Biosynthesis and Reprogramming of Bacterial Organelles

自组装是自然界中从分子、蛋白质、细胞器到整个细胞等不同尺度的生物系统的基本构建过程。碳酶体是蓝藻中特有的蛋白质细胞器，它具有固定CO2的功能，对全球CO2固定有重要贡献。CO2固定酶Rubisco和碳酸酐酶通过多个蛋白质组分平铺的多面体蛋白质壳隔离在羧基体内，该多面体蛋白质壳作为特定分子通过的选择性渗透屏障。自组装，模块化和壳渗透性使羧基体成为工程催化工厂和开发新的纳米材料和分子支架的特殊系统，目的是增强细胞代谢，提高作物CO2同化和生产力，了解自然发生的生物机器是如何合成的，对于功能生物系统的设计和合成工程至关重要，生物技术应用。最近，我们已经合成了一个羧基壳，具有类似的性质作为本地的。该系统是理想的基本理解的羧基体形成和合成工程的羧基体为基础的结构。本博士项目将利用微生物学、生物化学、生物物理学和合成生物学等跨学科方法，探索羧基体壳组装和形成的分子基础，并开发体内和体外平台，将羧基体壳工程化为新的纳米生物反应器。本项目建立在刘教授在羧基体生物化学和工程、光合作用、碳同化、显微镜、合成生物学、生物化学、以及霍华德博士在生物技术、生物工程和无细胞重组方面的专业知识，以及马尔斯-赖特博士在结构生物学和冷冻电子显微镜方面的专业知识。研究结果将提供策略，用于调节基于羧基体的纳米结构的生物合成，以增强代谢和生物催化剂的新功能。

Self-assembly is a fundamental construction process of natural biological systems at different scales, ranging from molecules, proteins, organelles to the whole cell. Carboxysomes are the special protein organelles found in all cyanobacteria, which fix CO2 and contribute significantly to global CO2 fixation. The CO2-fixing enzymes Rubisco and carbonic anhydrase are sequestered within the carboxysome by a polyhedral protein shell tiled with multiple protein components, which serves as a selectively permeable barrier to the passage of specific molecules. The self-assembly, modularity, and shell permeability make carboxysomes an exceptional system for engineering catalytic factories and developing new nanomaterials and molecular scaffolds, with the aims of enhancing cellular metabolism, improving crop CO2 assimilation and productivity, and underpinning molecule delivery.Understanding how naturally occurring biological machines are synthesised is vital for the design and synthetic engineering of functional biosystems in biotechnological applications. Recently, we have generated synthetically a carboxysome shell that possesses similar properties as the native one. This system is ideal for fundamental understanding of carboxysome formation and synthetic engineering of carboxysome-based structures. Using interdisciplinary approaches including microbiology, biochemistry, biophysics, and synthetic biology, this PhD project will explore the molecular basis of the assembly and formation of carboxysome shells, and develop in vivo and in vitro platforms to engineer carboxysome shells as new nanobioreactors.This project builds on the expertise of Prof Liu in carboxysome biochemistry and engineering, photosynthesis, carbon assimilation, microscopy, synthetic biology, as well as the expertise of Dr Howard in biotechnology, bioengineering and cell-free reconstitution and Dr Marles-Wright in structural biology and cryo-electron microscopy. The research outcome will provide strategies for modulating the biosynthesis of carboxysome-based nanostructures for enhanced metabolism and biocatalysts for new functions.