Designed Collagen Heterotrimeric Helices and Nanofibrous Hydrogels

ID: MPS/DMR/BMAT(7623) 1206899 PI: Hartgerink， Jeffrey ORG: Rice university标题：设计的胶原异三聚体螺旋和纳米纤维水凝胶知识分子优点：胶原蛋白是人体中最丰富的蛋白质，可以说是自然界中最重要的蛋白质之一，在几乎所有组织中起着关键作用，尤其是骨骼，皮肤和肌腱。此外，胶原蛋白在许多疾病中起着重要作用，如癌症的转化和各种脆性骨疾病。尽管胶原蛋白至关重要，但人们对其结构和最终形成纤维状的组装过程知之甚少。在该基金资助的工作中，莱斯大学的Hartgerink实验室将通过合成、分析和计算建模的迭代过程，专注于理解这种关键分子。将制备与胶原蛋白结构相似的分子，并通过核磁共振波谱、x射线晶体学和透射电子显微镜等多种分析方法确定其结构。基于这些发现，将准备一个模型来预测新的和更复杂的胶原结构。这个过程将允许创建一个蓝图，定义天然胶原蛋白如何组装，以及如何化学合成和自组装结构复杂的胶原蛋白模拟物。更广泛的影响：预计该蓝图将增强对这一重要生物分子的认识，并为生物材料研究人员创造一个有用的工具。本拨款提案中描述的研究也将作为本科和研究生教育项目的基础，有效地将化学设计和合成与传统结构生物学结合起来，成为一个令人兴奋的多学科研究。此外，通过中学教育推广计划，高中科学教师将有机会在暑假期间参加研究实验室，根据当前的研究开发创新的课程模块，这些模块可以直接应用于高中化学和生物课程。

ID: MPS/DMR/BMAT(7623) 1206899 PI: Hartgerink, Jeffrey ORG: Rice UniversityTitle: Designed Collagen Heterotrimeric Helices and Nanofibrous HydrogelsINTELLECTUAL 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.