INSPIRE Track 1: Protocells as a Platform for Bottom-up Synthetic Biology

小行星1344298 该INSPIRE奖部分由工程理事会CBET部门的生物技术，生物化学和生物质工程计划，生物科学理事会MCB部门的合成和系统生物学计划，数学和物理科学理事会DMR部门的生物材料计划，在这个项目中，人工细胞将被设计成具有定义的构建块，这些构建块可能小到单个基因、蛋白质和RNA。使这种方法成为可能的平台是原始细胞，这是一种通过定向自组装构建的纳米工程结构，它提供了细胞内部和表面膜的独立定义。在这种自下而上的方法中，确切地知道细胞中有什么，因此，不受控制的变量被最小化。 最初将开发概念验证，其中组装包括膜和细胞内组分的信号传导途径，随着添加更多组分而导致更大的复杂性。 最终将设计和研究具有基本功能的最小活细胞。 因此，该提案的三个主要目标是：（1）创建一个通用的合成生物学平台，以研究具有受控参数的信号转导和蛋白质合成;（2）建立控制合成细胞内信号转导和蛋白质合成的机制模型;（3）弥合体外和细胞实验之间的差距。这些目标将通过使用设计和制造的复杂程度不断增加的原始细胞的连续版本来实现。通过在系统生物学和合成生物学的背景下整合纳米科学，分子生物传感器，成像和生物化学，将建立一个高度跨学科的平台来重建和建模细胞复杂性，提供一种通用且系统的方法来理解分子网络的设计原理。细胞环境这项工作将对理解生物分子网络中的信息流和纳米级的定向自组装具有重要意义。因此，该项目的成功将对生物纳米技术和仿生设备产生变革性影响。此外，研究将与教育工作相结合，以确保本科生和高中生，特别是代表性不足的群体有机会和鼓励在尖端的跨学科研究工作。

1344298Wang This INSPIRE award is partially funded by the Biotechnology,Biochemical and Biomass Engineering Program in the CBET Division in the Directorate for Engineering, the Synthetic and Systems Biology Program in the Division of MCB in the Directorate for Biological Sciences, the Biomaterials Program in the Division of DMR in the Directorate for Mathematics and Physical Sciences, and by the Office of International and Integrative Activities.In this project artificial cells will be engineered with defined building blocks that may be as small as individual genes, proteins, and RNA. The platform that enables this approach is the protocell, a nanoengineered construct built by directed self-assembly that provides for independent definition of the cell interior and the surface membrane. In this bottom-up approach it is exactly known what is in the cell, and, therefore, uncontrolled variables are minimized. Initially a proof-of-concept will be developed in which a signaling pathway including both membrane and intracellular components is assembled, leading to greater complexity as more components are added. Ultimately a minimal living cell with basic functions will be engineered and studied. Accordingly, three major goals of the proposal are: (1) to create a general synthetic biology platform to study signal transduction and protein synthesis with controlled parameters; (2) to build mechanistic models governing the signal transduction and protein synthesis inside the synthesized cell; (3) to bridge the gap between in vitro and in cell experiments. These goals will be achieved by employing successive versions of protocells designed and fabricated with increasing levels of complexity.By integrating nanoscience, molecular biosensors, imaging, and biochemistry in the context of systems biology and synthetic biology, a highly interdisciplinary platform to reconstitute and model cellular complexity will be established providing a general and systematic approach to understand the design principles of molecular networks in a cellular environment. This work will have fundamental implications for understanding information flow in biomolecular networks and directed self-assembly at the nanoscale. As such, the success of this project will have transformative impact on bionanotechnology and biomimetic devices. In addition, the research will be integrated with educational efforts to ensure that undergraduate and high school students and particularly underrepresented groups have the opportunity and encouragement to work in cutting-edge interdisciplinary research.