CAREER:Engineering Functional Tissue Assembly and Remodeling Through Developmental Biology

点击翻译按钮获取中文摘要

Tissue assembly and remodeling occurs at significantly faster rates during embryogenesis than in adulthood, but these mechanisms are poorly understood. Efficient strategies to control tissue adaptation and remodeling, as well as accelerate the construction of cardiovascular tissue replacements, can be gained by harnessing "natural engineering" paradigms that prescribe cardiovascular development and maturation. This proposal will uncover these mechanisms for heart valves, a critically important cardiovascular soft tissue. The guiding hypothesis is that heart valve tissue assembly and remodeling is controlled by a mechanically sensitive genetic signaling network that is active during valvulogenesis and reactivated in aged valves.This proposal addresses a fundamental gap in our understanding of tissue assembly and remodeling processes with unique experimental and computational tools. These studies will provide first mechanistic insights integrating organ, tissue, cell, and molecular length scales that will transform engineering strategies to control valvular remodeling at any stage in the lifecycle. Implementation of a novel living embryo culture system will enhance inquiry based learning curricula. Assimilation of developmental biology and engineering at the graduate level will give specialized students much needed breadth. Unique experimental tools suitable for mouse tissues will enable quantitative mechanistic understanding of important functional consequences of sublethal genetic mutations. The visible living embryo system implemented in this proposal can be used as a centerpiece to communicate many basic phenomena to the general public as well as the scientific community. This will augment awareness and appreciation for the advancement of science.