CAREER: The Molecular Structure of Type II Collagen by Fiber Crystallography

职业：通过纤维晶体学研究 II 型胶原蛋白的分子结构

• 批准号: 0644015
• 负责人: Joseph Orgel
• 金额: $ 87.96万
• 依托单位: Illinois Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0644015&HistoricalAwards=false
• 关键词: CAREER; Molecular; Structure; Type; II

Summary: The collagens are important structural proteins. They form the infrastructure of all mammalian organs as well as blood vessels, skin, bones and cartilage. Understanding how these proteins interact and are affected by normal growth, developmental and repair processes in mammals, and therefore humans, requires knowledge of how collagen is organized in its natural state. Some connective tissues, such as those formed chiefly by type II and type I collagen are naturally crystalline, a fact that can be usefully exploited by using certain X-ray diffraction techniques to image the molecular structure of collagen whilst keeping the sample tissue intact. This project will build on a number of developments in the Orgel lab that were previously used to determine the natural, intact, structure of Type I collagen. The first goal of this project is to apply these innovations in diffraction imaging to determining the natural, intact, structure of type II collagen. It is expected that so doing will have significant impact, due to type II collagens key role in growth and development and the shared roles and interactions between collagen types II and I. The second goal of the project is to advance the developing field of "Fiber Crystallography" by: development of X-ray diffraction techniques adapted from "macromolecular crystallography", optimizing cryogenic-preservation strategies for samples, development of micrometer scale diffraction methods, engaging in dissemination activities, training of students and educational outreach to the local community. This focused effort should result, not only in a greatly improved understanding of the molecular architecture of fibrous connective tissue but also in substantial advances for the emerging field of fiber crystallography, which includes the training of personnel and future scientists who will one day become the practitioners of this and other biophysical disciplines.Broader impact and Outreach: The impact of this project is enhanced by leadership roles undertaken by the Principal Investigator. The PI is the chair-elect of the American Crystallographic Associations Fiber Diffraction Special Interest Group (Fiber SIG) and a core member of the NSF supported Fiber diffraction Research Collaborative Network (RCN). These roles support and enhance his ability to conduct outreach and dissemination of the activities conducted during this project. As Associate Director for Fiber Crystallography at the Biophysics Collaborative Access Team facility (BioCAT), Advanced Photon Source (APS), Argonne, IL, the PI is responsible for technical developments for fiber crystallography WAXS and micro-diffraction instruments and the development of the scientific community in these areas. This mandate, to develop highly optimized facilities for the scientific community, will also greatly enhance the probability of success of this project whilst providing a position of scientific leadership from which he can disseminate his findings, and facilitate the training and mentoring of young scientists in the biophysical disciplines (including fiber- and macromolecular crystallography). These activities are exceptionally synergistic with this project, representing a substantial leveraging of NSF resources. The educational value of this project partly rests with the way in which the research phases are organized in discrete modules, in order to allow undergraduate and high-school students to make tangible contributions to the research project alongside graduate, post-graduate and faculty team members in a vertically integrated research team. Student personnel are recruited from the institution and surrounding area (which is predominantly low-income African-American and Latino) through a variety of institution based programs or as part-time research assistants. The latter approach helps develop a sense of 'real-world' professionalism and dedication.

胶原蛋白是重要的结构蛋白。它们构成所有哺乳动物器官以及血管、皮肤、骨骼和软骨的基础结构。了解这些蛋白质如何相互作用，并受到哺乳动物和人类正常生长，发育和修复过程的影响，需要了解胶原蛋白在其自然状态下是如何组织的。一些结缔组织，如主要由II型和I型胶原形成的结缔组织是天然结晶的，这一事实可以通过使用某些X射线衍射技术来有效地利用，以成像胶原的分子结构，同时保持样品组织完整。该项目将建立在Orgel实验室的一些发展基础上，这些发展以前用于确定I型胶原蛋白的天然，完整的结构。该项目的第一个目标是将这些创新应用于衍射成像，以确定II型胶原蛋白的天然，完整的结构。由于II型胶原在生长和发育中的关键作用以及II型和I型胶原之间的共同作用和相互作用，预计这样做将产生重大影响。该项目的第二个目标是推动“纤维晶体学”这一正在发展中的领域，具体做法是：发展根据“大分子晶体学”改编的X射线衍射技术，优化样品的低温保存策略，发展微米级衍射方法，开展传播活动，培训学生和向当地社区开展教育宣传。这种集中的努力不仅会大大提高对纤维结缔组织分子结构的理解，而且会在纤维晶体学的新兴领域取得实质性进展，其中包括培训人员和未来的科学家，他们有朝一日将成为该学科和其他生物物理学科的从业者。该项目的影响因主要研究员发挥的领导作用而得到加强。PI是美国晶体学协会纤维衍射特别兴趣小组（Fiber SIG）的当选主席，也是NSF支持的纤维衍射研究合作网络（RCN）的核心成员。这些作用支持并加强了他对本项目期间开展的活动进行外联和传播的能力。作为生物物理协作访问团队设施（BioCAT），高级光子源（APS）（阿贡，IL）的纤维晶体学副主任，PI负责纤维晶体学WAXS和微衍射仪器的技术开发以及这些领域科学界的发展。这一任务是为科学界开发高度优化的设施，这也将大大提高该项目成功的可能性，同时提供一个科学领导地位，他可以传播他的发现，并促进生物物理学科（包括纤维和大分子晶体学）的年轻科学家的培训和指导。这些活动与本项目具有特别的协同作用，代表了对NSF资源的大量利用。该项目的教育价值部分在于研究阶段以离散模块组织的方式，以便让本科生和高中生与研究生，研究生和教师团队成员一起在垂直整合的研究团队中为研究项目做出切实贡献。学生人员从机构和周边地区（主要是低收入的非洲裔美国人和拉丁美洲人）通过各种基于机构的计划或兼职研究助理招募。后一种方法有助于培养“现实世界”的专业精神和奉献精神。