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RiboStress

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Stress-induced structural and organizational adaptations of the cellular transla...

Stress-induced structural and organizational adaptations of the cellular translation machinery Many cellular and extracellular events cause perturbations of protein homeostasis by affecting either de novo protein folding or by destabilizing already folded proteins. Under such proteotoxic stress conditions, cells engage in v... ver más

31/12/2027

UHEI

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

RUPRECHTKARLSUNIVERSITAET HEIDELBERG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-01-01

ERC-2022-STG: ERC STARTING GRANTS Scope:Objectives

I+D

Cerrada hace 3 años

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Duración del proyecto: 59 meses Fecha Inicio: 2023-01-01
Fecha Fin: 2027-12-31

Líder del proyecto

RUPRECHTKARLSUNIVERSITAET HEIDELBERG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Many cellular and extracellular events cause perturbations of protein homeostasis by affecting either de novo protein folding or by destabilizing already folded proteins. Under such proteotoxic stress conditions, cells engage in various strategies to avoid further damage to the cellular proteome, e.g. by timely modulation of translation activity and specificity, or by resolving the underlying events. Our overall goal is to dissect from a unique structural angle how such damage avoidance strategies impact on the structure and molecular organization of the translation machinery by directly imaging their effects on ribosome structure, supramolecular organization and distribution in a cellular context with cryo-electron tomography (cryo-ET), an innovative imaging approach unique in its capability to pro-vide highly detailed three-dimensional structural information on macromolecular complexes in their cellular environment. Building on my pioneering work in the field of cryo-ET and integrating novel image processing solutions that have recently marked a breakthrough in the field, we will dissect at unprecedented resolution how the cellular translation machinery is remodeled i) after a general heat-shock, ii) during the Endoplasmic Reticulum unfolded protein response and iii) during persistent translational stalling triggering ribosome-associated quality control.Work included in this proposal will provide detailed structural and mechanistic insights into how cells try to counteract an imbalance of protein homeostasis - a hallmark of neurodegenerative diseases. It thus seems almost certain that key concepts emerging from our studies will have direct implications on mechanistic understanding of central pathological principles underlying these diseases.

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