Projets novateurs réalisés

Addressing Cardiac Conductive Disturbances Following TAVI Procedures: Optimizing Post-Procedure Care

Cardiac conduction disturbances (CDs) are a prevalent complication of transcatheter aortic valve implantation (TAVI) procedures, which are performed by interventional cardiologists to treat heavily calcified aortic valves. CDs may emerge during or after TAVI, and are typically caused by mechanical injury to the heart’s conduction system, which can be highly challenging to prevent during the procedure. Post-TAVI, patients may either receive a permanent or temporary pacemaker depending on their level of risk. Patients at high risk may receive a permanent pacemaker (PPM), however studies have shown that PPM dependency rates 30 days after TAVI range from 35% to 44%, highlighting a substantial subset of patients who may have received an unnecessary PPM. Conversely, patients with uncertain risk may be given a temporary pacemaker for further monitoring in the ICU, leading to an extended hospital stay and placing an additional financial burden on the healthcare system. Furthermore, around 2% of patients develop late-onset CDs after their in-hospital post-operative monitoring, yielding to future rehospitalization. To address this, we are developing a new form of pacing that is both temporary and ambulatory, allowing patients to safely return to their daily activities without the need for extended hospital stays and reducing unnecessary PPM implantations.

Biophysical and Structural Characterization of Peptide Macrocycle-based Huntingtin Degraders

Huntington’s Disease (HD) is a debilitating neurodegenerative disease marked by progressive loss of motor control and cognitive function. Presently, there are no disease-modifying therapies. A potential avenue for slowing or stopping HD progression is to target huntingtin (HTT), or polyglutamine-expanded mutant HTT (mHTT), for degradation using proteasome targeting chimera (PROTAC) technology. A PROTAC will bring HTT and an E3 ligase into close proximity so that the E3 ligase can ubiquitinate HTT, serving as a degradation signal in the cell.
An ongoing collaboration between the labs of Rachel Harding and Hiroaki Suga has yielded a collection of HTT-targeting macrocyclic peptides (MPs). MPs offer the combined benefits of antibody-like specificity and small molecule-like cell permeability and stability. On the other hand, conveniently, the Structural Genomics Consortium has recently discovered a micromolar affinity ligand for TRIM7, an E3 ligase expressed in the brain.
To develop HTT-TRIM7 PROTACs, they will first be modeled in silico for optimal linker length and composition and then synthesized in collaboration with SGC. Next, PROTAC functionality and specificity will be validated by monitoring degradation of HTT in the cell. Finally, the HTT-PROTAC-TRIM7 complex will be visualized and corroborated using Cryogenic Electron Microscopy (Cryo-EM) and Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS).
Consistent with Dr. Harding’s and the SGC’s commitment to open science, all work will be shared openly and contribute to the knowledge base of precompetitive, preclinical science. Together, we will take steps toward HD-modifying therapeutic interventions.

Characterization of TEC kinase small molecule compounds

Peripheral T-cell lymphoma (PTCL) is a type of blood cancer with poor treatment outcomes, as patients often relapse or do not respond to available therapies. A key factor driving the growth of cancerous T cells in PTCL is a protein called ITK, which helps these cells survive by activating biological pathways that boost cell growth and survival. Our project focuses on developing new treatments by targeting a specific part of the ITK protein called the PHTH domain, which is essential for ITK to function. Current drugs that target ITK usually aim at the protein’s active site, but they often cause unwanted side effects or lose effectiveness over time. Instead, we’re exploring a different approach by finding molecules that can bind to the PHTH domain, preventing ITK from working and stopping the growth of cancer cells.

Using advanced screening technology, we will identify potential molecules that interfere with ITK at the PHTH domain. We will then test these molecules to understand how they work and evaluate their potential as treatments in PTCL models. Additionally, we will investigate whether combining these molecules with other drugs that trigger cell death (called BH3-mimetics) could make the treatment more effective. This research could lead to new, more precise treatments for PTCL, addressing a significant need for better therapies.

Metering and Aggregation, and, Electrification of Buildings Part 1

With the pressing need to reduce energy from carbon emitting sources, electrification of buildings is a crucial step forward. Electrification requires identifying activities and equipment that use energy received from carbon emitting sources and transitioning them to electric alternatives. The proposed research focuses on developing methods and strategies to overcome challenges associated with building electrification and load prediction models.
This project will benefit the partner organization by identifying opportunities for energy costs savings, supporting the transition to cleaner, more sustainable energy sources.

Bond strength and development length of GFRP hooked bars

Infrastructure is facing significant environmental effects and climate change effects, compound by service conditions, which lead to rapid deterioration of bridges or marine structures for example. Corrosion of steel reinforcement in concrete structures is perhaps the main concern. Fiberglass reinforcing bars emerged as a promising alternative to steel bars and offer far better durability due to corrosion resistance. However, focus has been primarily on straight bars in long structures. There are many conditions where the length of the structural members is limited and a straight bar might slip prematurely from concrete. In this case a bent bar (or a hooked bar) is necessary. Very limited studies available on bent bars, perhaps only two, more than 30 years ago. This program will address modern fiberglass bent bars and provide critical test data that will enable updating a rather outdated design equation in design codes.

