Programmable 2- and 3-Dimensional Protein Assemblies

可编程 2 维和 3 维蛋白质组装体

• 批准号: 1602537
• 负责人: Faik Tezcan
• 金额: $ 42万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1602537&HistoricalAwards=false
• 关键词: Programmable; Dimensional; Protein; Assemblies

Nontechnical: Under this award from the Biomaterials Program in the Division of Materials Research to University of California-San Diego, the researcher will develop new chemical approaches for the design and engineering of novel protein assemblies. This award is co-funded by the following programs: 1) BioMaPS program in the Division of Materials Research; and 2) Biotechnology and Biochemical Engineering program in the Division of Chemical and Bioengineering, Environmental, and Transport Systems (ENG). Proteins are nature's premier building blocks in constructing complex biological systems such as the photosynthetic machinery or for building sophisticated materials with advanced physical and chemical properties such as the human skin and bone. However, proteins are remarkably complex molecules with non-uniform surfaces and structures, and the ability to control the self-assembly of proteins or to use them as synthetic building blocks has been limited. In this project, the assembly of supramolecular protein architectures will be studied by using new approaches of chemical bonding and self-assembly strategies that are expected to give rise to new classes of synthetic protein assemblies. Such an ability to construct complex biological structures in a bottom-up fashion from multiple components will not only provide fundamental insights into biological self-assembly processes, but will also lend access to novel protein-based functionalities and materials with potential applications in bio/nanotechnology and biomedical applications such as drug/gene transport and tissue regeneration. As part of the teaching and training, this project will provide training for postdoctoral, graduate, undergraduate, and high school researchers in supramolecular chemistry, molecular biology, protein biochemistry, crystallography, biophysical techniques, and computational protein design. The PI's outreach efforts will be expanded on several different fronts, including active recruitment of members of underrepresented minority groups for research. High school students will be recruited through various self-initiated and campus-supported programs, and with involvement in science fairs at local elementary schools.Technical: This multidisciplinary project is based on the application of supramolecular chemistry principles, protein engineering and molecular biology to the study and control of protein self-assembly. Protein building blocks with appropriately chosen structures/symmetries will be designed to assemble into prescribed supramolecular assemblies through disulfide bonding, electrostatic and designed surface interactions. The main goal of this project is to expand the capability to construct supramolecular protein architectures by utilizing non-inorganic modalities of chemical bonding and self-assembly strategies that circumvent the need for designing extensive interfaces. This goal will be accomplished through three objectives: 1) in developing molecular design strategies for the disulfide-directed assembly of homomeric, 2 and 3-D protein arrays and architectures; 2) in implementing auxiliary interactions and surface-templating strategies for improved control of disulfide-directed protein assembly; and 3) in constructing DNA-directed 2- and 3-D crystalline protein arrays. Physical, biochemical and structural properties of these assemblies will be characterized by a large suite of techniques including electron microscopy and diffraction, atomic force microscopy, protein crystallography, and solution biophysical methods. The resulting protein architectures and hybrid materials could be utilized for materials applications such as templating of inorganic nanoparticles and encapsulation of various types of molecular cargos. The proposed activities would expand the current understanding for designing highly ordered 2 and 3D protein nanostructures from the bottom up, and would likely aid a broad range of researchers in building protein-based nanomaterial structures. The researcher has an impressive track record in recruiting and mentoring underrepresented minority students in research activities, and plans are provided to expand these activities.

非技术性：根据加州大学圣地亚哥分校材料研究部生物材料项目的这一奖项，研究人员将开发新的化学方法来设计和工程化新型蛋白质组装体。该奖项由以下项目共同资助：1）材料研究部的BioMaPS项目; 2）化学和生物工程，环境和运输系统（ENG）部的生物技术和生物化学工程项目。蛋白质是构建复杂生物系统（如光合作用机制）或构建具有先进物理和化学特性的复杂材料（如人类皮肤和骨骼）的主要组成部分。然而，蛋白质是非常复杂的分子，具有不均匀的表面和结构，并且控制蛋白质的自组装或将其用作合成构件的能力受到限制。在这个项目中，超分子蛋白质结构的组装将通过使用化学键合和自组装策略的新方法进行研究，这些方法有望产生新的合成蛋白质组装。这种从多个组件以自下而上的方式构建复杂生物结构的能力不仅将提供对生物自组装过程的基本见解，而且还将提供对具有生物/纳米技术和生物医学应用（例如药物/基因运输和组织再生）中的潜在应用的新型基于蛋白质的功能和材料的访问。作为教学和培训的一部分，该项目将为博士后，研究生，本科生和高中研究人员提供超分子化学，分子生物学，蛋白质生物化学，晶体学，生物物理技术和计算蛋白质设计的培训。PI的外展工作将在几个不同的方面扩大，包括积极招募代表性不足的少数群体成员进行研究。高中生将通过各种自发和校园支持的项目招募，并参与当地小学的科学展览会。技术：这个多学科项目是基于超分子化学原理，蛋白质工程和分子生物学的应用，以研究和控制蛋白质自组装。具有适当选择的结构/对称性的蛋白质结构单元将被设计为通过二硫键、静电和设计的表面相互作用组装成规定的超分子组装体。该项目的主要目标是扩大能力，通过利用非无机形式的化学键合和自组装策略，规避设计广泛的接口的需要，构建超分子蛋白质架构。这一目标将通过三个目标来实现：1）开发用于同源、2-D和3-D蛋白质阵列和架构的二硫键定向组装的分子设计策略; 2）实施辅助相互作用和表面模板策略以改进二硫键定向蛋白质组装的控制;以及3）构建DNA定向的2-D和3-D晶体蛋白质阵列。这些组件的物理，生物化学和结构特性将通过一系列技术来表征，包括电子显微镜和衍射，原子力显微镜，蛋白质晶体学和溶液生物物理方法。所得的蛋白质结构和杂化材料可用于材料应用，如无机纳米颗粒的模板化和各种类型的分子货物的封装。拟议的活动将扩大目前对自下而上设计高度有序的2D和3D蛋白质纳米结构的理解，并可能有助于广泛的研究人员构建基于蛋白质的纳米材料结构。研究人员在招募和指导研究活动中代表性不足的少数民族学生方面有着令人印象深刻的记录，并计划扩大这些活动。