CAREER: Using Functionalized Protein-based Materials to Control and Pattern Cell Behavior

这项由材料研究部的生物材料项目授予德克萨斯A&A&M健康科学中心的职业奖项是开发在三维支架中结合和构图活性结构蛋白质的方法，从而极大地扩展了在细胞生物学和组织工程研究中操纵细胞行为的能力。制造材料或使材料功能化的常见方法可能会损害敏感分子。细胞因子是控制生长、迁移、凋亡和分化的蛋白质，特别容易受到攻击。有了这一奖项，功能化材料将使用果蝇蛋白超双胸(UBX)一步制备出来。Ubx在温和的缓冲液中快速自组装，使基因上与Ubx融合的细胞因子保持活性。细胞因子-Ubx融合材料将用于指导和塑造三维支架内的血管生成。蛋白质的性质将被定义为允许掺入，对嵌入材料中的细胞因子相对于可溶性单体的活性进行基准测试，并评估未表征的细胞因子调节血管生成的能力。通过与本科实验室课程的合作，该项目将使每年60-70名学生在学习基本生物化学技术的同时参与尖端研究。优秀的学生将被邀请在学年和暑期实习期间继续他们的研究。构建人造组织或器官需要支架，理想情况下，支架既能支持细胞的三维结构，又能指导细胞的行为。这些“指令”通常是强大的蛋白质，它们与细胞相互作用，控制细胞的附着、身份、形状、运动和生长。然而，很难在不破坏这些蛋白质的情况下将它们连接到支架上。这位研究人员已经开发出一种独特的材料，可以在温和的条件下快速组装，使人们能够连接各种蛋白质而不会损害它们。这项提议将把这些具有指导性的蛋白质定位在一个三维支架上，以控制和塑造细胞的行为。由此产生的材料还将允许识别对细胞有有用作用的新蛋白质。从长远来看，这项提议中开发的方法可以适用于在同一支架上构建细胞模式(例如，在一块肝细胞中构建血管)，这是生产人造组织和器官的必要步骤。作为这项研究的一部分，研究生和本科生将接受跨学科培训。研究是STEM培训的关键组成部分，但本科生的数量超过了研究机会的数量。与休斯顿大学的一个班级合作，每年将允许60-70名本科生在学习实验室技能的同时参与这项研究。休斯顿大学拥有大量的少数民族学生。

This Career award by the Biomaterials program in the Division of Materials Research to the Texas A&M Health Science Center is to develop methods in incorporation and patterning active, structured proteins in a three-dimensional scaffold, thus greatly extending the ability to manipulate cell behavior in cell biology and tissue engineering studies. Common approaches in generating or functionalizing materials can harm sensitive molecules. Cytokines, proteins that control growth, migration, apoptosis, and differentiation, are particularly vulnerable. With this award, functionalized materials will be prepared in a single step using the Drosophila protein Ultrabithorax (Ubx). Ubx rapidly self-assembles in mild buffers, allowing cytokines that have been genetically fused to Ubx to remain active. Cytokine-Ubx fusion materials will be used to direct and pattern angiogenesis within a three-dimensional scaffold. The properties of proteins will defined that permit incorporation, benchmark the activity of cytokines embedded in materials relative to soluble monomers, and assess the ability of uncharacterized cytokines to regulate angiogenesis. By collaborating with an undergraduate laboratory course, this project will enable 60-70 students per year to participate in cutting-edge research while learning basic biochemistry techniques. Outstanding students will be invited to continue their research during the school year and in summer internships.Building artificial tissues or organs requires a scaffold, which ideally would both support cells in three dimensions and instruct cell behavior. These "instructions" are often powerful proteins which interact with the cell to control cell attachment, identity, shape, movement, and growth. However, it is difficult to attach these proteins to a scaffold without damaging them. The investigator has developed a unique material that assembles itself quickly in gentle conditions, allowing one to attach a variety of proteins without harming them. This proposal will position these instructive proteins in a three dimensional scaffold to control and pattern cell behavior. The resulting materials will also allow in identifying new proteins with useful effects on cells. In the long term, the methods developed in this proposal could be adapted to pattern cells in the same scaffold (for instance, build blood vessels in a block of liver cells), a necessary step in producing artificial tissues and organs. As part of this research, graduate and undergraduate students will receive interdisciplinary training. Research is a critical component of STEM training, but the number of undergraduates exceeds the number of research opportunities. Collaboration with a class at University of Houston, which has a large minority student population, will allow 60-70 undergraduates per year to participate in this research as they learn laboratory skills.