Uncover Spatial-Constraint Related Morphome Using Tissue-on-a-Chip Platform and Data-Driven Mathematical Modeling

使用芯片组织平台和数据驱动的数学建模揭示与空间约束相关的形态素

• 批准号: 10278972
• 负责人: Yu Huang
• 金额: $ 25.8万
• 依托单位: UTAH STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10278972
• 关键词: Address; Area; Behavior; Biological; Biological Process; Biological Sciences; Biophysics; Brain; Cell membrane; Complex; Data; Development; Epigenetic Process; Genetic; In Vitro; Machine Learning; Membrane; Modeling; Molecular; Morphology; Process; Shapes; Stimulus; System; Tissues; Work; biological systems; cell behavior; cranium; fascinate; in vivo; in vivo Model; interstitial; mathematical model; tool

PROJECT SUMMARY Cell behaviors and tissue developments often occur under spatial constraints (e.g., interstitial space, tissue lining, skull enclosure). The current in vitro systems are often open cultures, and thus miss the spatial constraints and other in vivo stimuli. The current in vivo models are often low throughput and hard-to-trace, therefore unable to unravel the complex interplay between intrinsic influences (e.g., genetics/epigenetics) and extrinsic ones (e.g., micro-environment). For example, cell membrane blebbing and brain folding are fundamental and impactful bio-behaviors under spatial constraints. Their biophysical and molecular mechanisms are not well understood. Lately, several experimental and theoretical tools have emerged to fascinate the modeling of complex bio-behaviors. This proposed study aims to parameterize morphological information, relate to the complex influences under spatial constraints, and unravel the mechanism of bio- behaviors in the two exemplified areas. It will be done through a morphome platform that integrates several experimental-theoretical tools (e.g., tissue-on-a-chip, data-driven modeling, machine-learning), which has been pre-defined by PI and Co-Is. We hope to 1) fill the compelling gaps in our understanding of membrane blebbing and brain folding process and 2) establish an effective strategy to uncover a broad range of basic biological processes.

项目摘要 细胞行为和组织发育通常在空间约束下发生（例如， 间隙空间、组织衬里、颅骨外壳）。目前的体外系统通常 开放培养，从而错过空间限制和其他体内刺激。的 目前的体内模型通常是低通量和难以追踪的，因此不能 解开内在影响之间的复杂相互作用（例如，遗传学/表观遗传学） 以及外在的（例如，微环境）。例如，细胞膜起泡和 脑折叠是在空间约束下的基本且有影响的生物行为。 它们的生物物理和分子机制还不清楚。最近，一些 实验和理论工具已经出现，吸引了复杂的建模， 生物行为 这项研究的目的是参数化形态信息，涉及到 复杂的影响下的空间限制，并解开机制的生物- 在两个示范区的行为。它将通过一个形态学平台完成 其集成了几种实验-理论工具（例如，芯片组织，数据驱动 建模，机器学习），这已经由PI和Co-Is预先定义。我们希望 1)填补了我们对膜起泡和大脑折叠的理解上的巨大空白 （2）制定有效的战略，以揭示广泛的基本 生物过程。