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Neurophotonics.Ca

at the interface of physics & neuroscience

COVF Testing nodes

Human cells & tissue

Non-Human Primates

Rodents

Invertebrates & Lower Vertebrates

Invertebrates & lower vertebrates

This node includes

  • the Zebrafish testing site at the CERVO Brain Research Center (Université Laval), and
  • the Tadpole testing site at The Neuro (McGill), and
  • the Invertebrate (Drosophila) testing site (McGill).
Read more about the invertebrates & lower vertebrates testing sites

The Zebrafish testing site includes experts in genetic engineering and live optimal imaging (confocal, multi-photon, video-wide field) in zebrafish. The team is specialized in structural and functional multi-plane whole zebrafish brain imaging with single neuron resolution, as well as synaptic imaging in individual neurons in zebrafish brain. Eggs are injected with the gene(s) of interest upon fertilization with plasmids encoding various sensors, such as those developed by our colleagues from the Protein Engineering Core. Tests are conducted to verify their expression, functionality, and properties; providing a rapid and critical feedback on the suitability of the newly developed tools for in vivo applications in this model.

The Tadpole (Xenopus) testing site has been studying Xenopus neurodevelopment for two decades.  The testing model starts with any plasmid that bears the sequence of a novel fluorescent protein (FP) or reporter.  The gene is subcloned into an mRNA expression vector, mRNA synthesized in vitro, and microinjected into in vitro fertilized Xenopus embryos at the one- or two-cell stage of development.  This typically results in rapid whole-animal expression of the gene of interest.  Using in vivo 2-photon microscopy, the function of the gene product can be assessed in any organ of the rapidly developing embryo – typically the central nervous system – and its activity quantitatively compared to other benchmark FPs such as GCaMP6s.  The entire pipeline from DNA sequence to in vivo CNS characterization takes approximately two weeks.

The Invertebrate Testing Site is largely based on the fruitfly (Drosophila) model. Drosophila larvae have a rich repertoire of behaviors, responding to specific stimuli and using various strategies to escape from negative stimuli.  Escape behaviors are critical for survival and require optimal performance.  To achieve such performance, the larval brain must produce specific spatiotemporal patterns of output appropriate to the corresponding patterns of input.  Such decisions require multisensory integration—a process that is difficult to study in a large nervous system because the convergence of neural signals must be tracked at many sites. The neuron-behavior relationships analysis combines 1) genetic tools to manipulate individual neurons; 2) a high-throughput behavioral tracking system that allows temporally controlled stimulation of many freely moving larvae at once; 3) TEM neuron reconstruction; and 4) unsupervised structure learning methods to categorize behaviors in an unbiased fashion.

Human cells and tissue

This node includes

  • the IPSC-derived Organoids testing site at The Neuro (McGill),
  • the Live Human Dorsal Root Ganglion and Spinal Cord Tissue (McGill), and
  • the IPSC-Derived Neuronal Cultures testing site at the CERVO Brain Research Centre.
Read more about the Human cells and tissue testing sites

The IPSC-Derived Neuronal Cultures testing site relies on a team of highly qualified personnel, and comprises a park of multimodal microscopes allowing the high-content label-free testing and optimization of the optogenetic tools that are designed, produced, and packaged by colleagues of the protein engineering and viral vector cores of the COVF . Those tests are conducted on cortical neural networks derived from a biobank of highly phenotyped human induced pluripotent cell lines (hiPSCs).

The IPSC-derived Organoids testing node is part of the Early Drug Discovery Unit (EDDU) at The Neuro. The EDDU specializes in generating different types of brain cells and 3D brain organoids for fundamental and translational discovery, with workflows and the infrastructure available for automation, small molecule screening and single cell phenotyping by flow cytometry. Together with Canadian and international academic and industrial partners, we work with high quality patient-derived, gene-edited, and isogenic control iPSC-derived cells to build new disease-relevant tools and assays for discovery purposes. With a rapidly growing base of both active academic and industry users, the EDDU has grown steadily over the past six years, slowly becoming a hub for training HQP from labs across Canada on everything from iPSCs to discovery assays.

