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Non-covalent photoresponsive tags for photoacoustic imaging: Giving voice to living matter

Project description

From colour to sound, novel probes focus on protein targets of interest

Proteins are ubiquitous, and the ability to visually trace their pathways, modifications, abundance and activities is critical to our understanding of living organisms. Photoacoustic imaging (PAI) is a non-invasive and non-ionising imaging modality of high resolution and high sensitivity, even at large imaging depths. It is based on the detection of light-induced ultrasound waves from the excitation of chromophores, molecules that absorb certain wavelengths of visible light and thus confer colour. The EU-funded SmartSAST project is enhancing the performance and utility of promising PAI technology with very high-specificity probes that simultaneously produce very high contrast and enable the study of multicomponent living systems. Novel photoacoustic probes will both tag proteins of interest and non-covalently bind photoresponsive organic chromophores, resulting in very high resolution imaging of specific protein targets.

Objective

Visualizing the complexity of living matter non-invasively and with high-resolution represents an indispensable element for progress in science. Unresolved issues as the individuation of early-stage cancers, or the spatial organization of the roots microbiomes, can benefit from advancements in photoacoustic imaging (PAI). This appealing technology combines the benefits of light as input and ultrasounds as output, offering a compelling combination of good resolution, high penetration depth, and non-invasiveness.
However, PAI is not suitable to study multicomponent living systems because current strategies operate with simple probe-detector setups. With SmartSAST (Smart Sound-activated Absorption Shifting Tags), I propose to enable modularity and multiplexing through the development of photoacoustic probes based on protein tags that non-covalently bind with photoresponsive organic chromophores named sonogens. The supramolecular nature of SmartSAST ensures great modularity as the sonogens can be easily refreshed or substituted. The change in optical properties of the probes upon assembly guarantees great contrast against the background. Finally, via rationally designing photo-isomerizable sonogens that bind the protein just in a specific isomeric form, SmartSAST imparts an unprecedented level of control in PAI. Upon photo-modulating the supramolecular dynamics of these probes and extracting their kinetic signatures, dynamic contrast and multiplexing will be achieved with high spatial resolution.
SmartSAST project aims to develop a fully operative technology based on new fundamentals bases. The project includes the synthesis of sonogens, the engineering of protein tags, the thermokinetic and photochemical characterization of the probes and their application in PAI. This new approach to PAI will unlock the non-invasive study of deeply embedded complex biological targets in real-time. Dissemination and communication activities will secure the great impact of SmartSAST.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

ECOLE NORMALE SUPERIEURE
Net EU contribution
€ 184 707,84
Address
45, RUE D'ULM
75230 Paris
France
Region
Ile-de-France Ile-de-France Paris
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 184 707,84