In the face of the rapidly increasing global threat of antimicrobial resistance (AMR), we urgently need new technologies to improve AMR surveillance, diagnosis of infections, management of outbreaks, and antimicrobial stewardship. Antifungal resistant Candida species, like Candida auris, are increasingly included on urgent AMR threat lists because they can be difficult to treat and can cause deadly hospital outbreaks. A current challenge in tackling AMR is that antimicrobial susceptibility testing may only be performed in centralized reference laboratories, incurring delays in information critical for matching patients to best treatments.

CRISPR-based diagnostics enable high sensitivity and specificity detection of genetic biomarkers. This project leverages clinical and engineering expertise to develop rapid CRISPR diagnostic assays to detect C. auris, other Candida, and key genetic mutations known to facilitate antifungal resistance. The assay will be optimized for use in a clinical microbiology laboratory and validated with a variety of clinical samples, drawing on collaborations across the Toronto healthcare system. It will also demonstrate the use of the assay for rapid assessment of environmental surveillance samples to help guide decision making by infection control teams in hospitals. This data unlocks the potential to implement the assay as a diagnostic and surveillance test at Shared Hospital Laboratory as well as laying the groundwork for future research into broader implementation of AMR and infectious disease diagnostics. It will also equip students with multidisciplinary research, problem solving, and communication skills, training them to be our future leaders and innovators in the Canadian and global fight against AMR.

Serious respiratory viral infections including SARS-CoV-2, RSV and influenza viruses can result in acute respiratory disease syndrome (ARDS), a condition caused by uncontrolled recruitment of immune cells that release toxic mediators and proteins that ultimately damages the lungs, specifically the alveolar epithelium, the region of the lung involved in gas exchange. Drug development has traditionally relied on the use of transformed cell lines that do not represent the cells found in the lungs, and animal models that often do not translate to human outcomes, especially when infections and disease manifestations in humans are mirrored in animals. We propose to develop a novel biomimetic human lung tissue that better models the native tissue that will allow us to study host-pathogen interactions for viruses like RSV. To do this, we will leverage our existing organ-on-a-chip platform called E-FLOAT to create an alveolus-on-a-chip model from human induced pluripotent stem cells, a renewable cell source with the capability of generating any cell type in the lungs, including the cells that make up the alveolar epithelium. Our goal is to create a tissue model that is critically needed to study respiratory infections and enable rapid development of potential therapeutics for pandemic level viruses.