PROTOBAC · Engineering of complex protocells by micro-compartmentalization of living bacteria

The engineering of artificial cellular systems (i.e. protocells) exhibiting rudimentary life-like properties, such as minimal metabolism, sensing or replication, gene expression and compartmentalization, represents the most suitable path to undertake to answer the important question on how inanimate systems can transition into proto-living manifestations of physical matter. However, most of the current protocell designs still lack the structural and organisational complexity required for them to perform advanced functions and behaviours. Instead of starting from non-living materials, the aim of this proposal is precisely to design and construction of complex multi-component protocells based on the controlled sequestration and disruption of compartmentalized living bacterial colonies. The result protocells will bound by an assemblage of bacterial membrane lipids and internally loaded with a large number of functionally active metabolic and genetic components. Furthermore, the structural and functional complexity of the bacteria-derived protocells will be increased by introducing several important biological organelles such as proto-nuclear, proto-mitochondria components and endomembrane system, which is expected to produce the first example of protoeukaryote. The previous expertise of the applicant in the field of biotechnology, synthetic biology and microbiology will be applied to the multidisciplinary and emerging field of protocells in which the hosting group of Professor Stephen Mann FRS at the University of Bristol has been pioneering over the last few years. The key outcome of the combined research efforts of the applicant and the Mann group will lead to the synthesis of bacteria derived protocells and develop their advanced forms capable of increased energy (metabolic) capacity and transduction, spatial segregation of genetic material (plasmids etc), and higher-order organization and processing.