Project description
Engineering sound-responsive cells
Gas vesicles (GVs) are tiny air-filled protein structures naturally produced by some bacteria as a means of controlling their buoyancy in water. The genes encoding GVs can be inserted into a genetic construct and transferred to target cells to produce GVs capable of reflecting sound waves during ultrasound. This makes it possible to non-invasively visualise and track the modified cells in real time. However, GV assembly in target cells is complex and has hampered their application. With the support of the Marie Skłodowska-Curie Actions programme, the ARGOS project aims to optimise GV engineering and produce more portable ARG systems. Researchers will undertake high-throughput screening and directed evolution of GV genes using synthetic biology tools to express them in yeast.
Objective
As acoustic reporter genes (ARGs), gas vesicles (GVs) have recently seen a rapid rise in biomedical interest with applications including non-invasive diagnostics and treatment. Gas filled protein nanostructures, GVs are unique, genetically encodable microbubbles that provide a stable ultrasound contrast handle. Due to their complex assembly inside of cells, the use of GVs is currently constricted to a number of wild-type, minimally engineered gene clusters and the range of cells they can be deployed to is limited. By contrast, fluorescent proteins (FPs) as optical reporter genes can readily be deployed to any biological context and decades of protein engineering have imbued them with an expansive array of colors, improved brightness, and sophisticated applications.
In this action, we aim to parallel the immense development achieved for FPs and overcome the limitations of re-engineering gas vesicles by linking their successful assembly in yeast cells to a clear optical readout, unlocking high throughput screening by FACS. Utilizing this platform, we will screen libraries of modularly assembled GV gene clusters for successful expression in S. cerevisiae. The Sc2.0 synthetic yeast genome platform will then enable the evolution of yeast genomes for superior GV assembly pathways using SCRaMbLE. Our novel GV gene clusters will be targeted for carefully guided directed (co-)evolution of one or multiple GV genes to develop synthetic GVs that provide improved contrast and phenotypes to expand their applications. To facilitate the swift engineering of ARGs for novel applications, we will obtain next-generation sequencing and single-cell RNA sequencing data of our GV genes and evolved yeast genomes to develop a deeper sequence to function understanding of GV expression in eukaryotes. This action, ARGOS, “Acoustic Reporter Gene Overhaul in Saccharomyces”, will prepare the next generation of GVs for researchers to peer beyond the limits of optical imaging.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology materials engineering colors
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences evolutionary biology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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CB2 1TN CAMBRIDGE
United Kingdom
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