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From engineering to evolution of synthetic cells with RNA origami

Project description

Synthetic cells using RNA Origami

Synthetic cells, also known as artificial cells or protocells, are laboratory-created structures that mimic some of the properties and functions of natural cells. They have attracted great interest for their application in drug delivery, biotechnology and environmental sensing, as well as for advancing biomedical research. Funded by the European Research Council, the ENSYNC project aims to construct a synthetic cell by encapsulating functional biomolecules inside lipid vesicles. The goal is to achieve a self-replicating and evolving synthetic cell through programmable RNA origami structures, which direct evolution and are functionalised to perform different tasks. Apart from insights into evolutionary processes, the project will generate RNA origami-based tools for various applications.

Objective

Can we construct a cell from non-living matter? In search for answers, bottom-up synthetic biology has successfully encapsulated functional sets of biomolecules inside lipid vesicles, yet a “living” synthetic cell remains unattained. ENSYNC aims for a prototype of a synthetic cell that encompasses a fundamental characteristic of life, namely evolution. My past work shows that DNA origami can achieve custom-engineered synthetic cellular parts, but the mere encapsulation of preformed parts conflicts with the vision of a self-replicating and evolving synthetic cell. I here propose to produce and to replicate functional RNA origami structures inside of lipid vesicles (GUVs) by co-transcriptional folding from a DNA template. First, I will genetically encode an RNA nanopore and RNA origami structure which induces GUV division. The DNA template (“genotype”) will determine the GUVs’ permeability and their division rate (“phenotype”). This genotype-phenotype mapping is the basis for directed evolution of the rationally engineered RNA origami structures in the second step. In particular, I will aim for efficient GUV division in repeated cycles of genetic diversification and selection. In the third step, I will implement multiple growth and division cycles to enable continuous directed evolution. This will be achieved by system-level integration and laboratory automation of the directed evolution pipeline to iteratively reduce researcher intervention. Depending on externally applied selection pressures, continuous evolution will inevitably lead to the dominance of highly proliferating synthetic cells in mixed populations. ENSYNC provides fundamental insights into evolutionary processes as well as applicable RNA origami-based tools for nanopore sensing and as genetically encoded biophysical probes in cell biology. Overall, ENSYNC pushes the boundaries of bottom-up synthetic biology to the point where synthetic cells can be evolved towards a distinct goal in biotechnology.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2022-STG

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Host institution

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 749 624,00
Address
SEMINARSTRASSE 2
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 749 624,00

Beneficiaries (1)

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