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

来自各种细胞和组织样本的“组学”数据的爆炸式增长创造了一个巨大的生物信息集合，从中我们可以了解在分子水平上控制这些生物材料的复杂网络。然而，解码这些庞大而嘈杂的数据集，以了解分子相互作用如何指导细胞和组织功能，仍然是现代生物学的主要挑战。有效地将分子扰动与复杂细胞功能联系起来的方法将改变我们探索这些海量数据集和解码潜在生物控制网络的能力。为此，我们请求基因组学专家在下一代工程组织的背景下支持研究三个复杂的细胞功能：1)细胞迁移；2)干细胞激活、扩增、分化和损伤后的自我更新；3)细胞竞争。我们的团队拥有在这个多学科项目中取得成功所需的专业知识和合作记录，该项目植根于基因组学、工程学、化学和细胞生物学的交叉领域。

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.