Epithelial Cell Migration: Model selection for mechanistic model development

项目摘要 细胞的集体迁移是多细胞生物的一个重要生物学过程。 在伤口愈合过程中，上皮片集体迁移以闭合差距是一种极好的方法。 这一现象的例证。不适当的迁移运动可导致伤口受损 愈合，如在慢性伤口和糖尿病足溃疡中所见。虽然大量的研究已经 致力于它的研究，我们仍然缺乏对是什么驱使细胞群 由于无法治愈的慢性伤口仍然没有治愈性疗法，因此需要协调一致地采取行动。博尔茨， Liu和Dukic团队正在共同开发一种基于模型选择的方法， 揭示了控制集体细胞迁移的驱动机制。因此，长期的数学 我们的目标是开发和应用一个计算效率高，严格适定的模型选择 用微分方程模拟时空生物现象的方法。 为此，我们将采用一种协同的实验、数学和统计方法 开发可行的候选模型，设计并进行验证实验，并选择 最好的模型来推断主导的驱动机制。虽然我们在这方面取得了很大的进展， 开发数学框架来模拟各种细胞迁移行为，这是一个瓶颈 释放我们新方法的潜力的原因是细胞迁移测定的有限通量 这是由于手动实验设置繁琐且耗时。此外， 手工操作是容易出错的，并且在实验之间引起可避免的变化。ASSIST PLUS Integra Biosciences生产的用于细胞培养研究的半自动液体处理 和药物治疗。购买这个机器人系统将使我们能够进行许多 更有力地进行实验，加速我们的研究项目。

Project Summary The collective migration of cells is a central biological process for multicellular organisms. Collective migration of epithelial sheets to close the gap during wound healing is an excellent illustration of this phenomenon. Inappropriate migratory movements can result in impaired wound healing, as seen in chronic wounds and diabetic foot ulcers. While substantial research has been devoted to its study, we still lack a foundational understanding of what drives groups of cells to move coherently as curative therapies are still not available for unhealable chronic wounds. Bortz, Liu, and Dukic groups are working together to develop a model selection-based approach to reveal driving mechanisms that control collective cell migration. Thus the long-term mathematical goal is to develop and apply a computationally efficient and rigorously well-posed model selection methodology for spatio-temporal biological phenomena modeled by differential equations. Toward this end, we will pursue a synergistic experimental, mathematical, and statistical approach to develop feasible candidate models, design and carry out validating experiments, and select the best models to infer the dominant driving mechanisms. While we made a lot of progress in developing mathematical frameworks for modeling various cell migratory behaviors, a bottleneck for unlocking the potentials of our new approach is the limited throughput of cell migration assays due to the manual experiment setup, which is tedious and time-consuming. Moreover, pipetting by hand is error-prone and induces avoidable variability between experiments. ASSIST PLUS from Integra Biosciences is designed for semi-automated liquid handling for cell culture studies and drug treatments. Acquisition of this robotic system will enable us to conduct numerous experiments in a more robustly and accelerate our research project.