CAREER: Mechanically-Induced Dysfunction: From the Cell to the Organ

9702088马古利斯这项综合研究和教育计划的主要目标是制定研究和教育方案，跨越细胞和器官水平之间的跨学科鸿沟，重点是所施加的物理力量对功能和结构的影响。这项研究计划是朝着了解活体肺上皮衬里变形并确定这些变形对肺的不利影响的长期目标迈出的第一步。气压伤，或过度膨胀的肺泡破裂后肺泡外空气的存在，是持续的大潮气量机械通气的结果。总的假设是，肺泡上皮衬里在机械通气过程中容易受到大的静态和动态变形的损伤。该研究计划利用体外细胞培养研究、数学模型和体内实验研究，将机械变形与肺上皮表面活性物质产生和屏障特性的破坏联系起来。职业发展计划的教育部分的长期目标是创建将基础工程理论与生物医学应用相结合的生物工程研究生课程。将开发三门课程：1)心胸生理学综合课程，汇集分子、细胞和器官层面的基本知识和最新研究成果，将细胞和分子机制与宏观功能反应联系起来；2)粘弹性组织行为和大应变测量技术和分析课程；以及3)实验设计和分析以及科学责任。综合研究和教育事业发展计划的双重使命是满足日益增长的跨学科研究和教育机会的需求，以回答基本的科学问题。***

9702088 Margulies The primary objective of this integrated research and educational plan is to develop research and educational programs that span the interdisciplinary chasm between the level of the cell and the organ, with an emphasis on the effects of applied physical forces on function and structure. The research plan is a first step towards the long-term goals of understanding the deformations of the epithelial lining of the lung in vivo, and determining the effects of these deformations on the lung's adverse effects. Barotrauma, or the presence of extra-alveolar air after rupture of over-distended alveoli, is the consequence of a sustained mechanical ventilation with large tidal volumes. The overall hypothesis is that the alveolar epithelial lining of the lung is vulnerable to injury from large static and dynamic deformations during mechanical ventilation. The research plan relates mechanical deformation to disruption of the epithelial surfactant-producing and barrier properties of the lung using in vitro cell culture studies, mathematical models, and in vivo experimental studies. The long-term goal of the educational component of the career development plan is to create Bioengineering graduate courses that integrate fundamental engineering theories with biomedical applications. Three courses will be developed: 1) a course in integrated cardiothoracic physiology that brings together basic knowledge and recent research findings from the molecular, cellular and organ levels to correlate cellular and molecular mechanisms with macroscopic functional responses; 2) a course in viscoelastic tissue behavior and large strain measurement techniques and analysis; and 3) experimental design and analysis, and scientific responsibility. The dual mission of the integrated research and educational career development plan is to meet the growing need for research and educational opportunities that cut across disciplines to answer fundamental scientific questions. ***