PROJECT: JTC2012: MICRODEG

The present project aims at combining microfluidic technology with microelectrode arrays and recent progress in neuronal stem cells, in order to develop new in vitro models allowing the reconstruction and electrical control of fully functional mouse and human neuronal networks. These reconstructed networks will be used to model neurodegenerative syndromes and to investigate "prion-like" propagation phenomena at the neuronal network and cellular. More specifically, by creating artificial networks derived from neuronal cells derived from transgenic mice over expressing mutant forms of aggregation prone proteins (synuclein and huntingtin), or from human iPSC's derived from disease patient, challenged or not by a diversity of misfolded proteins obtained from affected brains or in vitro generated; we propose to study the spreading of neurodegenerative hallmarks along reconstructed brain pathways. The project will involves 5 complementary research teams specialized in basic and applied molecular Neurosciences and specialists of microfluidic technologies and neuro-electronic interfacing. More generally, such a system would be highly needed both on a fundamental level, to facilitate the unraveling of the different bio-molecular processes at play in different neurodegenerative events and of their causality chains (and thus to discover new target and potential mechanism of action for future drugs), and downstream in the drug development streamline, to efficiently screen in vitro and validate potential drug candidates.