Biosynthesis and Reprogramming of Bacterial Organelles

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.