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Design of Nucleic Acid-Templated Ordered Protein Assemblies

Project description

Nucleic acid templates: flexible use in the design of novel protein assemblies

Proteins are the workhorses of cells, enabling most cellular functions including signalling, recognition and immunity by acting as catalysts, signal receptors, switches, motors and tiny pumps. Mimicking these roles with engineered protein assemblies can support applications in areas from biomedicine to energy and the environment. The European Research Council-funded DNA-TO Pass project will combine two cutting-edge areas of science, DNA nanotechnology and protein design, to create a new class of engineered nanomaterials. Using nucleic acid templates in three different approaches, they will control the assembly and final characteristics of protein assemblies. The synergy between DNA nanotechnology and protein design will unlock properties previously inaccessible.

Objective

Here I propose to create a new class of designed nanomaterials that will combine the advantageous features of protein design and DNA nanotechnology: nucleic acid-templated protein assemblies. I propose three different approaches that all utilize the addressability of nucleic acids on the nanometer to micrometer length scale to control size, shape, and composition of designed protein assemblies.
In the first approach, the structural and mechanical properties of the assembly will be defined by the protein components, while the nucleic acid component serves merely to define the dimensions of the assembly and to introduce addressability to an otherwise symmetric, repetitive assembly. All components, including the nucleic acid template, can be genetically encoded, potentially enabling assembly of entire nanoparticles inside living cells.
The second approach uses more complex nucleic acid templates, such as DNA or RNA nanostructures, to control size, shape, and addressability of two- or three-dimensional protein assemblies. The shape of the final protein assembly reflects the shape of the templating nucleic acid nanostructure, and the protein assembly can be viewed as a coating that adds rigidity, stability, and, crucially, biological functionality to the template nanostructure. Both approaches one and two are amenable to library-scale screening by coupling size and shape of the particles as well as patterning of functional domains (“phenotype”) to the sequence of the nucleic acid template (“genotype”).
In a third approach, the nucleic acid is not incorporated into the final assembly, but merely serves as a “mold” to define size and composition of a protein assembly. A single DNA origami mold could thus “catalyze” the assembly of many nanoparticles, circumventing potential scalability bottlenecks from approach two.
These assemblies use the synergy between DNA nanotechnology and protein design to achieve properties that would not be accessible to either technology alone.

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Topic(s)

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Call for proposal

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(opens in new window) ERC-2023-STG

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Host institution

INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
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.

€ 1 499 711,00
Address
Am Campus 1
3400 KLOSTERNEUBURG
Austria

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Region
Ostösterreich Niederösterreich Wiener Umland/Nordteil
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.

€ 1 499 711,00

Beneficiaries (1)

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