The Live Human Dorsal Root Ganglion and Spinal Cord Tissue is located at McGill. It is equipped for testing viral transduction and optogenetics tools in live human dorsal root ganglion and spinal cord tissue harvested thanks to a partnership between the Alan-Edwards Centre for Research on Pain at McGill and Transplant Quebec through a consortium of organ donors across several hospitals in Montreal.

Rodents

This node includes

  • the Home-Cage Mesoscopic Functional Imaging of Mouse Cortex site (UBC),
  • the Synaptic Release and Plasticity site (University of Ottawa),
  • the Photometry/Optogenetics of Neuroendocrine Signalling testing site (University of Calgary, and
  • the Spinal Optogenetics site at the CERVO Brain Research Centre.
Read more about the rodents testing sites

Located at UBC Djavad Mowafaghian Centre for Brain Health, the home-cage Home-Cage Mesoscopic Functional Imaging of Mouse Cortex site provides an in vivo testing platform specializing in fiber photometry, which allows probes to be assessed in specific brain regions/nuclei during behavioral engagement, in addition to expertise in mesoscale cortical widefield imaging. We combine these imaging techniques with automated home cage motor assessment to provide high throughput testing of new reagents and animal phenotyping in models of human neurological disease.  New infrastructure in 2022 will expand our testing node to include new modalities: 3-photon imaging and mesoscale cellular imaging with ultra-wide field of view 2-photon imaging.  A strong training component exists within the NeuroImaging and NeuroComputation Center, where a weekly technology forum — Databinge, meets to discuss and implement data analysis approaches and advanced training.  We are currently working to extend Databinge to a multi-institution platform through interactions with the Canadian Brain Research Strategy, other national groups and our international partners in the International Network for BioInspired Computing (USA, France, Canada).  Recent success in CFI competitions has led to the development of a multi-scale imaging platform termed iMAP that provides testing across multiple scales of resolution. Recent development of open science principles ensure sharing of collected data and increase transparency in research.

Located at the Hotchkiss Brain Research Center (University of Calgary), the Photometry/Optogenetics of Neuroendocrine Signalling facility is composed of an extended team of experts in rodent stereotaxic brain surgery, in vivo validation, fibre photometry using calcium or other biosensors, optogenetic stimulation or inhibition, in vivo cellular calcium imaging and a variety of behavioural procedures and computational methods. The Borgland lab is a member of the optogenetic core facility and has expertise in validating viral vectors using immunohistochemistry, brain slice electrophysiology, and in vivo behavioural models with a focus on reward learning. The Borgland lab is a COVF testing site and has used several viral vector tools disseminated from the Laval core facility to test in rodent in vitro brain slice preparation to test synaptic connectivity and in in vivo behavioural models of reward learning. Results from novel vectors are shared with the COVF team.

Located in uOttawa’s Faculty of Medicine (FOM), the Synaptic Release and Plasticity testing site is part of the Cell Biology and Image Acquisition core (CBIA); (https://med.uottawa.ca/core-facilities/facilities/cbia) it oversees the use and maintenance of several optical imaging systems (eg., Confocal and multiphoton microscopes; STED system; Spinning disk; imaging software; analysis workstations and others). The CBIA facility’s operating budget (>$300K per annum) is based on a partial cost-recovery model, with direct institutional contributions from uOttawa and the FOM that allows competitive user fees to the community. The CBIA facility has a broad mandate, including covering service contracts for major equipment, overseeing a preventative maintenance program, providing optical and imaging training to HQPs and providing funds for the procurement of new instruments or replacement parts. The CBIA is operating under a Planning and Priorities Committee and is staffed by a Senior Imaging specialist and an imaging technician that carry out the day-to-day activity. The Béïque lab will act as the formal contact between this core, uOttawa’s neuroscience community and members of the COVF. His lab has developed expertise in employing cellular electrophysiological techniques in combination with several optical approaches (optogenetics and multiphoton imaging) to study neuronal dynamics over different time scales. The uOttawa testing site will provide experimental testing of viral vectors and optical sensors in rodents both in vivo (cellular imaging in learning tasks by 2P or miniendoscope imaging), and in vitro (electrophysiological calibration of 1 or 2P signals). The performance of the newly developed sensors will be further examined by concurrent advanced analytical and network simulations tools by the computational neuroscientists at uOttawa’s Center for Neural Dynamics.

