Virtual Lung Project: Integrated Modeling of Epithelial

虚拟肺项目：上皮细胞综合建模

• 批准号: 7125868
• 负责人: RICHARD SUPERFINE
• 金额: $ 72.8万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125868
• 关键词: biophysics; computational biology; computer simulation; confocal scanning microscopy; cystic fibrosis; human tissue; ion transport; lung; mathematical model; mucins; mucus; nonblood rheology; nucleosides; nucleotides; respiratory epithelium; shear stress; tissue /cell culture

DESCRIPTION (provided by applicant): The flow of liquid on mucosal surfaces is ubiquitous in human physiology. The failure of cilia and airflow induced liquid flow in the lungs (mucus clearance), as in Cystic Fibrosis, primary cilia dyskinesis, and environmentally damaged lungs, leads to severe health problems as the lung tissue will be destroyed by infections that cannot be cleared. Significant progress has been made in recent years in identifying the key genetic mutation responsible for Cystic Fibrosis, studying the hydrodynamics and biochemistry of airway mucus and beginning to develop effective treatments. In parallel, theory and simulation have begun to tackle issues such as the basis for force production in biological molecules, the rheology of biological fluids and hydrodynamics of viscous, complex flows. We stand at a critical time when an understanding of biological systems assembled into a unified simulation is essential for making breakthroughs in the science of microbiological hydrodynamics. The approach of this project is to develop sophisticated physics-based models of polymer dynamics and viscoelastic hydrodynamics in close coordination with experiments in human bronchial epithelial cell cultures. Through a combination of established and advanced techniques, the project will develop an integrated view of the biophysics of the mucus clearance system from the molecular scale seen by signaling molecules and viruses, up to the millimeter scales that control flow. By combining a team of researchers from Applied Mathematics, Chemistry, Physics and Astronomy, Biochemistry and Biophysics, and the Cystic Fibrosis Center, the long term goal is to develop an integrated computational model that will be able to predict and evaluate truly effective therapeutic strategies. The challenge in developing this comprehensive approach is to proceed through a series of research goals that accomplish short range impact.

描述（由申请人提供）：液体在粘膜表面的流动在人体生理学中是普遍存在的。纤毛和气流的衰竭导致肺部液体流动（粘液清除），如囊性纤维化、原发性纤毛运动障碍和环境受损的肺部，会导致严重的健康问题，因为肺部组织会被无法清除的感染所破坏。近年来，在确定导致囊性纤维化的关键基因突变、研究气道粘液的流体动力学和生物化学以及开始开发有效的治疗方法方面取得了重大进展。与此同时，理论和模拟已经开始解决诸如生物分子中产生力的基础、生物流体的流变学和粘性复杂流动的流体动力学等问题。我们正处于一个关键时刻，对生物系统的理解组装成一个统一的模拟对于在微生物流体动力学科学上取得突破至关重要。本项目的方法是开发复杂的基于物理的聚合物动力学和粘弹性流体动力学模型，并与人类支气管上皮细胞培养实验密切配合。通过现有技术和先进技术的结合，该项目将从信号分子和病毒所看到的分子尺度，一直到控制流量的毫米尺度，对粘液清除系统的生物物理学进行综合研究。通过联合来自应用数学、化学、物理和天文学、生物化学和生物物理学以及囊性纤维化中心的研究人员，长期目标是开发一个综合计算模型，能够预测和评估真正有效的治疗策略。发展这种综合方法的挑战是通过一系列实现短期影响的研究目标。