Point Cloud Data Fusion for High-Precision Inspection of Aerospace Parts

This project aims to develop an innovative method to enhance the accuracy and efficiency of inspecting aerospace parts, such as aero-engine blades. These components often have intricate shapes, making precise inspection a significant challenge. To overcome this, the project combines data from two measurement systems: one that captures detailed 3D scans and another that provides sparse but highly accurate reference points. By intelligently merging these datasets using adaptive sampling and advanced algorithms, we create highly accurate digital models of the parts. The research will enable faster and more precise part inspection, reducing production bottlenecks and costs. By advancing inspection techniques, this project will directly support the competitiveness of the Canadian aerospace manufacturing industry, helping it maintain a leadership position in producing high-quality, reliable components for global markets.

Smart Aircraft Wings Constructed via Reconfigurable Metamaterials

Traditional airplane wings operate via an intricate system, including rigid control surfaces, motors, cables, and
hydraulics. Wings can deform, e.g., slide and tilt rigid control surfaces, to control airflow passing over them.
Though with high reliability, traditional wings are heavy. A lighter alternative is smart wings constructed via
morphable materials, such as shape memory alloys/polymers or morphable meta-materials. Assembled from
morphable meta-materials, smart wings can change shapes to control the plane’s flight and significantly boost
aircraft production, flight, and maintenance efficiency. However, associated research on the morphing actuating
of meta-materials has lagged behind, holding meta-materials from wider industrial applications. This MITACS
GRA project will develop smart aircraft wings constructed via reconfigurable smart meta-materials.

Adapting the Cool Farm Tool for Achieving Net-Zero Emissions in Nova Scotia’s Agriculture

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Barley research benefit project

The Canadian Barley Research Coalition (CBRC) is a national not-for-profit organization that funds long-term research projects in the barley sector. The CBRC was awarded $10.2 million to direct towards barley research between 2018 and 2023. This research project will examine the benefits of this research funding to the barley sector in Canada. The project will be completed by an MSc student, who will use the research as the basis for their MSc thesis.

Développement d’outils d’analyse de faisabilité de portefeuilles d’évènements dans un centre de congrès

Le Palais des Congrès de Montréal est une institution publique à vocation commerciale qui génère d’importantes retombées économiques pour le Québec. Un défi majeur pour cette institution est la planification annuelle de plus de 350 événements de nature et d’envergure variées, tout en respectant diverses contraintes opérationnelles et commerciales pour atteindre les objectifs fixés par le ministère du Tourisme. Pour relever ce défi, nous proposons d’analyser et d’améliorer le processus de suivi des temps d’opérations lors de la mise en place des événements, ainsi que de proposer un outil capable d’assigner des salles aux événements en fonction des contraintes propres au Palais des Congrès. Ce projet de recherche s’appuiera sur les travaux antérieurs portant sur la gestion de portefeuilles d’événements pour les centres de congrès, ainsi que sur les modèles de planification et d’assignation de ressources pour les portefeuilles de projets. De plus, cette recherche valorisera les données historiques du Palais des Congrès de Montréal afin d’analyser les variables influençant la faisabilité d’un portefeuille d’événements.

Fraud Detection in Financial Graphs

A significant amount of fraudulent activity tends to go unreported in reality, one of the major focuses for our team recently has been to develop robust GNNs that can perform anomaly detection on noisily labeled graphs. Noisily labeled anomalous data can reduce the model performance as it learns incorrect patterns during training, cause the model to overfit the noise in the labels as opposed to the underlying true anomalies, and can harm the message-passing mechanism of the GNNs.
Having a GNN based model that is robust to noisy labels can provide us with a significant uplift over the current production models. In research, there is limited work already done in this domain using GNNs. However, applying these methods to Mastercard’s data in a way that transfers well is a challenging task due to:
a) Heavy Class Imbalance b) Inductive – Model should perform well for out-of-distribution test set c) Scalability – the model should learn from over one billion noisily
labeled data d) Nature of Graph – Transaction graph is significantly different from other open source graphs used in existing research

Greenhouse gas emissions and Sustained Flux Global Warming/Cooling Potential of two constructed wetlands from south-central Ontario

Constructed wetlands are multifunctional natural-like systems created for wastewater treatment, biomass production, water storage, flood retention, and wildlife habitat. Constructed wetlands where water-loving plants grow can also absorb carbon dioxide from the atmosphere and thus potentially contribute to offsetting greenhouse gas emissions produced by human activities. However, like all wetlands, constructed wetlands also produce greenhouse gases themselves, such as methane and nitrous oxide, two powerful gases that contribute to global warming. In this project, we partnered with Lake Simcoe Region Conservation Authority, an organisation working with local communities to protect and restore the Lake Simcoe watershed by leading research, policy, and action since 1951, to determine if constructed wetlands in their jurisdiction can offer climate benefits, that is, if they can remove more carbon dioxide from the atmosphere than the equivalent they emit as greenhouse gases. Through this project we aim to provide our partner with management recommendation for constructed wetlands that maximizes their climate benefits while, at the same time, provide various co-benefits, such as wildlife habitat and landscape beautification. In addition, we will train a Masters student to be an expert in this field.