Located at the CERVO Brain Research Centre (Université Laval), the spinal optogenetics site is composed of an extended team of experts in optogenetics, imaging and electrophysiological approaches in both anaesthetized and freely moving animal. Our goal is to offer to every researcher requiring our help a testing node to certify the efficiency of their hardware or molecular tools for optogenetic experiments. To do so, our core is specialized in the acquisition of calcium signals, optogenetic mediated neuronal manipulation with innovative technologies such as in vivo micro-endoscopy, photometry combined or not with electrophysiological recording. Our expertise allows us to acquire and analyze signal from a wide range of brain regions down to the cellular resolution in rodents. By working in close collaboration with the viral vectors platform we can validate custom-tailored tools before implementation in larger scale experiments thus further nurturing the feedback loop between production site and customers, ensuring the constant improvement of the tools developed.

Non-Human Primates (NHPs)

The COVF Non-Human Primates (marmoset) testing site is located at the Montreal General Hospital (McGill). The objective of this platform is to enable access to advanced animal modeling for understanding and decoding neural circuit function in the primate brain.

Read more about the Non-Human Primates testing site

The facility allows access to cutting-edge in vivo infrastructure and technical know-how for McGill, Canadian, and international researchers engaged in neurophysiology, neuroimaging, behavioural analysis, and disease modeling to effect meaningful translational neuroscience research. A main goal of the platform is to close the ‘translational gap’ between rodent and human species through the utilization of the common marmoset (Callithrix jacchus) model. The complex brain anatomy, cognition, and behaviour of marmosets and their amenability for genetic engineering make them a powerful model for understanding brain activity underlying behaviour and for confronting brain disorders/diseases. The MGH platform is making accessible cutting-edge viral delivery approaches and in vivo cellular imaging using miniscope hardware in marmosets. Coupled to the marmoset imaging aspect of the platform will be the establishment of neurophenotyping capacity involving behavioural testing, movement tracking, and pharmacokinetic analysis for drug studies. Furthermore, the platform is also developing services for robotic brain injections, magnetic resonance imaging, and pharmacokinetic analysis in marmosets. Thus, the MGH testing site has important capacity for investigating neural activity in the primate brain using optogenetic tools developed by COVF and offers unique services that do not exist elsewhere in Canada.

COVF Production cores

Protein engineering core

Viral vector core

Specialty fibre-optics core

Focused ultrasound core

Viral Vector Core

(Université Laval, CERVO), The Viral Vector Core is composed of an extended team of experts specializing in molecular biology, tissue culture, in vivo validation, microscopy, flow cytometry and process optimization. Working closely with experts from across the globe, we offer the highest-quality vectors that can be custom-tailored to meet almost any vectorology-based research need.  Our developers identify new specific promoters and AAV capsids, and collaborate with experts in optogenetics. We work synchronously with dedicated teams of researchers from the different COVF testing sites, covering a spectrum of animal models. This constant communication ensures the continuous improvement of molecular throughout their development.

Read more about this core

Protein engineering core

(Laval University, University of Tokyo) The mission of the Protein Engineering Core is to create customized, high-performance, and well-characterized optogenetic tools that are optimized for end-user applications. We aim to make these tools widely available for the global research community to advance neuroscience research, accelerate therapeutic development, and enable biological discoveries. We leverage our knowledge, expertise, and experience in protein engineering, to design, develop, distribute, and democratize optogenetic tools for neuroscience, cell biology, and across all areas of biological research. The Protein Engineering Core seamlessly integrates with the Viral Vector Core to make all of the viral vectors that encode our optogenetics tools available worldwide. We also closely engage the COVF testing nodes for the testing, characterization, and evaluation of optogenetic molecular tools in the development pipeline. We strive to provide an inclusive and synergistic service platform for all researchers and promote two-way education and communication between tool developers and the end-user community.

