Self-Assembled Protein Cage Nanoreactors

ID：MPS/DMR/BMAT（7623）1104849 PI：道格拉斯，特雷弗 ORG：Montana State University蒙大拿州立大学自组装蛋白笼反应器智力优势：蛋白质外壳，螯合酶反应是在不同的生物体中发现，并可能提供蓝图的功能生物材料的设计。 该提案的目的是设计和开发一类新的生物启发材料，利用病毒蛋白笼组件内的酶的定向限制。 这是一个强大的战略结合生物超分子结构与催化功能。 虽然包封的酶保留其天然催化活性，但蛋白质笼可以单独优化为容器，其可以将酶货物与其环境屏蔽，增强稳定性并调节酶活性。 病毒已经成为转型和重要有用的材料，PI一直是这一领域发展的领导者。 拟议的研究将加强使用病毒衣壳的生物活性材料的合成应用。 这些材料将极大地扩展生物技术的应用范围，使生物催化剂能够在与其进化的细胞作用非常不同的环境中使用。 这项工作将进一步利用生物系统的灵感，设计和功能材料的合成实施。 这项工作的具体目标是：（1）开发病毒衣壳与包括内酯酶在内的一系列酶货物的程序化共组装，用于破坏细菌生物膜中的群体感应，（2）评估分子拥挤对包封酶活性的影响，以及（3）将多种酶共同组装到病毒衣壳中，所述病毒衣壳可以彼此化学通信以创建生物启发的纳米级反应器。 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，这项工作将培养一批不同的研究生和本科生在这种固有的绿色化学方法，纳米材料的合成，结合了显着的材料性质已经利用的性质。更广泛的重要性：这项研究有可能使重大进展的新兴领域的生物材料，纳米技术和纳米制造。 自然系统使用的生物控制机制将被利用来创造新的材料和设备，这些材料和设备在仿生方法中表现出遗传程序化合成，以制造功能材料。 这些新病毒材料的丰富性和独特性将使研究人员能够开发新的活性生物材料。 该项目的组成部分是由PI开发的创新科学推广计划，该计划创造了有意义的推广经验，本科生和研究生学习有效地沟通他们的研究和对科学的热情。 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，通过动手，调查为基础的活动，有效地分享他们对科学的兴趣。 外联活动将在K-12当地公立学校以及农村和主要是美洲原住民学校举行。 他们包括现场访问以及举办校园活动。 这个外展计划的基本目标是把积极的研究人员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，与活跃的研究人员接触，他们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.