Image credit: Francine Nault
Blog Archives
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).
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.
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.
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.
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.
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.
Focused Ultrasound Core
(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.
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
Funders
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
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.
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.
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.
Protein 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:
- 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.