*SÉBASTIEN BLAIS-OUELLETTE

Innovative Optical Imaging and Bio-Simulation Platforms to Accelerate Central Nervous System Drug Discovery

Challenge: The development of efficient drugs targeting central nervous system (CNS) diseases remains a challenge, especially because of a lack of effective methods for studying processes occurring at the synaptic level. Protein interactions at the synapse are known to be modified under pathological conditions and to induce important changes in cellular function. Despite great advances in imaging, it remains difficult to define this synaptic plasticity. A better understanding of receptor dynamics and protein-protein interactions is essential for the development of new drug candidates.

Solution: To address this challenge, an innovative multiplexed optical imaging platform has been developed for the simultaneous observation of multiple cellular events, based on Photon etc.’s highly sensitive hyper-spectral detection technology capable of broad wavelength (500–850 nm) coverage for cellular imaging. This imaging platform allows simultaneous detection and tracking of at least 5 synaptic proteins in cultured neurons.
For the first proof-of-concept, the team has been focused on the spatial dynamics of glutamate receptors, a group of receptors implicated in several neurodegenerative conditions, and their interactions with intracellular anchors. These ongoing experiments involve the development of methods to specifically tag multiple receptors with fluorescent probes, in addition to establishing algorithms to analyze their trajectories simultaneously in neurons.

Achievements/Impact: This fluorescence imaging platform is fully functional, and can currently detect up to 5 different labels, but has the potential to simultaneously detect dozens of labels as new adapted labels become available. Using in silico predictions of interactions this innovative platform enables a better understanding of synaptic signaling. This technology will provide unique avenues for the development of new drug candidates targeting CNS disorders. The platform is now in operation at the Neurophotonics Centre. The technology can be extended to other fields where multiplexed analysis is needed.

Principal Investigators:

Sébastien Blais-Ouellette
Photon etc.

Serge Bishoff
Rhenovia Pharma

Co-investigator

Paul de Koninck
Laval University

Completed Project
$1,320,000 / 3 years
Supported by CQDM through:
• AstraZeneca
• Merck
• Pfizer
• MESI
• BL-NCE
And by co-funding partner:
• Alsace BioValley