Innovative Projects Realized

Liquid biopsy for the discovery of new methods of cancer diagnosis and new treatment strategies – Year two

Despite the improvements in cancer diagnostic and treatment, cancer is still a leading cause of death in Canada with 30% of all deaths. Some cancers, like pancreatic cancer (PC), still have poor survival rates due to the lack of early diagnosis and good prognostics markers. The Atlantic Cancer Research Institute (ACRI) has developed a proprietary technology to capture extracellular vesicles (EVs) from various biofluids with the goal to deliver precision medicine solutions through liquid biopsy technologies. Cancer cells are known to secrete EVs that carry almost every cell molecular components. This project aims to compare many components of EVs captured in plasma from cancer patients and healthy controls. The main goals of this project are to establish particular disease biosignatures and to evaluate their potential to detect and identify cancers earlier, and to evaluate the efficiency of the treatments by monitoring cancer progression. This could result in significant economic benefits for our health care systems by making sure the treatment is right for the patient and by halting expensive treatments for non-responders sooner. This represents a business opportunity if health care systems or diagnostic companies form a partnership with ACRI for the diagnosis and monitoring of cancer patients.

Liquid biopsy for the discovery of new methods of cancer diagnosis and new treatment strategies

Despite the improvements in cancer diagnostic and treatment, cancer is still a leading cause of death in Canada with 30% of all deaths. Some cancers, like pancreatic cancer (PC), still have poor survival rates due to the lack of early diagnosis and good prognostics markers. The Atlantic Cancer Research Institute (ACRI) has developed a proprietary technology to capture extracellular vesicles (EVs) from various biofluids with the goal to deliver precision medicine solutions through liquid biopsy technologies. Cancer cells are known to secrete EVs that carry almost every cell molecular components. This project aims to compare many components of EVs captured in plasma from cancer patients and healthy controls. The main goals of this project are to establish particular disease biosignatures and to evaluate their potential to detect and identify cancers earlier, and to evaluate the efficiency of the treatments by monitoring cancer progression. This could result in significant economic benefits for our health care systems by making sure the treatment is right for the patient and by halting expensive treatments for non-responders sooner. This represents a business opportunity if health care systems or diagnostic companies form a partnership with ACRI for the diagnosis and monitoring of cancer patients.

Fluoride Removal from Brine Solutions

NORAM Engineering and Constructors have a technology called salt splitting. This technology is used to produce caustic soda and sulfuric acid. However, the presence of fluoride in this technology can cause the breakdown of the coating on the titanium anode, which can cause premature anode failure. As replacing these titanium anodes can incur significant costs, purification in this technology to reduce its fluoride concentration is imperative. This project therefore seeks to obtain the fundamental understandings of this mechanism on the fluoride removal by using ion exchange resin, and potentially mitigate this technical challenge.

Natural products for Spotted Wing Drosophila (SWD) pest management

Spotted Wing Drosophila is an aggressive invasive pest that is high research and management priority for the BC and Canadian berry and small fruit industry. Spotted Wing Drosophila can substantially reduce crop yields despite heavy uses of chemical insecticides, which in some cases can be harmful to the environment and human health. Botanical extracts from plants and insecticidal microbes that are naturally toxic to insects have great potential to provide enviromentally-friendly options for growers to manage Spotted Wing Drosophila. The proposed research will evaluate botanical extracts from the Neem tree, Azadirachta indica, and from the Pongamia pinnata (Karanja) tree, and plant and soil associated microbial isolates for insecticidal and pest repellent effects in collaboration with Terramera Inc. We will evaluate oil extracts from these trees, specifically Neem and Karanaja oil, and screen microbial isolates for their compatibility with Spotted Wing Drosophila biological control agents, including Bacillus thuringiensis. We will determine the specific effects of these natural products, including their lethal and sub-lethal effects, on Spotted Wing Drosophila in the lab, greenhouse and field.

Improving avalanche forecasts in data-sparse areas with physical snowpack modelling – Year two

Assessing dangerous avalanche conditions requires a reliable stream of weather and snowpack data, which can be difficult and expensive to collect in many remote areas of Canada. Snowpack conditions can be simulated in these areas by coupling weather forecast models with physical snowpack models, however, this method has had limited adoption by avalanche forecasters. The proposed project will increase the adoption of snowpack models by developing a dashboard that allows Avalanche Canada forecasters to visualize spatial snowpack patterns, alarm them of critical changes, and provide an assessment of the model’s accuracy. Novel methods of comparing model output with snow observations will be investigated and spatial clustering methods will offer a new dynamic view of regional snowpack patterns. The project will improve the accuracy and quality of Avalanche Canada’s public safety products and warnings in data-sparse areas.

