CAREER: Controlling Soluble Morphogen Gradients in Biomaterials

自然界中的发育和再生过程通常依赖于影响细胞活动的蛋白质浓度梯度。当干细胞形成新的组织和组织界面时，这些蛋白质的空间分布会影响干细胞的表型。在自然系统中，局部的蛋白质分泌和随后通过细胞外基质(ECM)的运输往往决定了所产生的浓度梯度的性质，进而决定了生物效应。这个项目的方法将是在合成材料中以受控的方式模拟这一自然机制，以便将受控的可溶形态原梯度输送到细胞。该项目的目的是：1)确定控制合成水凝胶中可溶蛋白质梯度的参数；2)使用水凝胶基质研究形态梯度对成体干细胞表型的影响，最终目标是使用这些系统来设计组织界面。该项目的跨学科方法将与教育活动交织在一起，在研究生培训、本科教育和社区推广中整合生物、生物工程和科学政策。该教育计划将制定和评估：1)跨学科研究生实习计划，使学生接触到生物学、生物工程和公共政策之间的联系；2)支持跨学科研究生研究人员与科学、技术、工程和数学(STEM)学科中不具代表性的少数群体本科生之间的合作；以及3)促进生物、物理和社会科学之间互动的跨学科教育和拓展经验。

0745563MurphyAbstractDevelopment and regeneration processes in nature often rely on protein concentration gradients that influence cell activity. The spatial distribution of these proteins, often termed ?morphogens?, influence the phenotype of stem cells as they form new tissues and tissue interfaces. In natural systems, localized protein secretion and subsequent transport through the extracellular matrix(ECM) often dictate the properties of the resulting concentration gradient and, in turn, the biological effect. The approach of this project will be to mimic this natural mechanism in a controlled manner in synthetic materials in order to deliver controlled soluble morphogen gradients to cells. This project is designed to: 1) determine the parameters that control soluble protein gradients in synthetic hydrogels; and 2) use hydrogel matrices to study the influence of morphogen gradients on adult stem cell phenotype, with the ultimate goal of using these systems to engineer tissue interfaces. The interdisciplinary approach of this project will be intertwined with educational activities that integrate biology, bioengineering, and science policy in graduate student training, undergraduate education, and community outreach. The education plan will develop and assess: 1) an interdisciplinary graduate internship program that exposes students to the interface between biology, bioengineering, and public policy; 2) a program that supports collaboration between interdisciplinary graduate researchers and undergraduates from underrepresented minority groups in the Science, Technology, Engineering and Mathematics (STEM) disciplines; and 3) interdisciplinary education and outreach experiences that catalyze interactions between biological, physical, and social sciences.