Career: Using Functionalized Protein-Based Materials To Control and Pattern Cell Behavior
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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.