The Virtual Lung Project: Integrated Modeling of Epithelial Fluid Flows

虚拟肺项目：上皮液流的集成建模

基本信息

批准号：
7907622
负责人：
RICHARD SUPERFINE
金额：
$ 69.07万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7907622
关键词：
Address Astronomy Biochemical Biochemistry Biological Biophysics Cell Culture Techniques Chemistry Cilia Complex Computer Simulation Cystic Fibrosis Development Environment Epithelial Epithelial Cells Exclusion Failure Feedback Friction Gene Mutation Glycoproteins Goals Guns Health Human Infection Ions Liquid substance Lubrication Lung Mathematics Measures Membrane Modeling Molecular Molecular Models Mucins Mucous body substance Nucleosides Nucleotides Physics Physiology Polymers Principal Investigator Production Property Proteins Regulation Research Research Personnel Rheology Science Series Signaling Molecule Stress Structure Structure of parenchyma of lung Surface System Techniques Therapeutic Time Virus Water airway surface liquid base biological systems cellular microvillus crosslink effective therapy extracellular fluid flow millimeter molecular modeling molecular scale particle programs research study response sensor shear stress simulation theories therapy design virtual viscoelasticity

项目摘要

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）：粘膜表面上的液体流动在人体生理学中是普遍存在的。纤毛和气流的失败导致肺部液体流动（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，因为肺组织将被无法清除的感染破坏。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力产生的基础、生物流体的流变学以及粘性复杂流的流体动力学等问题。我们正处于一个关键时刻，理解组装成统一模拟的生物系统对于微生物流体动力学科学的突破至关重要。该项目的方法是与人类支气管上皮细胞培养实验密切配合，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。通过结合现有的和先进的技术，该项目将开发粘液清除系统生物物理学的综合视图，从信号分子和病毒的分子尺度到控制流动的毫米尺度。通过结合来自应用数学、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团队，长期目标是开发一个集成的计算模型，能够预测和评估真正有效的治疗策略。开发这种综合方法的挑战是实现一系列实现短期影响的研究目标。