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Establishing genetic code expansion as a tool to study neuronal circuit function in an animal

Objective

We pioneered technologies that allow the site-specific introduction of chemically synthesized unnatural amino acids (UAA) into a chosen protein within the context of a multicellular organism - the nematode worm C. elegans. The foundational technology for this advance is genetic code expansion.
In its most simple form, genetic code expansion to incorporate UAA into proteins requires an orthogonal aminoacyl-tRNA synthetase/tRNACUA pair to be introduced into the host organism. The orthogonal aminoacyl-tRNA synthetase must specifically recognize an UAA and use this amino acid to specifically aminoacylate its cognate orthogonal tRNACUA, which is itself not a substrate for endogenous synthetases. The aminoacylated tRNA then decodes an amber stop codon introduced into a gene of interest at a specific site.
Our proposal is at the intersection of synthetic multicellular biology and organismal neurobiology. We aim to engineer photo-activateable proteins in C. elegans neurons by site specifically incorporating photo-caged unnatural amino acids. This will allow us to develop tools to: i) control within an intact, freely moving animal the activity of any desired single neuron or group of neurons, and ii) eventually control the chemical and electrical synaptic connectivity between neurons. We will then apply this technology to investigate how neuronal circuits generate behaviour.
In addition and complementary to the development and application of neurobiological tools we will further improve the coding capacity of the worm’s protein synthesis machinery.

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Topic(s)

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2015-STG

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Host institution

THE UNIVERSITY OF EDINBURGH
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.

€ 1 499 520,00
Address
OLD COLLEGE, SOUTH BRIDGE
EH8 9YL Edinburgh
United Kingdom

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Region
Scotland Eastern Scotland Edinburgh
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.

€ 1 499 520,00

Beneficiaries (1)

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