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)
The project will start in October 2018. It is a 4-year funding for UK/EU nationals who meet RCUK residency requirements, covering stipend at RCUK rate (£14,553 per annum for 2017-2018), tuition fees, research and training costs
Highly-motivated applicants with experience in biochemistry, biophysics, nanotechnology or relevant areas should apply. Experience in electron and atomic force microscopy is an advantage. Review will begin on 05/02/2018 and continue until a suitable candidate is identified. Application with CV and a cover letter showing motivation, skills and qualifications for the project and two referees’ contacts should be sent to Dr Luning Liu ([Email Address Removed]).
1. Direct characterization of the native structure and mechanics of cyanobacterial carboxysomes. Faulkner M, Rodriguez-Ramos J, Dykes GF, Owen SV, Casella S., Simpson DM, Beynon RJ, Liu LN. Nanoscale, 2017, 9(30): 10662-10673.
2. Assembly principles and structure of a 6.5-MDa bacterial microcompartment shell. Sutter M, Greber B, Aussignargues C, Kerfeld CA. Science. 2017 Jun 23;356(6344):1293-1297.
3. Visualization of bacterial microcompartment facet assembly using high-speed atomic force microscopy. Sutter M, Faulkner M, Aussignargues C, Paasch BC, Barrett S, Kerfeld CA, Liu LN. Nano Letters, 2016, 16(3): 1590-1595.