Self-Assembled Protein Cage Nanoreactors

ID: MPS/DMR/BMAT(7623) 1104849 PI：道格拉斯，特雷弗ORG：蒙大拿州立大学标题：自组装蛋白质笼反应器智力优点：蛋白质壳，隔离酶反应被发现在不同的生物体，并可能提供蓝图的功能生物材料设计。本提案的目的是设计和开发一种新型的生物启发材料，利用病毒蛋白笼组件中的酶的定向限制。这是一种将生物超分子结构与催化功能相结合的有力策略。当被封装的酶保持其天然的催化活性时，蛋白质笼可以单独优化为一个容器，可以保护酶货物免受其环境的影响，增强稳定性，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一直是这一领域发展的领导者。提出的研究将加强利用病毒衣壳合成生物活性材料的应用。这些材料将极大地扩展生物技术的应用范围，使生物催化剂能够用于与它们进化的细胞作用截然不同的环境中。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)开发病毒衣壳与一系列酶货物的程序化共组装，包括用于破坏细菌生物膜中群体感应的内酯酶；(2)评估分子拥挤对被封装酶活性的影响；(3)将多种酶共组装到病毒衣壳中，这些酶可以相互化学沟通，以创建生物启发的纳米反应器。选择感兴趣的酶是因为它们的极端热稳定性与它们作为材料构建块的用途相称。此外，这项工作将培养多样化的研究生和本科生群体，在这种固有的绿色化学方法中合成纳米材料，结合自然界已经利用的卓越材料特性。更广泛的影响：这项研究有可能在生物材料、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利用来创造新型材料和设备，这些材料和设备展示了以仿生方法制造功能材料的遗传程序合成。这些新的病毒材料的丰富和独特的品质将使研究人员能够开发新的活性生物材料。这个项目的组成部分是由PI开发的一个创新的科学推广项目，它创造了有意义的推广体验，让本科生和研究生学会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师和学生提供了一个模板，通过实践和基于探究的活动有效地分享他们对科学的兴趣。推广活动将在当地的K-12公立学校以及农村和主要是印第安人学校举行。它们包括实地考察以及举办校园活动。这项外展计划的基本目标是将活跃的研究人员置于社区互动的前线。这些活动的最终结果是基础科学探索，介绍当前的研究趋势和当地项目，最重要的是，与活跃的研究人员接触，这些研究人员成为下一代学习者的榜样和招聘人员。

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.