The seminar will take place, the 26th of May,at 16h, at the ENSCBP amphitheater, Building B, allée Geoffroy Saint-Hilaire, Pessac.
UMR8576 CNRS-Lille University, F-59000 Lille, France.
Tau pathologies, called ‘tauopathies’, are related to several neurodegenerative diseases including Alzheimer Disease (AD). In AD, Tau protein is observed hyper-phosphorylated and aggregated as Paired Helical Filament (PHF). The molecular mechanisms of Tau-linked neurodegeneration is far however from being elucidated. Tau is a paradigm for the growing class of “intrinsically disordered proteins”, often found associated with pathologies such as neurodegenerative diseases, hence increasing the interest to grasp the molecular parameters underlying their functions.
The fine structural characterization at the molecular level of Tau and its interactions remain challenging due to its highly dynamical character. Additionally, 80 Ser/Thr residues in the longest Tau isoform, potential sites of phosphorylation, can be combined to give a multiphosphorylated Tau, leading to a very complex regulation of Tau interactions. Nuclear Magnetic Resonance (NMR) Spectroscopy is used to define the phosphorylation pattern of Tau samples, to investigate the impact of specific patterns of phosphorylation on structural determinants of Tau and to characterize Tau interactions with its molecular partners and their regulations.
Comprehension of the dynamic combination of these aspects represents a huge task but will probably be the key to therapeutic intervention on Tau pathway.
Selected Publications related to the seminar
Qi H, et al., Landrieu I. Characterization of Neuronal Tau Protein as a Target of Extracellular Signal-regulated Kinase J. Biol Chem. 2016/A Phosphorylation-Induced Turn Defines the Alzheimer's Disease AT8 Antibody Epitope on the Tau Protein.Angew Chem Int Ed Engl. 2015/ Milroy LG, et al., Landrieu I, Ottmann C. Stabilizer-Guided Inhibition of Protein-Protein Interactions. Angew Chem Int Ed Engl. 2015/ Qi H, et al., Landrieu I. Nuclear Magnetic Resonance Spectroscopy characterization of Tau interaction with DNA and its regulation by phosphorylation. Biochemistry. 2015/Sibille N, et al., Landrieu I. Structural characterization by nuclear magnetic resonance of the impact of phosphorylation in the proline-rich region of the disordered Tau protein. Proteins 2011
1993 Engineering degree (Applied Chemistry and Biotechnology) University of Liège, Gembloux, Belgium.
1997 PhD thesis in Agronomy and Biological engineering University of Liège, Gembloux, Belgium.
2003 Habilitation à Diriger des Recherches, Lille University, France
PhD student at EMBL outstation in Grenoble (1994-1997)
Postdoctoral fellow at Plant System Biology Lab, Ghent, Belgium, Advisors D. Inzé and M. Von Montagu (1997-2001)
Scientist at CNRS since 2001, Present position: DR2, CNRS.
Contact: Christophe Cullin (firstname.lastname@example.org)