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Responsable de l’équipe de recherche

Peter FALLER

Année de création de l'équipe - 2015

Secrétariat et gestion assurés par

Paola SAGER
courriel : sager@unistra.fr
téléphone : 03 68 85 13 06

Personnels permanents

Personnels non permanents

Post-doctorante :

Paulina GONZALEZ  -  Courriel : paulina.gonzalez@unistra.fr

Doctorante :

Alice SANTORO - Courriel : alice.santoro@unistra.fr

Descriptif de l'équipe de recherche

Our research group works at the interface of chemistry with biology. The main topic deals with amyloidogenic peptides and their interaction with d-block metal ions like copper and zinc. Amyloidogenic peptides can form amyloids by a self-assembly process. Amyloids are fibrils of about 10 nm diameter and several 100ds of nm length and they are found in several diseases, in particular in neurodegenerative diseases (Alzheimer, Parkinson, Prion,…). Our main focus is on the peptide amyloid-beta, which aggregation seems to be directly related to and may be causative for Alzheimer disease. High amounts of copper, zinc and iron irons are found bound to amyloid-beta in the amyloid plaques in Alzheimer patients. Therefore we are interested in how these metal ions interact with amyloidogenic peptides, e.g. to decipher how they impact the self-assembly process and what is the reactivity of these complexes between metal and amyloidogenic peptides. Latter could explain their harmful effects on cell. In thjis context we are particularly interested in the mechanism of production of reactive oxygen species by Cu-amyloid-beta. We study also the interaction with other metalloproteins concerning metal-exchange reactions or with small compounds like fluorophores (for detection) or inhibitors (potential therapeutic agents).

Main Methods:

- Spectroscopical methods (EPR, NMR, X-ray absorption spectroscopy, circular diochroism, absorbance, fluorescence …)

- Other physico-chemical methods: microscopies (AFM, TEM), isothermal titration calorimetry)

- Biochemical methods (chromatography, electrophoreses)

- Peptide Chemistry

Key words:

biometals; bioinorganic chemistry; bioorganic chemistry; copper, zinc, iron; peptides; Chemical protein synthesis; bioconjugation; metalloproteins, reactive oxygen species, self-assembly; amyloids; metal trafficking; fluorophores; inhibitors; spectroscopies.

Thèmes de recherche

- Structure of metal-peptide/protein complexes (amyloid-beta, serum albumin, synuclein, etc.)

- Metal transfer between amyloidogenic peptides and proteins (like serum albumin, metallothionein)

- Self-assembly of amyloidogenic peptides into amyloid fibrils:  effect of metal ions chaperons, inhibitors, etc.

 - Fluorescent molecules and techniques to monitor the self-assembly process and/or metal-binding

- Chemical reactivity of metal-peptide/protein complexes; metal centered catalysis

- Protein total synthesis

Références bibliographiques récentes

REVIEWS:

Amyloid β Protein and Alzheimer's Disease: When Computer Simulations Complement Experimental Studies. Nasica-Labouze J, Nguyen PH, Sterpone F, Berthoumieu O, Buchete NV, Coté S, De Simone A, Doig AJ, Faller P, Garcia A, Laio A, Li MS, Melchionna S, Mousseau N, Mu Y, Paravastu A, Pasquali S, Rosenman DJ, Strodel B, Tarus B, Viles JH, Zhang T, Wang C, Derreumaux P. Chem Rev. 2015, 115, 3518-63.

Metal ions and intrinsically disordered proteins and peptides: from Cu/Zn amyloid-β to general principles. Faller P, Hureau C, La Penna G. Acc Chem Res. 2014, 47,2252-9.

Role of metal ions in the self-assembly of the Alzheimer's amyloid-β peptide. Faller P, Hureau C, Berthoumieu O. Inorg Chem. 2013,52, 12193-206.

ORIGINAL ARTICLES:

Free Superoxide is an Intermediate in the Production of H2 O2 by Copper(I)-Aβ Peptide and O2.
Reybier K, Ayala S, Alies B, Rodrigues JV, Bustos Rodriguez S, La Penna G, Collin F, Gomes CM, Hureau C, Faller P.
Angew Chem Int Ed Engl. 2016, 55, 1085-9.

Combined Experimental and Simulation Studies Suggest a Revised Mode of Action of the Anti-Alzheimer Disease Drug NQ-Trp. Berthoumieu O, Nguyen PH, Castillo-Frias MP, Ferre S, Tarus B, Nasica-Labouze J, Noël S, Saurel O, Rampon C, Doig AJ, Derreumaux P, Faller P. Chemistry. 2015 , 21, 12657-66

Concept for simultaneous and specific in situ monitoring of amyloid oligomers and fibrils via Förster resonance energy transfer. Alies B, Eury H, Essassi el M, Pratviel G, Hureau C, Faller P. Anal Chem. 2014, 86, 11877-82

The catalytically active copper-amyloid-Beta state: coordination site responsible for reactive oxygen species production. Cassagnes LE, Hervé V, Nepveu F, Hureau C, Faller P, Collin F. Angew Chem Int Ed Engl. 2013, 52, 11110-3.

Liste du matériel et des appareils

- Plate reader to measure fluorescence and absorbance in 96 or 384 wells plate

Galerie photos de l'équipe de recherche

Un petit aperçu de notre équipe de recherche