Read more about this core

Focused Ultrasound Core

Focused ultrasound icon

(Sunnybrook Research Institute, CeRIGT) The Focused Ultrasound (FUS) Core is built on unique expertise, resources, infrastructure, and governance within the only Centre of Excellence in Focused Ultrasound in Canada. This team of experts offers services in FUS applications related to gene delivery. Their leaders specialize in FUS device conception, development, and applications to the brain and spinal cord that are adapted to user needs. They focus on optimizing gene delivery, specifically for AAV, to the central nervous system using FUS. We engage with experts, in academia and industry, to identify and customize tools that are compatible with FUS and optogenetics technologies. We design, plan, and execute FUS experiments, and provide outstanding quality control in tissue processing and high throughput imaging. They collaborate with teams nationally and internationally to continue to improve the tools required for gene delivery applications with FUS.

Read more about this core (outside link – Sunnybrook)

Specialty Fibre Optics Core

(Laval University, COPL) The specialty fibre-optics core specializes in glass material synthesis, optical fiber manufacturing and photonic device development for a variety of technology markets. It is the only university laboratory in Canada that can design and manufacture a wide variety of specialty glass optical fibres and fibre devices. The core has been operating for 13 years during which time has developed partnerships with colleagues in academia and industry world-wide. These relationships have led to a consistent customer base with requests including customized specialty glass preforms and optical fibres for a variety of manufacturing and R&D needs. Within the COVF, the Specialty Fibre-optics core works very closely with the Optogenetics Engineering and Testing cores to deploy and optimize fibre-based optrodes for opto-electrical stimulation and sensing on very localized volumes of tissue. These unique optrodes allow for efficient neurochemical and ion sensing applicable to the wide variety of animal species covered by the COVF testing nodes.

