INTELLECTUAL MERIT: Collagen is the most abundant protein in the human body and arguably one of the most important proteins in nature, playing a critical role in nearly every tissue especially bone, skin, and tendons. Furthermore, collagen plays a major role in many diseases such as metathesis in cancer and a variety of brittle bone diseases. Despite collagen's critical importance, its structure and the assembly process that leads to its final fibrous form is poorly understood. In the work funded through this grant, the Hartgerink lab at Rice University will focus on understanding this critical molecule through an iterative process of synthesis, analysis, and computational modeling. Molecules, which closely mimic collagen's structure, will be prepared and their structure determined through a variety of analytical methods including nuclear magnetic resonance spectroscopy, X-ray crystallography, and transmission electron microscopy. Based on these findings, a model will be prepared to predict new and more complicated collagen structures. This process will allow a blueprint to be created that will define how natural collagen assembles as well as how one can chemically synthesize and self-assemble structurally sophisticated mimics of collagen.
BROADER IMPACTS: It is expected that this blueprint will enhance the knowledge of this centrally important biological molecule as well as create a useful tool for biomaterials researchers. The research described in this grant proposal will also be used as the basis for undergraduate and graduate educational programs that effectively combine chemical design and synthesis with traditional structural biology into an exciting multidisciplinary study. Furthermore, through a secondary education outreach program, high school science teachers will have an opportunity to participate in a research lab over summers to develop innovative curriculum modules based on current research that can be directly implemented in high school level chemistry and biology courses.
