Nanomechanics of bacterial carbon-fixation organelles

Bacterial microcompartments are nano-scale organelles found in many bacteria, which are formed by the self-assembly of hundreds of proteins and molecules into one well-defined structure. They are of great importance in enhancing specific metabolic reactions. Understanding how these organelles are formed and maintained in the cell is vital for the engineering of functional organelles. How do cells manage to assemble many hundreds of proteins into one complex structure with efficient metabolic functions? How do different building blocks contribute to the self-assembly and whole-organelle functionality? What are the intrinsic mechanical properties of these 3D structures? This PhD project will explore the basic physical principles of bacterial microcompartments, termed carboxysomes, which are essential for carbon fixation. We will use state-of-the-art microscopy technique named atomic force microscopy, combined with molecular genetics, biochemistry and synthetic biology, to determine the mechanical forces during the structural deformation of the organelles and the self-assembly process of individual proteins at the molecular resolution. By doing so, we will achieve the mechanical “fingerprints” of natural and designed organelles, and understand how these structural building blocks assemble in a controllable manner to form and stabilise the entire organelles. Our goal is to provide essential information to guide the design, engineering and the ultimate manipulation of metabolic factories in a predictive context. The research outputs will have broader applications in the field of self-assembling organelles and protein engineering to generate new nanoreactors and scaffolding biomaterials. Lessons learned from this biological system are also instrumental to studies in physics, chemistry, nanotechnology and bioengineering. Training in all aspects of the project will be provided with access to state-of-the-art infrastructure in the University and with collaborators in the UK, Europe, US, Australia and China, which means that there will be good opportunity for career development.

(For more details about the project, please see www.luningliu.org)