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Optical imaging and biosimulation platforms to speed CNS drug
Québec: Sébastien Blais-Ouellette (Photon Etc.) and Paul De Koninck (Université Laval et Centre de Neurophotonique)
Alsace: Serge Bischoff (Rhenovia Pharma)
$700,000 over 3 years (for the research being performed in Québec)
Fundamental mechanisms underlying diseases of the central nervous system (CNS), such as Alzheimer’s, Parkinson’s, Huntington’s, schizophrenia, depression or autism remain poorly understood, partly due to a lack of appropriate methods for investigating the complex CNS molecular processes. The critical sites in the brain that are particularly challenging to reach are the billions of tiny sites of neuronal connections: the micron scale synapses. This limitation explains in part the relative poor efficacy of existing treatments and the failure to discover innovative treatments for CNS diseases in the past decade.
This proposal is aimed at developing new tools to allow a better understanding of neurotransmitter receptor dynamics and protein-protein interactions at the synapse, in response to drug candidates. Two highly innovative and complementary platforms will be developed: 1) a multiplexed optical imaging platform for the observation of multiple cellular events simultaneously, based on Photon etc. highly sensitive hyperspectral detection technology, capable of broad wavelengths (400-2500 nm) coverage for cellular imaging, and 2) an in silico biosimulation platform to model and predict drug effects at different levels of neuronal signaling, based on Rhenovia’s powerful and unique program capable of taking into account multiple levels of analyses of brain functions. The experimental validation will be performed on cell lines and neuronal cultures, under the exposure to various drugs.
The combination of these platforms will provide unique guidelines for the development of new drug candidates targeting CNS disorders. Impact on the drug discovery process - Better modeling of drug effects using the in silico biosimulation platform to assess and predict dynamic protein-protein interactions - Improvement of CNS drug discovery by reducing the timelines, increasing the depth of data and supporting early go/no go decision making of drug candidates - Increase the predictive value of cellular imaging using the multiplexed labels allowing detection of 5 to 10 distinct signals simultaneously - Increase fundamental knowledge on CNS mechanisms of learning, memory, cognition and neural plasticity
The Enlightened Brain
February 25th 2011
Researchers from the Robert-Giffard research centre have developed a combined optical and electrical probe that unveils new horizons in brain neurophysiology.
By Jean Hamann (Translated from the original text by Mario Méthot)
A team of researchers in neurosciences and optics-photonics have just developed a new kind of electrode that renders possible the study of individual neurons in the in vivo brain. The details concerning the functioning of this unique tool have been published on the 13th of February, 2011 on the web site of Nature Methods by Yoan LeChasseur, Suzie Dufour, Guillaume Lavertu, Cyril Bories, Martin Deschênes, Réal Vallée, and Yves De Koninck. ‘This is a new electrode, being at the same time electrical and optical’, explains professor De Koninck. This ‘optrode’ allows researchers to better exploit the advantages of biophotonics in brain neurophysiological studies. One can also imagine some applications in neurosurgery and optogenetics in humans.
Link to the scientific article on Nature Methods:
http://www.nature.com/nmeth/journal/v8/n4/abs/nmeth.1572.html
To get the PDF version of the article, click here
DPMB prize awarded to Suzie Dufour during the 2010 ACP congress for the best oral presentation by a student (third prize).
Title : Spatial resolution of optical fibre micro-probe and their use in vivo.
Abstract: Optical micro-probes made from tapered optical fibres can be used in vivo as fluorescent sensors to detect labelled cells or to measure their activity using functional dyes such as calcium indicators. In the configuration we proposed [1, 2], the same tapered fibre is used to carry the excitation light into the tissue and to collect the fluorescence originating from the sample.
To better analyse the results obtained with these probes, we calculated and measured their spatial resolution (detection volume). Knowing the detection volume of the probe is important to evaluate the probability of recording from one cell or the capacity to resolve adjacent cells. A numerical simulation (performed with Matlab) was used to evaluate the impact of the excitation profile (gaussian or homogeneous), the probe numerical aperture, the index profile of the fibre, the probe diameter, and the excitation and collection wavelength on the spatial resolution. The spatial resolution was also measured using small fluorescent micro- spheres (2 μm) for different probe diameters. A 488 nm solid state laser was used for excitation. The micro-spheres were moved in front of the probe tip in a controlled fashion, and the collected fluorescence was measured for each position of the micro-sphere, which allowed us to obtain the axial and traversal resolution. When comparing the estimated and measured resolutions for a given probe we found that they were comparable. Finally, we present examples of fluorescent cell detection, in fixed tissue and in living animals.
Funded by CIHR and NSERC. S.D. and Y.L. are supported by Studentships from the CIHR Neurophysics Training Program.
2010 CIPI Young Photonics Innovator Award (prix du jeune innovateur en photonique de l'ICIP 2010) à Stéphane Pagès et Sophie Laffray
Description of the innovation: We developed a non invasive strategy to adapt high resolution functional optical imaging to moving CNS structures with subcellular spatial resolution at millisecond time scales in living animals. The Image Plane Locking system (IPL) is a fast adaptive non-contacting device to compensate for movement (up to 100 mm) within very short time (< 10 ms). The device operation is based on a continuous optical monitoring of the position of the tissue and a feedback system to control the position of the objective. This maintains constant the distance between the tissue and the objective. The IPL allows for compensation of rapid movements (e.g. breathing and pulsations) and locking of the plane of interest in focus. This new in vivo functional imaging approach allows millisecond resolution in moving tissue with minimal invasiveness, and provides a powerful tool to study network activity.
Funded by CIHR and NSERC. S.P. and S.L. are supported by Studentships from the CIHR Neurophysics Training Program.
A new graduate program (M.Sc. and Ph.D. levels) in Biophotonics just opened at Université Laval. The Neurophysics group was significantly involved in the creation of this program which will start in Fall 2008. Paul De Koninck is the director of the program in Biophotonics while Mario Méthot will take charge of the coordination aspect. More information about the graduate program in Biophotonics.