Programmable 2- and 3-Dimensional Protein Assemblies

非技术性：根据材料研究部生物材料计划授予加州大学圣地亚哥分校的这一奖项，研究人员将为新型蛋白质组件的设计和工程开发新的化学方法。该奖项由以下项目共同资助：1)材料研究部的BioMaPS项目；以及2)化学和生物工程、环境和运输系统(ENG)部门的生物技术和生化工程项目。蛋白质是构建复杂生物系统(如光合作用机械)或构建具有高级物理和化学特性的复杂材料(如人类皮肤和骨骼)的主要自然构件。然而，蛋白质是非常复杂的分子，具有不均匀的表面和结构，控制蛋白质自组装或将其用作合成构件的能力一直受到限制。在这个项目中，将使用新的化学键和自组装策略来研究超分子蛋白质结构的组装，这有望产生新的合成蛋白质组装类别。这种从多个组分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，而且还将使人们能够获得基于蛋白质的新功能和材料，这些功能和材料在生物/纳米技术以及药物/基因运输和组织再生等生物医学应用中具有潜在的应用。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、结晶学、生物物理技术和计算蛋白质设计方面的培训。国际和平协会的外联工作将在几个不同的战线上扩大，包括积极招募代表人数不足的少数群体成员进行研究。高中生将通过各种自行发起和校园支持的项目招募，并参与当地小学的科学博览会。技术：这个多学科项目基于超分子化学原理、蛋白质工程和分子生物学在蛋白质自组装研究和控制中的应用。具有适当选择的结构/对称性的蛋白质构建块将被设计成通过二硫键、静电和设计的表面相互作用组装成指定的超分子组件。该项目的主要目标是通过利用非无机形式的化学键和自组装策略来扩大构建超分子蛋白质结构的能力，从而避免设计广泛的接口。这一目标将通过三个目标来实现：1)开发用于同质、2和3-D蛋白质阵列和结构的二硫键导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，以改进对二硫键导向蛋白质组装的控制；以及3)构建DNA导向的2-D和3-D结晶蛋白质阵列。这些组装体的物理、生化和结构特性将通过一大套技术来表征，包括电子显微镜和衍射、原子力显微镜、蛋白质结晶学和溶液生物物理方法。由此得到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2和3D蛋白质纳米结构的理解，并可能帮助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族裔学生方面有着令人印象深刻的记录，并提供了扩大这些活动的计划。

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.