CAREER: Molecular Level Investigation of Peptide Recognition on Hydroxyapatite

这一职业奖项由加州大学伯克利分校材料研究部的生物材料项目颁发，旨在全面了解定义明确的羟基磷灰石(HAP)晶体及其识别肽之间的相互作用，以及这种矿化是如何受到调控的。在分子水平上了解蛋白质如何调节生物矿化过程，对于了解骨化、骨质疏松症和许多其他与骨骼和牙齿相关的疾病至关重要。在这个项目中，研究人员将合成(100)和(001)HAP表面，并研究HAP晶体的表面结构。下一步将是鉴定与明确定义的(100)和(001)表面特异结合的多肽，并在生物相关的条件下表征它们的结合特异性。利用各种显微镜和定量分析技术，研究人员将表征识别肽与HAP晶体表面之间的纳米相互作用，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多肽基序。由此得到的HAP识别多肽可能有助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看到的矿化过程。此外，建议的研究可能有助于开发基于蛋白质的骨假体再生材料，以及治疗骨质疏松和成骨不全等骨相关疾病的新疗法。该项目的教育目标将为现有和未来的生物无机学和生物工程研究人员提供学习机会。国际生物工程学会将在生物工程系开发新的本科生/研究生课程，在加州大学伯克利分校开设新的“生物科学”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，展示通过噬菌体展示和原位AFM分析与HAP相互作用的肽的HAP结合肽序列。它还将为研究人员提供其他与骨骼和牙齿相关的蛋白质的有组织的摘要。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，以加强对蛋白质在使用贝壳和骨骼的生物嗅觉科学中作用的理解。这场名为《发现纳米》的展览将在加州伯克利的劳伦斯科学博物馆以及当地的低收入小学展出。

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.