CAREER: Molecular Level Investigation of Peptide Recognition on Hydroxyapatite

该职业奖由加州大学伯克利分校材料研究部生物材料项目颁发，旨在全面了解明确定义的羟基磷灰石（HAP）晶体与其识别肽之间的相互作用，以及这种矿化是如何调节的。在分子水平上了解蛋白质如何调节生物矿化过程对于理解骨化、骨质疏松症和许多其他骨和牙齿相关疾病至关重要。在本项目中，研究者将合成（100）和（001）HAP表面，并研究HAP晶体的表面结构。下一步将是鉴定特异性结合明确定义的（100）和（001）表面的肽，并在生物学相关条件下表征其结合特异性。利用各种显微镜和定量分析技术，研究者将表征识别肽与HAP晶体表面之间的纳米级相互作用，并验证HAP结合肽的作用。这项研究的成功完成将为明确定义的（100）和（001）HAP表面提供特定的识别肽基序。由此产生的HAP识别肽可用于设计硬组织再生材料和/或开发新型小分子药物来抑制不希望的矿化过程。此外，所提出的研究可能有助于开发基于蛋白质的骨假体再生材料和骨相关疾病的新疗法，如骨质疏松症和成骨不全症。该项目的教育目标将为当前和未来的生物科学和生物工程研究人员提供学习机会。该项目将为生物工程系的本科生和研究生开设新课程，在加州大学伯克利分校创建一个新的“生物生物学”系列研讨会，并在当地社区组织会议。将创建一个基于网络的数据库，展示从噬菌体展示中鉴定的HAP结合肽序列，并对肽与HAP的相互作用进行原位AFM分析。它还将为研究人员提供其他骨骼和牙齿相关蛋白质的有组织的总结。为了鼓励后代从事科学和工程，PI将与本科生和研究生合作，开发一个动手展览和实验，以加深对蛋白质在使用贝壳和骨骼的生物科学中的作用的理解。这个名为“寻找纳米”的展览将在科学博物馆的劳伦斯大厅（伯克利，加州）以及当地低收入的小学展出。

This Career award by the Biomaterials program in the Division of Materials Research to University of California Berkeley is to develop a comprehensive understanding of the interactions between well-defined hydroxyapatite (HAP) crystals and their recognition peptides and how this mineralization is regulated. A molecular level understanding of how proteins regulate the biomineralization process is critical for understanding ossification, osteoporosis, and many other bone- and tooth-related diseases. With this project, the investigators will synthesize (100) and (001) HAP surfaces and study the surface structures of HAP crystals. The next step will be identification of peptides that specifically bind to the well-defined (100) and (001) surfaces and characterize their binding specificity under biologically relevant conditions. Using various microscopy and quantitative analysis techniques, the investigator will characterize the nanoscopic interactions between the recognition peptides and HAP crystal surfaces and verify the roles of the HAP-binding peptides. The successful completion of this research will provide specific recognition peptide motifs for well defined (100) and (001) HAP surfaces. The resulting HAP recognition peptides may be useful for designing hard tissue regenerating materials and/or for developing novel small molecule-based drugs to inhibit undesired mineralization processes. In addition, the proposed studies may be useful for developing protein-based bone prosthetic regeneration materials and novel therapeutics for bone related diseases such as osteoporosis and osteogenesis imperfecta.The educational aims of the project will provide learning opportunities for current and future researchers in bionanoscience and bioengineering. The PI will develop new courses at the undergraduate/graduate levels in the Department of Bioengineering, create a new seminar series on "Bionanoscience" at UC Berkeley, and organize conferences in local communities. A web-based database presenting the HAP-binding peptide sequences identified from phage display and in situ AFM analysis of the peptide interactions with HAP will be created. It will also provide researchers with an organized summary of other bone- and tooth- associated proteins. To encourage future generations to be engaged in science and engineering, the PI will work with undergraduate and graduate students to develop a hands-on exhibit and experiments to enhance the understanding of the role of proteins in bionanoscience using seashells and bones. This exhibit, entitled "Finding Nano", will be presented at the Lawrence Hall of Science Museum (Berkeley, CA), as well as to local low-income elementary schools.