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

用于识别工程组织中功能扰动的自动化制造和高速成像平台

• 批准号: RTI-2021-00523
• 负责人: McGuigan, Alison
• 金额: $ 10.93万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=718842
• 关键词: automated; manufacturing; speed; imaging; platform

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.

来自各种细胞和组织样本的“基因组”数据的爆炸式增长创造了大量的生物信息，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，解码这些海量和噪声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的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，我们请求支持基因组学专家在下一代工程组织的背景下探索三种复杂的细胞功能：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根植于基因组学、工程学、化学和细胞生物学交叉点的多学科项目中取得成功所需的专业知识和合作记录。 我们成功的关键是能够重复制造我们的组织模型，并干扰特定的信号通路将基因型与表型联系起来。为了实现这一目标，我们需要成功所必需的三种集成仪器：1)数字化合物分配器，能够为表型筛选准备化合物文库，以将已知途径与细胞功能联系起来；2)机器人移液系统，能够自动制造工程组织模型，以确保重复性；3)替换的共焦显微镜激光系统，用于对细胞行为进行实时细胞成像，以确定导致功能变化的扰动。 该设备将在我们的实验室内以及整个校园和行业中广泛使用。本科生、研究生和博士后研究员将接受这种尖端设备的培训，为他们在工业、学术界和政府的高级研究生涯做好准备，最终使加拿大和知识经济受益。