Read more about this core

COVF Selected Publications

Recent publications using COVF developed tools

  • S. M. Cain et al., “Hyperexcitable superior colliculus and fatal brainstem spreading depolarization in a model of sudden unexpected death in epilepsy,” Brain Communications, 2022, doi: 10.1093/braincomms/fcac006.
  • B. S. Bono, N. K. K. Ly, P. A. Miller, J. Williams‐Ikhenoba, Y. Dumiaty, and M. J. Chee, “Spatial distribution of beta‐klotho mRNA in the mouse hypothalamus, hippocampal region, subiculum, and amygdala,” Journal of Comparative Neurology, 2022, doi: 10.1002/cne.25306.
  • M. Bérard et al., “A light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease,” PLoS Biology, vol. 20, no. 3, p. e3001578, 2022, doi: 10.1371/journal.pbio.3001578.
  • G. P. Shelkar, J. Liu, and S. M. Dravid, “Astrocytic NMDA receptors in the basolateral amygdala contribute to facilitation of fear extinction,” International Journal of Neuropsychopharmacology, pp. pyab055-, 2021, doi: 10.1093/ijnp/pyab055.
  • A. Servonnet, P.-P. Rompré, and A.-N. Samaha, “Optogenetic activation of basolateral amygdala projections to nucleus accumbens core promotes cue-induced expectation of reward but not instrumental pursuit of cues,” bioRxiv, p. 2021.10.20.465037, 2021, doi: 10.1101/2021.10.20.465037.
  • P.-L. Rochon, C. Theriault, A. G. R. Olguin, and A. Krishnaswamy, “The cell adhesion molecule Sdk1 shapes assembly of a retinal circuit that detects localized edges,” eLife, vol. 10, p. e70870, 2021, doi: 10.7554/elife.70870.
  • Y. Nasu et al., “A genetically encoded fluorescent biosensor for extracellular L-lactate,” 2021, doi: 10.1101/2021.03.05.434048.
  • E. Bourinet, M. Martin, D. Huzard, F. Jeanneteau, P.-F. Mery, and A. François, “The impact of C-Tactile Low threshold mechanoreceptors on affective touch and social interactions in mice,” bioRxiv, p. 2021.01.13.426492, 2021, doi: 10.1101/2021.01.13.426492.
  • G. Bilodeau et al., “A Wireless Electro-Optic Platform for Multimodal Electrophysiology and Optogenetics in Freely Moving Rodents,” Frontiers in Neuroscience, vol. 15, p. 718478, 2021, doi: 10.3389/fnins.2021.718478.
  • L. Tenorio-Lopes, S. Fournier, M. S. Henry, F. Bretzner, and R. Kinkead, “Disruption of estradiol regulation of orexin neurons: a novel mechanism in excessive ventilatory response to CO2 inhalation in a female rat model of panic disorder,” Transl Psychiatry, vol. 10, no. 1, p. 394, Nov. 2020, doi: 10.1038/s41398-020-01076-x.
  • Y. Shen, R. E. Campbell, D. C. Côté, and M.-E. Paquet, “Challenges for Therapeutic Applications of Opsin-Based Optogenetic Tools in Humans,” Frontiers in Neural Circuits, vol. 14, p. 41, 2020, doi: 10.3389/fncir.2020.00041.
  • B. Sharif, A. R. Ase, A. Ribeiro-da-Silva, and P. Séguéla, “Differential Coding of Itch and Pain by a Subpopulation of Primary Afferent Neurons,” Neuron, vol. 106, no. 6, pp. 940-951.e4, 2020, doi: 10.1016/j.neuron.2020.03.021.
  • K. Servick, “Controlling monkey brains with light could get easier thanks to open data project Optogenetic tools refined in rodents have been tricky to use in nonhuman primates,” Science, 2020, doi: doi: 10.1126/science.abf4696.
  • C. Salesse et al., “Opposite Control of Excitatory and Inhibitory Synapse Formation by Slitrk2 and Slitrk5 on Dopamine Neurons Modulates Hyperactivity Behavior,” Cell Reports, vol. 30, no. 7, pp. 2374-2386.e5, 2020, doi: 10.1016/j.celrep.2020.01.084.
  • M. A. K. Sagar, J. N. Ouellette, K. P. Cheng, J. C. Williams, J. J. Watters, and K. W. Eliceiri, “Microglia activation visualization via fluorescence lifetime imaging microscopy of intrinsically fluorescent metabolic cofactors,” Neurophotonics, vol. 7, no. 03, p. 1, 2020, doi: 10.1117/1.nph.7.3.035003.
  • T. Patriarchi et al., “An expanded palette of dopamine sensors for multiplex imaging in vivo,” Nature Methods, vol. 17, no. 11, pp. 1147–1155, 2020, doi: 10.1038/s41592-020-0936-3.
  • C. S. Khademullah et al., “Cortical interneuron-mediated inhibition delays the onset of amyotrophic lateral sclerosis,” Brain, vol. 143, no. 3, pp. 800–810, 2020, doi: 10.1093/brain/awaa034.
  • F. Cao et al., “Neuroligin 2 regulates absence seizures and behavioral arrests through GABAergic transmission within the thalamocortical circuitry,” Nature Communications, vol. 11, no. 1, p. 3744, 2020, doi: 10.1038/s41467-020-17560-3.
