Pr. Alain Brisson

Professeur (Pr0), Université Bordeaux 1

Cette adresse email est protégée contre les robots des spammeurs, vous devez activer Javascript pour la voir.

Tel: +33(0)540003458

Bio

Alain Brisson has successively led research groups at the Universities of Strasbourg as Directeur de Recherche at INSERM (87-94) and in Groningen as Professor of Biochemistry (94-01), before moving to the University of Bordeaux as Professor of Biochemistry and group leader at IECB (2001-to date). His main interests are to elucidate the structure-function relationship of complexes between proteins and membranes and to understand the basic principles of their assembly, with a particular interest in annexins. His group develops original molecular tools for applications as biosensors in diagnosis and nanovectors in drug delivery.

Keywords / Expertise / Techniques

proteins, membranes, annexins, phosphatidylserine, calcium, cryo-electron microscopy, AFM, QCM-D, flow cytometry, biosensors, protein production, protein chemistry, nanobiotechnology, surface functionalization, functionalized nanoparticles, diagnosis, drug delivery.

Summary

The team “Molecular Imaging and NanoBioTechnology” develops its research activities along two main orientations: “structure-function studies of annexins and complexes between proteins and membranes” and “nanobiotechnological applications of annexin-based molecular tools”. Basic research projects focus on the relationship between molecular structure, supramolecular organization and mechanisms of 2D assembly of proteins at membrane surfaces, with main interest in effect of annexin-A5 on processes of membrane reorganization associated with phosphatidylserine exposure, principally cell membrane repair and cell fusion processes. Nanobiotehnology-oriented projects focus on the development of molecular tools derived from annexin-A5, for applications in diagnosis and drug delivery.

Activity report

Characterization of Microparticles from Blood Plasma, by Cryo-Electron Microscopyand Annexin-A5 Gold Labeling

Microparticles are membrane fragments that derive from activated or apoptotic cells and are found in plasma and other biological fluids. In plasma, a majority of microparticles originate from platelets. A fraction of plasmatic microparticles exposes at their surface the procoagulant lipid phosphatidylserine (PS) and participates in physiological processes of hemostasis or inflammation. Elevated levels of plasmatic microparticles are found in various pathological disorders, which explains efforts to use microparticles as disease biomarkers. However, the detection and quantification of microparticles is hampered by their small size, which ranges from 50 nm to 1 µm, and the limitations of current analytical methods. Here, we used cryo-Electron Microscopy and PS-specific gold labeling and provided a comprehensive structural description of the whole population of microparticles and the sub-population of PS-exposing microparticles present in plasma or derived from activated platelets. The morphology of plasmatic microparticles is described and size histograms are presented. Platelet-derived microparticles range in size from 50 nm to 3 µm, 75% of them being smaller than 500 nm. PS-exposing microparticles constitute 70% of the total population. This study provides novel structural information on platelet-derived microparticles and opens avenues for characterizing microparticles from different cell origins or associated with various physiopathological situations. (paper in revision at Blood).

Annexin-A5 function

Annexins form a family of soluble proteins that share the property of binding to negatively charged phospholipid membranes in a Ca2+-dependent manner. We have previously shown that several members of the annexin family, the prototype of which is Annexin-A5, self-assemble upon membrane binding into 2D ordered arrays. Basic projects on Annexin-A5 have focused on structure-function relationship studies. The analysis of the elementary interaction between Annexin-A5 and model membranes has been achieved at unprecedented low concentrations, in the fM range. In parallel, we have ultimately discovered the function of Annexin-A5, which participates in a central function in cell’s life (Paper published at Nature Communications).

Development of functionalized nanotools for applications in diagnosis or drug delivery

Nanovectors functionalized with proteins and encapsulating active principles or imaging agents are developed for drug delivery or imaging applications. On-going projects concern vectors of either polymeric or liposomal origin, for the targeting of atheroma plaque, inflammation, breast or colon cancers, and are carried out within collaborations with several Bordeaux teams and at the European level. We have developed various types of Annexin-A5 or Annexin-A5-derived markers, including fluorescent labels, gold particles for Electron Microscopy imaging, and magnetic markers –both magneto-liposomes and polymer vesicles- for MR-imaging. The synthesis of magneto-liposomes has been optimized and protein-functionalized magneto-liposomes have been used for imaging, ex vivo, thrombi sites in atheromatous plaques (Paper in press at Contrast Media and Molecular Imaging).

Scheme of various AnxA5-based molecular tools. (Left): AnxA5-ZZ fusion protein for the controlled immobilization of IgGs or selected antigens; (middle): gold nanoparticle functionalized with oriented AnxA5 or AnxA5-ZZ for the specific labeling of receptors at the (sub)-cellular or tissular level; (right): liposomal nanovector functionalized with AnxA5-ZZ-IgG and encapsulating iron oxide particles for MRI.

 

Selected publications

• Bouter A., Gounou C., Bérat R., Tan S., Gallois B., Granier T., Langlois d’Estaintot B., Pöschl E., Brachvogel B., Brisson A.R. (2011) Annex-in-A5 assembled into two-dimensional arrays promotes cell membrane repair. Nature Communications, DOI 10.1038/ncomms1270.

• Poindron V., Berat R., Knapp A.M., Toti F., Zobairi F., Korganow A.S., Chenard M.P., Gounou C., Pasquali J.L., Brisson A.R., Martin T. (2011) Evidences for Heterogeneity of the Obstetrical Antiphospholipid Syndrome: thrombosis can be Critical for AntiphospholipidInduced Pregnancy Loss. J Thromb Haemost. doi: 10.1111/j.1538-7836.2011.04475.x. 

• Sanson C., Diou O., Thévenot J., Ibarboure E., Soum A., Brûlet A., Miraux S., Thiaudière E., Tan S., Brisson A.R., Dupuis V., Sandre O. and Lecommandoux S. (2011). Doxorubicin Loaded Magnetic Polymersomes: Theranostic Nanocarriers for MR Imaging and Magneto- Chemotherapy. ACS Nano 22:1122-1140.

• Garnier B., Bouter B., Gounou C., Petry K.G. and Brisson A.R. (2009). Annexin A5-functionalized liposomes for targeting phosphatidylserine-exposing membranes. Bioconjugate Chemistry, 20: 2114-2122.

• Soenen S.J.H., Brisson A.R. and De Cuyper M. (2009).Addressing the problem of cationic lipid-mediated toxicity: The magnetoliposome model. Biomaterials, 30, 3691-701.

• Richter R.P., Bérat R. and Brisson A.R. (2006). The formation of solid-supported lipid bilayers – an integrated view. Langmuir 22, 3497-3505.

Research team

• Pr. Alain BRISSON Team leader
• Dr. Anthony BOUTER Associate professor (Mdc, University Bordeaux 1)
• Céline GOUNOU Assistant Engineer (University Bordeaux 1)
• Sisareuth TAN Assistant engineer (CNRS)
• Boris GARNIER Post-doctoral fellow (EU)
• Nicolas ARRAUD PhD student (MENRT)
• Yali WAN PhD student (EU)
• Benoit FAURIE Master student
• Fionna JASSON Master student
• Romain LINARES Master student

The team is part of the unit “Chimie et Biologie des Membranes et Nanoobjets” (CBMN), CNRS/Université Bordeaux 1/IPB (UMR 5248)