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Molecular Shape Microscopy

Objective

"Understanding how proteins work in living cells is one of biology's great challenges. Fluorescence technologies are compatible studies on living cells, but studying protein structures on the single-digit nanometre range severely restricts the time resolution, typically to that of fixed-cell experiments. Moreover, as most proteins are complex multi-domain machines, to truly understand their biological function, we need more than imaging of their position; we need to visualise their actual conformation, i.e. their 3D structure and dynamics and how their shape changes throughout their molecular activity.
This proposal introduces Molecular Shape Microscopy (MShapeM), designed to achieve real-time nanometre-resolution imaging of protein conformational dynamics inside the living cell. MShapeM is not a single technology, but integrates synergistic advances in three cutting-edge domains: (1) protein and RNA bioengineering using RNA trans-splicing and editing to reprogram multiple codons to incorporate several small fluorescent dyes with amino-acid precision into endogenous proteins; (2) innovative dye chemistry for developing dual-fluorogenic dyes for high signal-to-noise live-cell imaging; and (3) advanced scattering microscopy, to continuously track multiple stably emitting dyes at very high temporal and nanometre spatial resolution. Benchmark applications include the study of highly dynamic large proteins for which conformational dynamics are critical but poorly understood and not accessible with any other technology. By capturing ""molecular action movies"" of proteins at work, MShapeM will blend the boundaries between structural and live-cell imaging, affording unprecedented visual acuity on protein function in its native environment.

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Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2025-ADG

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Host institution

JOHANNES GUTENBERG-UNIVERSITAT MAINZ
Net EU contribution
€ 2 995 973,00
Address
SAARSTRASSE 21
55122 Mainz
Germany
Region
Rheinland-Pfalz Rheinhessen-Pfalz Mainz, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost
No data

Beneficiaries (1)