  • O. Ayad et al., “In vitro differentiation of W8B2+ human cardiac stem cells: gene expression of ionic channels and spontaneous calcium activity,” Cellular & Molecular Biology Letters, vol. 25, no. 1, p. 50, 2020, doi: 10.1186/s11658-020-00242-9.
  • D. Agudelo et al., “Versatile and robust genome editing with Streptococcus thermophilus CRISPR1-Cas9,” Genome Research, vol. 30, no. 1, pp. 107–117, 2020, doi: 10.1101/gr.255414.119.
  • A. K. Yang, J. A. Mendoza, C. K. Lafferty, F. Lacroix, and J. P. Britt, “Hippocampal Input to the Nucleus Accumbens Shell Enhances Food Palatability,” Biological Psychiatry, vol. 87, no. 7, pp. 597–608, 2019, doi: 10.1016/j.biopsych.2019.09.007.
  • Y. Qian et al., “A genetically encoded near-infrared fluorescent calcium ion indicator,” Nature Publishing Group, vol. 16, no. 2, pp. 1–12, Jan. 2019, doi: 10.1038/s41592-018-0294-6.
  • H. Petitjean et al., “Recruitment of Spinoparabrachial Neurons by Dorsal Horn Calretinin Neurons,” CellReports, vol. 28, no. 6, pp. 1429-1438.e4, Aug. 2019, doi: 10.1016/j.celrep.2019.07.048.
  • M. Mouchiroud et al., “Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis,” Molecular Metabolism, vol. 30, pp. 184–191, 2019, doi: 10.1016/j.molmet.2019.09.014.
  • N. J. Michelson, M. P. Vanni, and T. H. Murphy, “Comparison between transgenic and AAV-PHP.eB-mediated expression of GCaMP6s using in vivo wide-field functional imaging of brain activity,” Neurophotonics, vol. 6, no. 02, p. 1, 2019, doi: 10.1117/1.nph.6.2.025014.
  • J. A. Mendoza, C. K. Lafferty, A. K. Yang, and J. P. Britt, “Cue-Evoked Dopamine Neuron Activity Helps Maintain but Does Not Encode Expected Value,” Cell Reports, vol. 29, no. 6, pp. 1429-1437.e3, 2019, doi: 10.1016/j.celrep.2019.09.077.
  • J. Liu, G. P. Shelkar, F. Zhao, R. P. Clausen, and S. M. Dravid, “Modulation of Burst Firing of Neurons in Nucleus Reticularis of the Thalamus by GluN2C-Containing NMDA Receptors,” Molecular Pharmacology, vol. 96, no. 2, pp. 193–203, 2019, doi: 10.1124/mol.119.116780.
  • D. Agudelo et al., “Versatile and robust genome editing with Streptococcus thermophilus CRISPR1-Cas9,” bioRxiv, p. 321208, 2019, doi: 10.1101/321208.
  • N. Josset, M. Roussel, M. Lemieux, D. Lafrance-Zoubga, A. Rastqar, and F. Bretzner, “Distinct Contributions of Mesencephalic Locomotor Region Nuclei to Locomotor Control in the Freely Behaving Mouse,” Current Biology, vol. 28, no. 6, pp. 884-901.e3, Mar. 2018, doi: 10.1016/j.cub.2018.02.007.
  • P. L. W. Colmers and J. S. Bains, “Presynaptic mGluRs Control the Duration of Endocannabinoid-Mediated DSI,” Journal of Neuroscience, vol. 38, no. 49, pp. 10444–10453, 2018, doi: 10.1523/jneurosci.1097-18.2018.
  • K. T. Barrett, A. Roy, K. B. Rivard, R. J. A. Wilson, and M. H. Scantlebury, “Vagal TRPV1 activation exacerbates thermal hyperpnea and increases susceptibility to experimental febrile seizures in immature rats,” Neurobiology of Disease, vol. 119, pp. 172–189, Nov. 2018, doi: 10.1016/j.nbd.2018.08.004.
  • A. Chabrat et al., “Transcriptional repression of Plxnc1 by Lmx1a and Lmx1b directs topographic dopaminergic circuit formation.,” Nature Communications, vol. 8, no. 1, p. 933, Oct. 2017, doi: 10.1038/s41467-017-01042-0.
  • H. Beaudry, I. Daou, A. R. Ase, A. Ribeiro-da-Silva, and P. Séguéla, “Distinct behavioral responses evoked by selective optogenetic stimulation of the major TRPV1+ and MrgD+ subsets of C-fibers.,” Pain, vol. 158, no. 12, pp. 2329–2339, Dec. 2017, doi: 10.1097/j.pain.0000000000001016.
  • H. Doucet-Beaupré et al., “Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons.,” Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 30, pp. E4387-96, Jul. 2016, doi: 10.1073/pnas.1520387113.
  • P. Chapdelaine et al., “Development of an AAV9 coding for a 3XFLAG-TALEfrat#8-VP64 able to increase in vivo the human frataxin in YG8R mice.,” Gene therapy, vol. 23, no. 7, pp. 606–614, Jul. 2016, doi: 10.1038/gt.2016.36.
  • H. Petitjean et al., “Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury.,” CellReports, vol. 13, no. 6, pp. 1246–1257, Nov. 2015, doi: 10.1016/j.celrep.2015.09.080.

