25–30 May 2020, Spetses Island, Greece
Our main focus is to investigate the molecular aspects responsible for the interaction between microtubules and intermediate filaments, and evaluate the consequences of altering these interactions. In particular, we identified the sites on which tubulin is binding to intermediate filaments, also known as Tubulin-Binding Sites (or TBS). For example, the NFL-TBS.40-63 peptide (for NeuroFilament Low subunit-Tubulin Binding Site 40-63), also known as NFL-peptide, has been shown to specifically penetrate glioblastoma in all cell lines tested (rat, mouse and human), in which it binds to ß-III-Tubulin, and block its polymerization into microtubules, without affecting the microtubules of other cells of the nervous system. Thus the peptide inhibits the in vitro cell division of glioblastoma cells and their tumor development in vivo on rats Bocquet et al. 2009, Berges et al. 2011). Similarly, we showed that the NFL-peptide is able to enter in glioblastoma stem cells isolated from patients, where it induces their death by apoptosis (Lépinoux-Chambaud & Eyer, Accepted), as well as in glioblastoma cells from dogs. The peptide is also able to target neural stem cells, but without effects on microtubules (Lépinoux-Chambaud & Eyer 2013). When nanocapsules are functionalised with the peptide, it is possible to target their entry in these cells both in-vitro and in-vivo (Balzeau et al. 2013, Laine et al. 2013, Caradorri et al. 2016, 2018, Karim et al. 2018). Finally, when investigated at the ultrastructural level, a new organisation of the peptide into new nano-structures has been observed. The presentation will document both these biological properties of the NFL-peptide to enter selectively in different type of cells of the nervous system, the cytotoxicity of the NFL-peptide and its impact on tubulin.
We use a panel of complementary techniques, including biochemistry, cell biology, nanotechnologies, and transgenic mice. We are focusing mostly on the nervous system: neurons, oligodendrocytes, astrocytes, and also glioblastoma.
Our laboratory is offering several ways to test the effects of products the normal and pathological nervous system.
We are also developing nanocapsules as well as guided nano-robots.
We have fluorescent microscopes, confocal microscopes, transmission and scanning electron microscopes. Our animal facility can perform surgical procedures, in particular stereotaxic injections.
We are looking for collaborations in order to target the entry of nanocapsules into specific cells and/or to affect the cytoskeleton in these specific cells.
We are also interesting to evaluate the peptides corresponding to the Tubulin-Binding Sites isolated from different intermediate filaments (keratin, vimentin, neurofilaments, GFAP…) on cell biology and development.
Barreau K., Montero-Menei C.N., Eyer J. (2018) The neurofilament derived-peptide NFL-TBS.40-63 enters in-vitro in human neural stem cells and increases their differentiation. PlosOne doi: 10.1371/journal.pone.0201578. eCollection 2018.
Carradori D., Saulnier P., Préat V., des Rieux A., Eyer J. (2016) NFL-lipid nanocapsules for targeting brain neural stem cell in vitro and in vivo. J Control Release. 238, 253-262.
Lépinoux-Chambaud C., Barreau K., Eyer J. (2016) The neurofilament-derived peptide NFL-TBS.40-63 targets neural stem cells and affects their properties. Stem Cells and Translational Research. 7, 901-913.
Balzeau J., Pinier M., Berges R., Saulnier P., Benoit J-P. and J. Eyer. (2013) The NFL-TBS.40-63 peptide improves the in vitro and in vivo targeted uptake of lipid nanocapsules by glioblastoma cells. Biomaterials 34, 3381-3389.
Berges R., Balzeau J. Peterson A. Eyer J. (2012) A tubulin binding peptide targets glioma cells, disrupts their microtubules, blocks migration and induces apoptosis. Mol. Ther. 20, 1367-1377.
25–30 May 2020, Spetses Island, Greece