Record #197750 - GSI Repository

GeneREFORM

Genetically Encoded Multicolor Reporter Systems For Multiplexed MRI

Coordinator	Weizmann Institute of Science
Grant period	2016-05-01 - 2021-04-30
Funding body	European Union
Call number	ERC-2015-STG
Grant number	677715
Identifier	G:(EU-Grant)677715

Note: 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.

Recent Publications

There are no publications

Record created 2016-11-19, last modified 2023-02-14

Similar records

Add to personal basket
Export as Author List with IDs BibTeX (UTF-8), EndNote XML, EndNote Text, RIS, MARC, Print MARC, MARCXML, DC,
Request correction
Submit fulltext

GSI Homepage \| GSI Library \| English Deutsch \| guest :: login GSI Repository
Search	Submit	Personalize Your alerts Your baskets Your searches	Help