition of proteins into insoluble aggregates known as amyloid fibrils. We propose to investigate the structure and self-assembly properties of two amyloid peptides in solution and associated with membranes, namely a fragment of the protein a-synuclein involved in Parkinson's disease and a fragment of the protein transthyretin involved in different amyloidoses.****Spider silk refers to a range of biological materials made of fibrous proteins that self-assemble in a hierarchical manner to produce various fibers with exceptional mechanical properties and promising applications such as stitches, ligaments and tendons from tissue engineering. We will investigate the structure, thermal stability and aggregation kinetics of recombinant silk proteins in solution. Fibers of flagelliform silk, which forms the capture spiral of orb webs, will also be investigated. We will also determine the structure of the C-terminal domain of silk proteins both in solution and as nanocrystals.***