Projets novateurs réalisés

Development of a next-generation in vivo human gene-editing therapeutic platform

The over-arching goal of our project is to develop a robust next-generation gene-editing platform to repair the deleterious mutations that are responsible for genetic diseases such as Cystic Fibrosis and cancer. First-generation precision endonuclease technologies have been tremendous for in vitro gene disruption studies and ex vivo treatments, but there has been limited success at developing safe and effective in vivo human gene-editing therapies. To address these issues, we propose to package a highly specific RNA-guided dual nuclease technology (TevCas9), into liposomal delivery vehicles developed by Specific Biologics Inc. (SBI). By combining these technologies, we will create a powerful therapeutic platform that fulfills the target product profile for an ideal in vivo gene-editing platform. As proof-of-principal, we propose to target and repair the CFTR delta F508 mutation, a monogenetic mutation that results in Cystic Fibrosis (CF) and in which >85% of CF patients carry at least one copy of the mutation. CF was chosen as our model due to the high unmet medical needs of these patients and the suitability of SBI’s proposed liposomal (lipid-based) delivery system to target cells of the respiratory mucosa through nebulization. However, following our initial studies TevCas9 will be retargeted to other clinically relevant targets.

Motion and Attenuation Correction for PET/MRI

During a medical imaging exam, patient motion such as breathing, cardiac motion, and random adjustments of the head or body can affect the accuracy of the acquired images. Positron emission tomography (PET) is a powerful medical imaging technology that can detect minute amounts of an injected probe targeting specific tissue processes and diseases. Magnetic resonance imaging (MRI) can acquire anatomical and functional images of the body, including information about patient motion. Using a hybrid positron emission tomography and magnetic resonance imaging (PET/MRI) system, we are developing better ways to account for motion and attenuation during a PET acquisition using simultaneously acquired MRI data. This work will establish the value of our partner organization’s existing motion correction methods for PET/MRI in various diseases and develop a new PET/MRI method that corrects for cardiac and respiratory motion.

Optimization of small-scale anaerobic digesters for on-site organic waste processing

Anaerobic digestion (AD) is a microbial process where organic materials (sugars, starches, hemicellulose, etc) are broken down into renewable natural biogas and nutrient-rich biodigestate byproducts (roughly 5-10% solids in water). The performance of AD systems is heavily dependent on careful control of digester conditions, including pH, temperature, and health and proportions of the bacterial populations present, which are easily affected by varying characteristics of the waste input stream. CCI BioEnergy currently uses a large-scale AD-based system to convert municipal green bin organic compost into renewable biofuels; however, they aim to optimize low-maintenance, robust and efficient smaller-scale systems for processing at the waste source (eg. residential, commercial, and industrial organic waste producers), allowing for on-site natural gas production and use. One of the expected issues is that compared to municipal waste, on-site waste will be more variable on a day-to-day basis while also potentially lacking overall nutritional profile variety. This project aims both to characterize the performance of digester systems fed from different waste sources, with a particular focus on profiling biological diversity, and to use that information to develop bacterial inoculants to be used in site-specific AD systems to mitigate problems and differences in performance arising from varying waste compositions.

Impact de l’ajout de granulats bitumineux recyclés sur le vieillissement des enrobés

Le recyclage des enrobés bitumineux gagne en popularité. Cette procédure permet de réhabiliter les chaussées flexibles dans un esprit de développement durable. Ce projet de recherche porte sur l’influence d’ajout de granulats bitumineux recyclés (GBR) dans des enrobés neufs. Plus précisément, l’impact de l’ajout de GBR sur la rigidité et sur la résistance à fatigue à long terme sera étudié. Pour ce faire, des essais de module complexe sur des enrobés avec et sans GBR seront effectués sur des éprouvettes ayant subi un vieillissement artificiel en laboratoire. Des essais de résistance à la fatigue avec et sans GBR avant et après vieillissement seront également effectués.

Les Chimiokines : Une nouvelle approche thérapeutique pour le traitementde la douleur.

