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4D-BioSTEM

Financiado

Cerrado

4D scanning transmission electron microscopy for structural biology

Electron Microscopy (EM) has transformed research in the Life and Physical Sciences separately. Cryo-EM in Life Sciences allows the 3D structure determination of proteins down to 1.0 Å resolution in case they are large enough and... ver más

31/12/2029

FZJ

7M€

Presupuesto del proyecto: 7M€

Líder del proyecto

FORSCHUNGSZENTRUM JULICH GMBH No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Ver 3 Participantes

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-11-14

ERC-2023-SyG: ERC Synergy Grants Objective:The aim is to provide support for a small group of two to four Principal Investigators to...

I+D

Cerrada hace 2 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

3 Participantes

FZJ

2.50M€ | Lider

LMU MUENCHEN

2.50M€ | Participante

EPFL

2.49M€ | Participante

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Duración del proyecto: 73 meses Fecha Inicio: 2023-11-14
Fecha Fin: 2029-12-31

Líder del proyecto

FORSCHUNGSZENTRUM JULICH GMBH No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 7M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Electron Microscopy (EM) has transformed research in the Life and Physical Sciences separately. Cryo-EM in Life Sciences allows the 3D structure determination of proteins down to 1.0 Å resolution in case they are large enough and present in high numbers in homogeneous states. For many molecules involved in diseases like neurodegeneration, however, structure determination is still severely hampered due to their insufficient contrast when imaged in vitreous ice or in their native cellular environment. To date, EM in the Physical Sciences generated utmost contrast for light atoms and established a resolution in the range of 0.2 Å limited only by thermal motion. This record was achieved by evolving scanning transmission EM (STEM) from a 2D to a 4D imaging technique combining imaging with diffraction. In this project, we will work out 4D-BioSTEM methodologies and develop a cryo-EM tool that maximizes contrast and resolution by bringing together EM groups from Life and Physical Sciences. 4D-STEM imaging of frozen biological specimens will be approached with unique and specialized hardware, theory and simulation, the development of microscope operation routines, and image reconstruction algorithms. In particular, we will acquire sparse 4D data using ultrafast detectors, employ methods for direct phasing (differential phase contrast, DPC) and establish advanced, so-called ptychographic, techniques to gain maximal signal from noisy 4D cryo-STEM data that are limited in their electron dose budget. We will make use of synergies between recently separated fields in order to make proteins smaller than 50 kDa amenable to structure elucidation. Furthermore, we will expand 4D-STEM to tomography, to obtain high-contrast 3D reconstructions from cellular samples, human brain tissue of neurodegenerative diseases, and vitrified organic energy materials. A new comprehensive structural imaging framework will be put forward and benchmarked as to its utility in Life and Physical Science applications of cryo-EM.

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