Canadian Optogenetics & Vectorology Foundry

Optogenetics is revolutionizing neuroscience and mental health from basic science to clinical applications. The Canadian Optogenetics and Vectorology Foundry (COVF) is a national facility at the heart of a worldwide effort to accelerate the development, production, dissemination, and use of genetically encoded light-activated tools.

Our biofoundry model responds to tool Design-Build-Test requests, accelerates translation across species, experimental paradigms and disease models, and aims to support porting optogenetics to clinical applications via gene transfer approaches. Our services also include consulting and training to democratize optogentics and viral vector technologies, especially Adeno-Associated Viral Vectors (AAVs) for neuroscience and beyond.


COVF’s operations are based on four Production Cores that are coupled to Testing Nodes across the country involved in tool characterization and validation.

Learn more about our organizational structure and the talented people involved.

Access publications highlighting the exciting research being conducted at COVF.

Follow along as our program evolves and our teams make exciting new discoveries.

Explore our Core technologies – Watch!

Researchers at Sunnybrook Research Institute are developing a non-invasive, reversible, and targeted procedure to breach the blood-brain barrier through the use of focused ultrasound and microbubbles. Watch the video on the left to learn more about this cutting-edge technique.

There are 3 technologies at the very core of the COVF: Protein Engineering, Viral Vectors, and Specialty Fibre-Optics. Watch the video on the right to learn more about these amazing tools.

Partner institutions

partner institution logos

 

Funders

Funders logos

COVF Specialty Optical Fibers

COVF Specialty Optical Fibers

COPL’s optical fiber fabrication research teams have developed an unparalleled know-how: from glass design, to MCVD preform synthesis, to the drawing of specialty optical fibers. Discover our infrastructure and the different types of optical fibers drawn in our facilities. Fiber compositions, geometries and guiding properties can be customized to fit your needs and applications.

Contact us to discuss the feasibility of your project: copl@copl.ulaval.ca

Infrastructure

MCVD process

  • Silica preform synthesis
  • Vapour phase deposition
  • Doping (Ge, P, Al) for index control
  • Doping (Er, Yv, Nd, Th, etc. for active fibers

Silica fiber drawing tower

  • For silica fibers

Drawing tower – Other materials

  • 4 furnaces covering a wide range of transition temperatures
  • For polymers, chalcogenides, tellurites, phosphates, silicophosphates, etc.

Sample achievements

  • Microstructured
  • Multiple-core
  • Graded-index
  • Multimaterial

Process Flow Chart

Process flow chart

COVF – Vectorology Core

Viral Vector Tools

Click here to order viral vectors

Viral vectors are the vehicles of choice to deliver genetically encoded tools to living cells in culture or in a live animal. They are modified viruses from which pathogenic sequences have been removed and replaced by genes of interest that the user wishes to introduce into cells. As many types of viruses exist, they have led to the development of various vectors with different characteristics (type of genome, genome length, enveloped or not, specific tropism etc.). Vectors based on Adeno Associated Viruses (AAVs) have been used extensively in neuroscience research and other fields as well as for human clinical applications. Their complete lack of pathogenicity associated with their ability to transduce non-dividing cells and relative ease of production have contributed to their success. Other viral vector types include Retroviruses, Human and Canine Adenoviruses, Rabies Viruses and Lentiviruses…

Vectorology Core

Located at the CERVO Brain Research Center (Université Laval), the group is led by Marie-Eve Paquet and composed of an extended team of experts in molecular biology, tissue culture, in vivo validation, microscopy, flow cytometry and process optimization. We strive to offer Canadian researchers the best quality vectors possible adapted to their needs. With that in mind, we work closely with a worldwide community of tools developers including those identifying new specific promoters, improved AAV capids, as well as experts in optogenetics such as our colleagues from the Protein Engineering Core.

