Self-Assembled Protein Cage Nanoreactors

ID：MPS/dmr/bmat(7623)1104849 PI：Douglas，Trevor ORG：蒙大拿州立大学标题：自组装蛋白质笼反应器INTELCTUCTUAL优点：隔离酶反应的蛋白质壳存在于不同的生物体中，可能为功能生物材料设计提供蓝图。这项提议的目的是设计和开发一类新的生物灵感材料，利用病毒蛋白质笼组件中的酶的直接限制。这是一种将生物超分子结构与催化功能相结合的有效策略。在包封的酶保持其天然催化活性的同时，蛋白质笼可以单独优化为一个容器，可以将酶货物与其环境隔离，提高稳定性，并调节酶的活性。病毒已经成为变革性的和非常有用的材料，PI在这一领域的发展中处于领先地位。这项拟议的研究将加强病毒衣壳在生物活性材料合成应用中的使用。这种材料将极大地扩展生物技术的应用范围，使生物催化剂能够在与其进化的细胞角色截然不同的环境中使用。这项工作将进一步利用生物系统来启发、设计和合成功能材料。这项工作的具体目标是：(1)开发病毒衣壳与包括乳糖酶在内的一系列酶的程序性共组装，以扰乱细菌生物膜中的群体感应；(2)评估分子拥挤对包埋酶活性的影响；以及(3)将多个酶共同组装到病毒衣壳中，这些衣壳可以相互进行化学通信，以创建生物启发的纳米级反应器。这些酶之所以被选中，是因为它们具有极高的热稳定性，与它们作为材料构建块的用途相称。此外，这项努力将培训不同的研究生和本科生群体，使他们了解这种内在的绿色化学方法来合成纳米材料，这种方法结合了自然已经利用的非凡的材料特性。布罗德影响：这项研究有可能使生物材料、纳米技术和纳米制造等新兴领域取得重大进展。自然系统使用的生物控制机制将被用来创造新的材料和设备，以仿生的方法展示遗传程序合成来制造功能材料。这些新的病毒材料的丰富和独特的性质将使研究人员能够开发新的活性生物材料。这个项目的一个组成部分是由PI开发的一个创新的科学推广计划，该计划创造了有意义的推广经验，让本科生和研究生学习有效地交流他们的研究和他们对科学的热情。已经开发和试点的外展基础设施为教职员工和学生提供了一个模板，通过实际操作的、以探究为基础的活动，有效地分享他们对科学的兴趣。外展活动将在K-12当地公立学校以及农村和以美国原住民为主的学校举行。它们包括实地考察和举办校园活动。这一外展计划的基本目标是将积极的研究人员放在社区互动的第一线。这些活动最终导致基础科学探索，介绍当前的研究趋势和当地项目，最重要的是接触活跃的研究人员，他们成为下一代学习者的榜样和招聘者。

ID: MPS/DMR/BMAT(7623) 1104849 PI: Douglas, Trevor ORG: Montana State UniversityTitle: Self-Assembled Protein Cage ReactorsINTELLECTUAL MERIT: Protein shells that sequester enzymatic reactions are found in diverse organisms and may provide blueprints for functional biomaterials design. The aim of this proposal is to design and develop a new class of bio-inspired materials utilizing the directed confinement of enzymes within viral protein cage assemblies. This is a powerful strategy for combining biological supramolecular architectures with catalytic function. While the encapsulated enzymes retain their native catalytic activity the protein cage can be separately optimized as a container that can shield the enzymatic cargo from its environment, enhance stability, and modulate enzymatic activity. Viruses have emerged as transformational and significantly useful materials and the PI has been a leader in the development of this field. The proposed research will enhance the use of viral capsids for synthetic applications of bioactive materials. Such materials will dramatically extend biotechnology's range of applications, allowing biocatalysts to be used in contexts very different from their evolved cellular role. This work will further the use of biological systems for the inspiration, design, and synthetic implementation of functional materials. The specific aims of this work are to: (1) develop programmed co-assembly of a viral capsid with a range of enzymatic cargos including lactonases for disruption of quorum sensing in bacterial biofilms, (2) evaluate the effects of molecular crowding on the activity of the encapsulated enzymes, and (3) co-assemble multiple enzymes into the viral capsids that can chemically communicate with each other to create bio-inspired nanoscale reactors. The enzymes of interest have been selected for their extreme thermal stability commensurate with their use as materials building blocks. In addition, this effort will train a diverse group of graduate and undergraduate students in this inherently green chemistry approach to nanomaterials synthesis that incorporates the remarkable materials properties already utilized by nature.BROADER IMPACTS: This research has the potential to enable significant progress in the emerging fields of biomaterials, nanotechnology, and nano-manufacturing. Biological control mechanisms used by natural systems will be exploited to create novel materials and devices exhibiting genetically programmed synthesis in a biomimetic approach to making functional materials. The abundance and unique qualities of these new viral materials will enable researchers to develop new active bio-materials. Integral to this project is an innovative science outreach program developed by the PI that creates meaningful outreach experiences where undergraduate and graduate students learn to communicate effectively their research and their passion for science. The outreach infrastructure that has been developed and piloted provides a template for faculty and students to effectively share their interest in science through hands-on, inquiry-based events. Outreach events will take place in K-12 local public schools and with rural and predominantly Native American schools. They include site visits as well as hosting on-campus events. The fundamental goal of this outreach program is to place active researchers in the front line of community interaction. These events ultimately result in basic science exploration, introduction to current research trends and local projects, and most importantly, contact with active researchers who become role models and recruiters of the next generation of learners.