Modularity and Synthetic Engineering of carbon-fixing organelles

Compartmentalisation represents an effective strategy designed by cells to enhance their activities. By creating subcellular organelles, cells sequester key metabolic pathways from the cellular milieu to allow controls of metabolic flux and toxic diffusion. Recently, compartmentalisation has been increasingly seen in a range of prokaryotic lineages that are relevant to human health and the environment, giving rise to several types of nanoscale bacterial organelles. An intriguing example is the carboxysome, which outstandingly enhances photosynthetic carbon fixation in cyanobacteria. Carboxysomes are composed of hundreds of proteins that self-assemble, in a precise and regulatory manner, to form a highly-organised and functional architecture. Such organelles offer excellent opportunities for bioengineering of metabolic modules.

This project will use multidisciplinary approaches, including molecular genetics, biochemistry, microscopy and synthetic biology, to study how carboxysomes are constructed in nature and how to engineer carboxysomes with new functions. This work represents a model for studying the biogenesis of complex biological machines within cells. It will teach us about how thousands of proteins can assemble together by themselves to form a functional entity within cells, and what regulatory strategies are developed by the cells to lead the development and function of these machines. In translational terms, this work will provide an instructive example for the design and engineering of novel biological “factories”, for specific metabolic activities and the development of new therapeutic strategies. It has the potential to revolutionise crop engineering, bioenergy production and therapeutic development.

The multidisciplinary nature of this project provides the student with a great opportunity for academic training in molecular biology, biochemistry, biophysics and synthetic biology. The laboratory of Dr. Liu (http://www.luningliu.org) has experience in protein self-assembly using biochemical and biophysical techniques (Plant Physiol 2016; Nano Letters 2016; PNAS 2012; PNAS 2011). The multidisciplinary skills and expertise of the Liu group and the collaborating network crossing UK and the world will guarantee the success of this project. The Institute of Integrative Biology will provide essential facilities for this project, including a Centre for Cell Imaging centre for cell and molecular imaging, core genomic sequencing and proteomic platforms, centres for NMR, X-ray and SAXS, Computational Modelling as well as new synthetic biology foundry – Liverpool GeneMill. Training in all aspects of the project will be provided with access to state-of-the-art infrastructure in the Institute and with collaborators in UK, Europe, Australia, US and China, which means that there will be great opportunities for career development.