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APOSITE

Financiado

Apoptotic foci composition structure and dynamics

Apoptotic cell death is essential for development, immune function or tissue homeostasis, and it is often deregulated in disease. Mitochondrial outer membrane permeabilization (MOMP) is central for apoptosis execution and plays a... ver más

30/09/2025

UNIVERSITAT ZU KOL...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

UNIVERSITAT ZU KOLN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 3 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2019-02-18

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2018-COG: ERC Consolidator Grant

I+D

Cerrada hace 6 años

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3 Participantes

UNIVERSITAT ZU KOLN

1.91M€ | Lider

INDUSTRIAL ZOOTECNICA ARAGON...

551.36K€ | Participante

89.58K€ | Participante

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Duración del proyecto: 79 meses Fecha Inicio: 2019-02-18
Fecha Fin: 2025-09-30

Líder del proyecto

UNIVERSITAT ZU KOLN

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Apoptotic cell death is essential for development, immune function or tissue homeostasis, and it is often deregulated in disease. Mitochondrial outer membrane permeabilization (MOMP) is central for apoptosis execution and plays a key role in its inflammatory outcome. Knowing the architecture of the macromolecular machineries mediating MOMP is crucial for understanding their function and for the clinical use of apoptosis. Our recent work reveals that Bax and Bak dimers form distinct line, arc and ring assemblies at specific apoptotic foci to mediate MOMP. However, the molecular structure and mechanisms controlling the spatiotemporal formation and range of action of the apoptotic foci are missing. To address this fundamental gap in our knowledge, we aim to unravel the composition, dynamics and structure of apoptotic foci and to understand how they are integrated to orchestrate function. We will reach this goal by building on our expertise in cell death and cutting-edge imaging and by developing a new analytical pipeline to: 1) Identify the composition of apoptotic foci using in situ proximity-dependent labeling and extraction of near-native Bax/Bak membrane complexes coupled to mass spectrometry. 2) Define their contribution to apoptosis and its immunogenicity and establish their assembly dynamics to correlate it with apoptosis progression by live cell imaging. 3) Determine the stoichiometry and structural organization of the apoptotic foci by combining single molecule fluorescence and advanced electron microscopies. This multidisciplinary approach offers high chances to solve the long-standing question of how Bax and Bak mediate MOMP. APOSITE will provide textbook knowledge of the mitochondrial contribution to cell death and inflammation. The implementation of this new analytical framework will open novel research avenues in membrane and organelle biology. Ultimately, understanding of Bax and Bak structure/function will help develop apoptosis modulators for medicine.

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