Dr. Yann Fichou, CBMN/IECB, (Bordeaux) CNRS researcher

I am a research fellow at the CNRS (French National Center for Scientific Research) at the Institute of Chemistry and Biology of Membranes and Nanoobjects in Bordeaux. I work on the amyloid aggregation of a protein called tau. These aggregates accumulate in neurons during Alzheimer's disease. Understanding how these aggregates form and propagate in the brain is essential for understanding the genesis and development of the disease. This is the goal of this project.

Tau is an intrinsically disordered protein (IDP), meaning that it does not have a well-defined 3D structure but rather behaves like a polymer. Yet, it fulfills a well-defined function in vivo, which is to regulate microtubule activity in neurons. Under pathological conditions, tau forms highly ordered amyloid aggregates that are involved in various diseases, called tauopathies, including Alzheimer's disease. In this project, we aim to provide a real-time molecular description of the disorder-to-order transition between the soluble and aggregated forms of tau. To achieve this, electron paramagnetic resonance (EPR) offers a unique opportunity to monitor the structural and dynamic changes of tau during this transition. In particular, we are using DEER at BIP Marseille to monitor the structural rearrangements of tau under various pathogenic conditions that lead to the formation of amyloid aggregates.

DEER-type experiments allow the monitoring of tau protein conformations in solution and during pathogen interactions.

Platform used: Pulsed X-band EPR, BIP laboratory, Marseille