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Genetically Encoded Multicolor Reporter Systems For Multiplexed MRI

Objective

In order to fully understand the complexity of biological processes that are reflected by simultaneous occurrences of intra and inter-cellular events, multiplexed imaging platforms are needed. Fluorescent reporter genes, with their “multicolor” imaging capabilities, have revolutionized science and their founders have been awarded the Nobel Prize. Nevertheless, the light signal source of these reporters, which restricts their use in deep tissues and in large animals (and potentially in humans), calls for alternatives.
Reporter genes for MRI, although in their infancy, showed several exceptionalities, including the ability to longitudinal study the same subject with unlimited tissue penetration and to coregister information from reporter gene expression with high-resolution anatomical images. Inspired by the multicolor capabilities of optical reporter genes, this proposal aims to develop, optimize, and implement genetically engineered reporter systems for MRI with artificial “multicolor” characteristics. Capitalizing on (i) the Chemical Exchange Saturation Transfer (CEST)-MRI contrast mechanism that allows the use of small bioorganic molecules as MRI sensors, (ii) the frequency encoding, color-like features of CEST, and on (iii) enzyme engineering procedures that allow the optimization of enzymatic activity for a desired substrate, a “multicolor” genetically encoded MRI reporter system is proposed.
By (a) synthesizing libraries of non-natural nucleosides (“reporter probes”) to generate artificially “colored” CEST contrast, and (b) performing directed evolution of deoxyribonucleoside kinase (dNK) enzymes (“reporter genes”) to phosphorylate those nucleosides, the “multicolor” genetically encoded MRI “reporter system” will be created. The orthogonally of the obtained pairs of substrate (CEST sensor)/ enzyme (mutant dNK) will allow their simultaneous use as a genetically encoded reporter system for in vivo “multicolor” monitoring of reporter gene expression with MRI.

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Topic(s)

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Funding Scheme

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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

WEIZMANN INSTITUTE OF SCIENCE
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.

€ 1 478 284,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

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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.

€ 1 478 284,00

Beneficiaries (1)

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