A comparative analysis of glycan variation and its effects on therapeutic protein function

There are many exciting therapeutic applications for proteins. Many diseases are caused by faulty enzymes, which can sometimes be replaced. Antibodies and antibody-like molecules are being developed to specifically target cancers and other diseases. However, in order to administer these products, they must be made in a way that has minimal effect on the patient’s immune system. To make them viable commercially, they also have to be made in a robust, cost-effective process.

Advanced differential mobility mass spectrometry with electron capture dissociation for the characterization of therapeutic proteins - Year two

Many new pharmaceuticals are based on large biomolecules like proteins. Even small differences in the protein structure can cause significant changes in the efficacy and safety of these drugs. Furthermore, these large molecules are difficult to characterize without advanced instrumentation and methods. Current technologies still struggle with robustness and reproducibility. This study aims to introduce new technology to improve the reliability of protein pharmaceutical characterization.

Development of new classes of bio-relevant linkers for PROTACs and other conjugates using new technologies - Year two

Les PROTACs sont de nouvelles molécules thérapeutiques ayant pour but de soigner certaines maladies grave comme les cancers. Ces composés sont des molécules linéaires constitués de trois composants principaux : une extrémité permettant de repérer la cible, une autre extrémité permettant de causer la dégradation de cette cible, et enfin un linker reliant les deux. Cette dernière partie est la moins étudié, bien qu’il ait récemment été prouvé qu’elle joue grandement sur les propriétés de la molécule finale.

Investigating the Paradoxical Adoption of Blockchain in Healthcare Data Sharing: The Patterns, Consequences and Mediating Mechanisms of Challenging yet Succumbing to Incumbents

In this Mitacs project, we examine how nascent technology advocators can successfully implement the technology in highly institutionalized settings. Using the implementation of Blockchain in healthcare data sharing as an example, we compare and contrast the implementation strategies of 6-8 start-ups or divisions of established companies, and examine how the different types of implementation strategies lead to different implementation outcomes. Based on this research, BI will learn about the key advocators of Blockchain for healthcare data sharing, their strategies and performance.

Full characterization of Drug-Drug interactions using deep learning methods

Better understanding Drug-Drug interactions (DDIs) is crucial for planning therapies and drugs co-administration. While, considerable efforts are spent in labor-intensive in vivo experiments and time-consuming clinical trials, understanding the pharmacological implications and adverse side-effects for some drug combinations is challenging. The majority of interactions remains undetected until therapies are prescribed to patients. We propose to use computational tools for predicting interactions in order to reduce experimental costs and improve safety.

In Vitro Screening and Validation of Phyto-Cannabinoids in Glaucoma

Glaucoma is the second leading cause of blindness in the world, mainly induced by increased pressure in the eye. Marijuana has been shown to reduce such pressure, thus benefit glaucoma patients. In this project, we test several components from marijuana extracts that are unlikely to cause psychoactive symptoms, for their therapeutic effects on glaucoma. This project is likely to be the solid base of a future drug that could help lots of glaucoma patients and meet the need of the market.

Splicing alterations: from pathogenic variant discovery to next generation therapeutics development

Many human genetic diseases are associated with defects in post-transcriptional gene regulation and alternative splicing. Despite rapid technological advancements, successful diagnostic rates for rare genetic disorders are still low and clinical interventions and treatments unavailable for most patients. This project aims to address this challenge by developing novel antisense RNA therapies based on the splice-switching oligonucleotide (SSO) technology. SSOs allow correcting aberrant transcript splicing by targeting disease mutations at the transcript level.

Nanoparticle-encapsulated Cannabinoid and Temozolomide Combination Therapy for the Treatment of Glioblastoma Multiforme

Glioblastoma multiforme (GBM) (the deadliest form of brain cancer) is associated with poor survival rates (approximately 12-15 months from the time of diagnosis). This is due to the fact that most cases of GBM are resistant to current standards of care. As a result, novel effective treatment options are highly desirable. It has recently been shown that the combination of cannabinoids (such as THC or CBD) with the standard of care chemotherapy agent, temozolomide, demonstrates promise in the treatment of animal models of GBM.

Exploring various approaches for investigating the mechanism of native diphtheriae toxin production by a C. diphtheriae strain: From –omics to nutritional to process approaches

Diphtheria is still a disease causing significant morbidity and mortality in people worldwide that did not received vaccination or suffer from incomplete immunization. The disease is due to a powerful toxin produced by the pathogenic bacterium Corynebacterium diphtheria. A good vaccine already exists but its production is rather complex and involves several steps: cultivation of the microorganism, extraction, concentration and inactivation of the toxin followed by extensive purification of the inactivated toxin (toxoid).

VAL-083 combination therapies in chemo-resistant pediatric CNS cancers

More children die from brain cancer than from any other disease in the western world. Many anti-cancer drugs are unable to cross the blood-brain barrier to reach the tumor and certain genetic mutations in the tumor cells increase resistance to chemotherapeutics. The novel chemotherapeutic drug VAL-083 readily crosses the blood-brain barrier and accumulates in brain tumor tissues and has documented activity against pediatric brain tumors in historical clinical trials.

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