An automated manufacturing and high speed imaging platform for identifying functional perturbations in engineered tissues

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The explosion of “omic” data from various cell and tissue samples has created a vast collection of biological information from which we can understand the complex networks that control these living materials at a molecular level. Decoding these massive and noisy datasets to understand how molecular interactions instruct cell and tissue function however, remains a major challenge in modern biology. Approaches to efficiently connect molecular perturbations to complex cell functions would transform our capacity to explore these massive datasets and decode the underlying biological control networks. Towards this endeavour, we request support to explore three complex cell functions with genomics experts in the context of next-generation engineered tissues: 1) cellular migration, 2) stem cell activation, expansion, differentiation, and self-renewal after injury and 3) cellular competition. Our team has the expertise and records of collaboration required to achieve success in this multi-disciplinary project rooted at the intersection of genomics, engineering, chemistry and cell biology. Critical to our success is the ability to reproducibly manufacture our tissue models and perturb specific signaling pathways to connect genotype to phenotype. To achieve this, we request three integrated instruments necessary for our success: 1) a digital compound dispenser capable of preparing compound libraries for phenotypic screens to relate known pathways to cell function; 2) a robotic pipetting system capable of automating the manufacture of engineered tissue models to ensure reproducibility; 3) a replacement confocal microscope laser system for live cell imaging of cell behaviour to identify perturbations that produce functional changes. This equipment will be widely accessible within our labs and across campus and industry. Undergraduates, graduate students, and post-doctoral fellows will be trained on this cutting- edge equipment, preparing them for advanced research careers in industry, academia and government, ultimately benefitting Canada and the knowledge-based economy.