The vectorology core has numerous distribution agreements with tool developers to disseminate optogenetic and viral tools.

map of distribution agreements - vectorology core

History of the vectorology core

Our Mission

The mission of the Vectorology Core is to make viral delivery tools widely available for the worldwide research community to catalyze advances in basic neuroscience and therapeutic development. With a focus on end-user needs, we are heavily involved in the development of custom tools and strategies. Together with the testing nodes of the COVF, we are also engaged in facilitating the validation of light sensitive and viral tools.

The viral vector core distributes molecular tools around the world.

Distribution network of viral vector tools produced by the vectorology core

 

COVF – Protein Engineering core

Optogenetic Molecular Tools

Optogenetic molecular tools are light-responsive proteins that enable the manipulation and visualization of the intricate network of neuronal activities with precise spatiotemporal resolution. Optogenetic actuator proteins are used to activate or inhibit certain cell functions in response to light, while optogenetic indicator proteins change their fluorescent signal output in response to biochemical changes within live cells. Protein engineering is a key technique to convert naturally occurring fluorescent and other light-responsive proteins into useful optogenetic molecular tools for basic neuroscience research and translational therapeutic applications.

Optogenetic indicators - Calcium, voltage, transmitter releaseProtein Engineering Core

The Campbell laboratory at the University of Alberta is at the origin of the Protein Engineering Core of the Canadian Optogenetics and Vectorology Foundry. The laboratory has migrated to the CERVO Brain Research Centre under the form of the CERVO Optogenetic Tool Production Platform (Plateforme de Production d’Outils Optogénétique du Centre CERVO – PPOOCC) and is fully operational. The PPOOCC leverages our knowledge, expertise, and experience in protein engineering, to design and develop novel optogenetic tools with highly optimized performance. We also work closely with a Canada-wide community of neuroscience researchers to test, characterize, and evaluate the optogenetic molecular tools in the development pipeline.

Projects in development

Our diverse project portfolio includes:

Fluorescent proteins

  • Optogenetic indicator proteins for neuronal activities including Ca2+ entry, membrane voltage change, and synaptic transmission.
  • Optogenetic indicator proteins for metabolites and cellular metabolic status.
  • Optogenetic indicator proteins with red and near-infrared fluorescence.
  • Optogenetic activator proteins to control cellular function by light-induced protein cleavage.
  • Optogenetic actuator proteins for controlling cellular functions via light-induced protein cleavage.

Open Science

We are strong believers in open and collaborative science. All the DNA plasmid reagents developed from the Protein Engineering Core will be available through the nonprofit plasmid repository Addgene Addgene: Robert Campbell Lab Plasmids.

The Protein Engineering Core vertically integrates with the Molecular Tools Platform of the Canadian Optogenetics and Vectorology Foundry, hence all viral vectors encoding our optogenetics tools will be available through the molecular tools platform Canadian Neurophotonics Platform – Viral Vector Core.

We strive to provide an inclusive and synergistic platform for all forms of collaborations and promote two-way education in the community of tool developers and end-users. If you wish to test new optogenetic tools or have any related questions, please don’t hesitate to contact us at robert.e.campbell@ualberta.ca or yi.shen@ualberta.ca.

Our Mission

The mission of the Protein Engineering Core is to craft custom-designed, high-performance, and well-characterized optogenetic tools that are optimized for end-user applications, and make these tools widely available for the worldwide research community to catalyze advances in neuroscience research and therapeutic development.