Improving avalanche forecasts in data-sparse areas with physical snowpack modelling

Assessing dangerous avalanche conditions requires a reliable stream of weather and snowpack data, which can be difficult and expensive to collect in many remote areas of Canada. Snowpack conditions can be simulated in these areas by coupling weather forecast models with physical snowpack models, however, this method has had limited adoption by avalanche forecasters. The proposed project will increase the adoption of snowpack models by developing a dashboard that allows Avalanche Canada forecasters to visualize spatial snowpack patterns, alarm them of critical changes, and provide an assessment of the model’s accuracy. Novel methods of comparing model output with snow observations will be investigated and spatial clustering methods will offer a new dynamic view of regional snowpack patterns. The project will improve the accuracy and quality of Avalanche Canada’s public safety products and warnings in data-sparse areas.

Interaction between cannabinoid drugs and sodium channels in diabetes/high glucose induced oxidative stress, neuroinflammation, and neurotoxicity – Year two

Diabetes mellitus, a common metabolic disorder, exhibits neuropathic complications that can eventually lead to disabling pain (Todorovic 2015). This is attributed to hyperglycemia/high glucose resulting in neuronal hyperexcitability (Todorovic 2015). Importantly, diabetes-evoked neuronal hyperexcitability and neurotoxicity can be caused by alterations in voltage-gated sodium channel (VGSC) expression (Hong, Morrow et al. 2004), resulting in changes in the sodium currents lowering the action potential threshold (Hong, Morrow et al. 2004, Chen, Wang et al. 2018). Interestingly, cannabinoids exert antinociceptive properties. In addition, both cannabinoid receptors, CB-1 and CB-2, are highly expressed in central and peripheral nervous systems, suggesting a fundamental role in nociception (Agarwal, Pacher et al. 2007, Rahn and Hohmann 2009). Also, estrogen (E2) loses its neuroprotective effect, or worsens neuronal injury in diabetic animals (Santizo, Xu et al. 2002). Thus, the current study aims to investigate the role of VGSC in high glucose-induced neurotoxicity, and whether high glucose modulation of VGSC can be altered using cannabinoids. Also, this study will investigate sex-determined modulation of cannabinoid/VGSC interaction in high glucose elicited neurotoxicity. Noteworthy, our results may identify novel molecular targets for alleviating neuropathic pain and solve the sex-specific exacerbation of neurological dysfunction elicited by diabetes.

Méthodologie de conception, vérification, et test des systèmes embarquéstolérants aux radiations

STAGIAIRE1 (PhD1, ISR) Génération et propagation des requis de conception vers le

sous-système électronique embarqué.

Les objectifs spécifiques du projet de l’étudiant PhD1 (tâches 1.1 et 1.2 du projet global)

sont : 1) l’élaboration, la mise en oeuvre et la validation d’une stratégie permettant de

déterminer la robustesse inhérente des autres éléments du système global, afin de définir les

spécifications de fiabilité au niveau du sous-système embarqué, et 2) l’élaboration, la mise en

oeuvre et la validation d’une stratégie permettant de déterminer les requis de

fiabilité/robustesse des diverses parties de l’application embarquée au niveau sous-système,

à partir de ceux identifiés au niveau système. Ces requis de robustesse seront par la suite

utilisés pour guider le partitionnement et le choix des circuits (rad-hard versus non rad-hard)..

Le partenaire industriel, ISR, va fournir des exemples (modèles) de sous-systèmes. Ces

modèles seront utilisés comme cas d’étude par l’étudiant pendant son stage. L’étudiant aura

également accès aux concepteurs de ces modèles. En contrepartie, la compagnie va…………………………………….

