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体的中心生物学过程。 在伤口愈合过程中，上皮片的集体迁移以弥合缝隙是一种极好的方法 这一现象的例证。不适当的迁徙运动可导致创面受损 愈合，如慢性伤口和糖尿病足部溃疡。虽然大量的研究已经在 致力于它的研究，我们仍然缺乏对是什么驱使细胞组 行动一致，因为无法治愈的慢性伤口仍然没有治愈的治疗方法。波尔茨 刘和Dukic团队正在合作开发一种基于模型选择的方法来 揭示控制集体细胞迁移的驱动机制。因此，长期的数学问题 目标是开发和应用一种计算高效且严格适定的模型选择 用微分方程式模拟时空生物现象的方法学。 为此，我们将采取协同实验、数学和统计方法 开发可行的候选模型，设计并进行验证性实验，并选择 推断主导驱动机制的最佳模型。虽然我们在以下方面取得了很大进展 开发数学框架来模拟各种细胞迁移行为，这是一个瓶颈 我们新方法的潜力在于有限的细胞迁移分析吞吐量 由于手动实验设置繁琐且耗时。此外，移液器 手工操作容易出错，并在实验之间引起可避免的变异性。助攻加 是为细胞培养研究的半自动液体处理设计的 和药物治疗。收购这个机器人系统将使我们能够进行无数次 在一个更加稳健的实验中，加速了我们的研究项目。

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.