Les chimiokines sont de petites protéines solubles appartenant à la famille des cytokines dont leurs

principales fonctions sont l’attractivité et l’activation des cellules immunes. De récentes évidences

suggèrent que certains membres de cette famille, dont MCP-1, sécrété au cours de la phase

inflammatoire, ainsi que son récepteur CCR2, seraient également impliqués dans la genèse et le

maintient des douleurs chroniques. Ces protéines largement exprimées dans le système nerveux

participeraient activement à la transmission de l’information nociceptive au niveau périphérie et

modulaire. L’objectif de ce projet de recherche consistera à déterminer le rôle de l’interaction du

ligand MCP-1 à son récepteur CCR2 dans les mécanismes moléculaires, cellulaires et

électrophysiologiques conduisant à la douleur chronique de type inflammatoire. Cette compréhension

amènera à évaluer si l’inhibition pharmacologique ou génique de cette interaction représente une cible

thérapeutique potentielle pour le traitement des douleurs chroniques.

Les deux étudiants gradués seront supervisés par le Dr Stéphane Dion au sein de l’entreprise Pfizer

Inc….

Going On-line with Cognitive Rehabilitation: Testing and Implementing Web-based Goal Management Training at Clinical and Commercial Levels

Goal Management Training® (GMT) is a Baycrest cognitive intervention that has been studied extensively, applied clinically, and manualized into kits for clinicians that have been commercially available since 2012. GMT targets executive functions, a collection of higher-level abilities involved in planning, organization, strategy, and inhibition. Executive impairment can be seen in normal aging as well as in numerous neurological conditions, including dementia and traumatic brain injury (TBI). GMT is the gold-standard treatment for executive impairment worldwide. As part of further commercialization and dissemination efforts, the in-person GMT protocol has recently been translated into a web-based platform.
This project will test online GMT in groups of individuals experiencing executive impairment, including healthy aging and subjective cognitive impairment, and TBI. GMT will be deployed in real-world clinical practice to further refine the implementation protocols. We will also test the program’s commercial viability, which will be required for broad dissemination, and develop a plan to explore long-term health system-level impacts of this innovation/solution.
There is currently no widely accepted and researched online resource for people with executive impairment. The proposed research will leverage expertise of Cogniciti to fill that gap, reinforcing a partnership to provide Cogniciti clients with evidence-based cognitive training.

Opioid Use in Pediatric-Onset Inflammatory Bowel Disease – Year two

Patients with inflammatory bowel disease (IBD) have an inflamed digestive tract and experience diarrhea, fatigue, and abdominal pain. Youth with IBD are six times more likely to take opioids than youth without IBD. We are currently in the midst of an opioid crisis. In 2016, there were almost 3000 deaths related to opioid use in Canada. This increased to nearly 4000 deaths in 2017. Since 2001, opioid-related deaths have increased by 345% in the United States. IBD patients taking opioids have a poorer quality of life, regardless of how severe their IBD is. I will use health administrative data housed at the Institute for Clinical Evaluative Sciences (ICES) to (1) examine trends in opioid prescriptions for children and young adults with and without IBD; (2) identify characteristics of patients who are more likely to take opioids; and (3) evaluate the impact of opioid use on use of health care services, IBD-related surgeries, addiction services, and death. Understanding patterns and the impact of opioid use will allow for creation of strategies to decrease opioid use in IBD and support ICES in their mission to improve health and health care through data and discovery.

Opioid Use in Pediatric-Onset Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD) have an inflamed digestive tract and experience diarrhea, fatigue, and abdominal pain. Youth with IBD are six times more likely to take opioids than youth without IBD. We are currently in the midst of an opioid crisis. In 2016, there were almost 3000 deaths related to opioid use in Canada. This increased to nearly 4000 deaths in 2017. Since 2001, opioid-related deaths have increased by 345% in the United States. IBD patients taking opioids have a poorer quality of life, regardless of how severe their IBD is. I will use health administrative data housed at the Institute for Clinical Evaluative Sciences (ICES) to (1) examine trends in opioid prescriptions for children and young adults with and without IBD; (2) identify characteristics of patients who are more likely to take opioids; and (3) evaluate the impact of opioid use on use of health care services, IBD-related surgeries, addiction services, and death. Understanding patterns and the impact of opioid use will allow for creation of strategies to decrease opioid use in IBD and support ICES in their mission to improve health and health care through data and discovery.