Interaction between cannabinoid drugs and sodium channels in diabetes/high glucose induced oxidative stress, neuroinflammation, and neurotoxicity

Diabetes mellitus, a common metabolic disorder, exhibits neuropathic complications that can eventually lead to disabling pain (Todorovic 2015). This is attributed to hyperglycemia/high glucose resulting in neuronal hyperexcitability (Todorovic 2015). Importantly, diabetes-evoked neuronal hyperexcitability and neurotoxicity can be caused by alterations in voltage-gated sodium channel (VGSC) expression (Hong, Morrow et al. 2004), resulting in changes in the sodium currents lowering the action potential threshold (Hong, Morrow et al. 2004, Chen, Wang et al. 2018). Interestingly, cannabinoids exert antinociceptive properties. In addition, both cannabinoid receptors, CB-1 and CB-2, are highly expressed in central and peripheral nervous systems, suggesting a fundamental role in nociception (Agarwal, Pacher et al. 2007, Rahn and Hohmann 2009). Also, estrogen (E2) loses its neuroprotective effect, or worsens neuronal injury in diabetic animals (Santizo, Xu et al. 2002). Thus, the current study aims to investigate the role of VGSC in high glucose-induced neurotoxicity, and whether high glucose modulation of VGSC can be altered using cannabinoids. Also, this study will investigate sex-determined modulation of cannabinoid/VGSC interaction in high glucose elicited neurotoxicity. Noteworthy, our results may identify novel molecular targets for alleviating neuropathic pain and solve the sex-specific exacerbation of neurological dysfunction elicited by diabetes.

Silicon Quantum Dot Trace Explosive Sensor – Year two

The rapid detection of high energy materials (i.e., explosives) and chemical, biological and radioactive (CBR) agents have received substantial attention because of its obvious importance to security and forensics. Applied Quantum Materials Inc. (AQM) is developing a straightforward luminescent quantum dot paper- and/or cloth-based detection system that shows instantaneous optical detection of nitro-based explosives in solution and solid phases at nanogram levels by monitoring the luminescence quenching after being exposed to explosive residues.

The issue at hand is the current quantum dot (QD) sensor cannot distinguish between different nitro-based explosive groups (i.e., nitroaromatics, nitramines, and nitrate esters). Furthermore, the current technology cannot detect explosive inorganic salts (i.e., nitrate- and chlorate-based). The Research Intern will be responsible for working with AQM and its partners to develop and test the capabilities of the AQM QD sensor for its selectivity and the initial basic research for the development of new sensors for the detection of inorganic salts and chemical warfare agents. The sensors will be tested for their applications for first responders in the field, border control, and aviation security.

Silicon Quantum Dot Trace Explosive Sensor

The rapid detection of high energy materials (i.e., explosives) and chemical, biological and radioactive (CBR) agents have received substantial attention because of its obvious importance to security and forensics. Applied Quantum Materials Inc. (AQM) is developing a straightforward luminescent quantum dot paper- and/or cloth-based detection system that shows instantaneous optical detection of nitro-based explosives in solution and solid phases at nanogram levels by monitoring the luminescence quenching after being exposed to explosive residues.

The issue at hand is the current quantum dot (QD) sensor cannot distinguish between different nitro-based explosive groups (i.e., nitroaromatics, nitramines, and nitrate esters). Furthermore, the current technology cannot detect explosive inorganic salts (i.e., nitrate- and chlorate-based). The Research Intern will be responsible for working with AQM and its partners to develop and test the capabilities of the AQM QD sensor for its selectivity and the initial basic research for the development of new sensors for the detection of inorganic salts and chemical warfare agents. The sensors will be tested for their applications for first responders in the field, border control, and aviation security.

Enabling next generation cardiac therapeutics with genetic engineering and novel in vivo models for cardiomyocyte transplantation – Year two

The development of cellular therapeutics is acutely dependent on the ability to evaluate the functional characteristics of the cells in predictive animal models. This forms the basis of key pre-clinical data packages that are key for regulatory submissions preceding human clinical trials. The development of appropriate model systems, the execution of the surgical techniques to deliver cells to the target tissue, and the techniques to functionally analyze these cells in situ are technically challenging. Michael Laflamme’s laboratory is focussed on the development of protocols for making and testing human stem cell derived cardiomyocytes in animal models and is the world leader in this field. BlueRock Therapeutics (BRT) is actively developing a clinical and commercial pipeline of cell therapies for cardiac indications. This proposal bridges development work being done in the Laflamme lab and at BRT. The data that will be generated in the project will be instrumental in shaping BRT’s development pipeline. Further, the project will provide Wahiba, the proposed trainee, with an opportunity to work with BRT staff to propose a business case and implementation plan for the internalization of this highly specialized skill set within the company.