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Beyond super-resolution: ultra-resolution imaging provides solutions for synapse physiology and brain pathology

Project description

Development of ultra-resolution imaging for brain synapse studies

Modern imaging technologies are unable to present the topology of proteins accurately as the best super-resolution tools’ limits are at 20–30 nm, which is several times more than the sizes of the individual proteins. The EU-funded ULTRARESOLUTION project aims to develop reliable ultra-resolution imaging with a true molecular resolution of 1–5 nm. The project will combine optics-based super-resolution technologies with the innovative physical expansion of the samples. This approach will be employed to decipher the functional organisation of key components in brain synapses. The final goal is to establish simple protocols to expand the application of ultra resolution to every biomedical laboratory.

Objective

Neurons contain hundreds of specialized proteins, whose topology reflects activity, plasticity and disease. Present imaging techniques are unable to present this topology accurately, since even the best super-resolution tools are limited to at least 20-30 nm, many times the size of individual proteins (~3-7 nm). To solve this problem, our ground-breaking objective is to develop reliable ultra-resolution imaging, with true molecular resolution of 1-5 nm. We will combine optics-based super-resolution with a recent innovation, pioneered by our team – physical expansion of the samples. Our efforts will be aided by several imaging tools we have generated, from super-resolution modalities to nano-affinity probes, which, thanks to their power and ease-of-use, are already employed by hundreds of research groups. We will apply ultra-resolution to reveal the functional organization of key components of the synapse, in health and disease. We will also develop protocols for brain pathology samples, for future use in medical diagnostics. Finally, we will establish simple protocols that will enable the application of ultra-resolution in every biomedical laboratory. Our multidisciplinary group, composed of a synapse physiologist (Rizzoli), a single-molecule imaging chemist (Sauer), and a physics and bio-engineering specialist (Boyden), is optimally placed to address this challenge. All PIs are also super-resolution specialists, with extensive expertise in stimulated emission depletion (STED), direct stochastic optical reconstruction microscopy (dSTORM) and expansion microscopy (ExM), respectively. The vast expertise required by this project implies that none of our groups could pursue it alone, and that no other groups, world-wide, could attempt it. Its successful implementation will provide: 1) imaging technology far beyond the state-of-the-art, which will prove transformative in many branches of biology; 2) solutions to multiple questions on synaptic and brain function.

Host institution

UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS
Net EU contribution
€ 3 078 736,00
Address
Robert-Koch-Strasse 40
37075 Goettingen
Germany

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Region
Niedersachsen Braunschweig Göttingen
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 3 078 736,00

Beneficiaries (3)