Conception d’une méthode pour déterminer la capacité d’un complexe manufacturier d’entretien, de réparation et de remise à niveau, avec application dans un contexte de turbines industrielles

La planification des opérations de maintenance est une tâche compliquée car elle est difficilement prévisible. La détermination des points bloquants dans la production permettra de mieux les éliminer et ainsi de réduire le temps de réparation des turbines. Pour cela, le stagiaire cherchera dans un premier temps à trouver le meilleur logiciel pour faire cette simulation puis il le mettra en place en collectant les informations nécessaires auprès du personnel responsable de la planification et des opérateurs. Une fois que la modélisation de l’état actuel sera correct, le stagiaire pourra mettre en place une optimisation de l’ordonnancement. Pour finir, il transmettra les connaissances qu’il aura acquises au personnel du service des opérations du partenaire.

Effects of low-dose radiation on immune parameters, antioxidant and metabolic signalling and implications in the development and progression of mammary cancer – Year two

Recent studies have called into question the Linear No Threshold (LNT) model of radiation protection, which predicts a linear increase in cancer risk with low-dose radiation exposure. However, current experimental evidence suggests that low-dose radiation (LDR, <0.1 Gy) elicits a non-linear response in biological systems and may result in beneficial effects, such as activation of anti-tumor immunity. Unfortunately, these studies lack detailed and mechanistic evidence to test the validity of the LNT model. As identified at a recent CANDU Owners Group (COG) workshop as well as in the COG Strategic R&D Program, there is a need to address Canadian public concerns surrounding exposures to low dose anthropogenic radiation. These concerns, as well as the validity of the LNT model, can only be addressed through comprehensive and mechanistic radiobiological studies. This project will provide a systematic and detailed investigation of the effects of LDR on immune system and implications in mammary cancer development and progression. Results of the project will provide the knowledge base and understanding of biological effects of low-dose radiation and inform regulators and policy makers so that more reliable radioprotection standards can be adopted.

Effects of low-dose radiation on immune parameters, antioxidant and metabolic signalling and implications in the development and progression of mammary cancer

Recent studies have called into question the Linear No Threshold (LNT) model of radiation protection, which predicts a linear increase in cancer risk with low-dose radiation exposure. However, current experimental evidence suggests that low-dose radiation (LDR, <0.1 Gy) elicits a non-linear response in biological systems and may result in beneficial effects, such as activation of anti-tumor immunity. Unfortunately, these studies lack detailed and mechanistic evidence to test the validity of the LNT model. As identified at a recent CANDU Owners Group (COG) workshop as well as in the COG Strategic R&D Program, there is a need to address Canadian public concerns surrounding exposures to low dose anthropogenic radiation. These concerns, as well as the validity of the LNT model, can only be addressed through comprehensive and mechanistic radiobiological studies. This project will provide a systematic and detailed investigation of the effects of LDR on immune system and implications in mammary cancer development and progression. Results of the project will provide the knowledge base and understanding of biological effects of low-dose radiation and inform regulators and policy makers so that more reliable radioprotection standards can be adopted.

Forced Air Ozone Reactor and Advanced Oxidative Process as an Alternative to Post-harvest Washing for Decontaminating Fresh Produce – Year two

The project will develop aqueous-free systems for decontaminating (i.e. inactivation of human pathogens and spoilage microbes) fresh produce that can be applied individually or sequentially. The first intervention is based on a forced-air ozone reactor that introduces the antimicrobial gas through the bed of produced at a controlled flow rate. The advantage of the method is large batches of produce can be treated and supports a higher log reductions of bacteria compared to when ozone is applied to storage rooms. The second intervention is based on Advanced Oxidative Process (AOP) that generates a cloud of antimicrobial radicles from the degradation of ozone and hydrogen peroxide that can decontaminate the surface, in addition to sub-surface. Each of the treatments will be modelled using Surface Response Methodology that will be used to optimize (log reduction of relevant pathogens and retention of sensor quality) each of the treatment parameters. The research will deliver aqueous-free decontamination methods as an alternative or supplement to post-harvest washing. In addition to being a more effective decontamination methods, the interventions will provide water savings and the potential to degrade pesticides. The participating partner will benefit from the expertise of the applicants knowledge of engineering, microbiology and food safety.