Prof. Lorenzo Di Michele
University of Cambridge, UK
Aim of this project is to design and construct synthetic cells that can conditionally produce, store and release antimicrobial RNA constructs for future applications in the targeted treatment of infections. The synthetic cells will consist of Giant Unilamellar lipid Vesicles that can enzymatically produce multivalent, branched RNA nanostructures via in-vitro transcription, as already demonstrated by the UCAM team. The DC will design new branched nanostructures comprising one or more bacteria-targeting DNA or RNA aptamers (designed in collaboration with DC11) and linking to moieties with antimicrobial properties, e.g. siRNA, antibiotics or photosensitisers. The antimicrobial moieties will either be synthesised within the synthetic cells or pre-encapsulated. For initial experiments, the synthesis and release of the antimicrobial constructs will be externally induced using light or temperature.
At later stages of the project, the DC will explore strategies to make RNA synthesis and release occur on demand, triggered by bacterial activity. Conditional RNA synthesis will be achieved either through transcription regulation by membrane-penetrating quorum sensing molecules, or exploiting nucleic acid nanotechnology solutions (e.g. pH sensitive riboswitches). Subsequent release of the accumulated antimicrobial constructs will be triggered by the delayed activation of pre-encapsulated membrane-destabilising nanostructures, already in use in the UCAM team.
In addition, the DC will explore optimised expression of the RNA constructs in bacterial hosts, providing a low-cost alternative to chemical synthesis or in vitro transcription.
Finally, the DC will study how intra-cellularly produced RNA nanostructures can alter cell behaviour and metabolism, with applications for cell and metabolic engineering.
Requirements: Degree in Physics, Chemistry, Engineering or related subject
Planned secondments: Simmel lab, Garoli lab, Micheletti group, IMEC, GattaQUANT
Salary: Payment will be as per the MSCA agreement.
The salary (36 months) is directly based on Marie Sklodowska-Curie Actions (MSCA) Doctoral Network budgeting (including a country-specific living allowance and a fixed mobility allowance for a doctoral candidate, as well as a possible family allowance).
