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APOSITE SIGNED

Apoptotic foci: composition, structure and dynamics

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 APOSITE project word cloud

Explore the words cloud of the APOSITE project. It provides you a very rough idea of what is the project "APOSITE" about.

coupled    combining    composition    dependent    organization    mitochondrial    molecular    stoichiometry    apoptotic    electron    macromolecular    plays    extraction    function    progression    mass    framework    question    clinical    inflammatory    mechanisms    bak    disease    tissue    contribution    immune    medicine    immunogenicity    imaging    mediate    assembly    foci    bax    labeling    single    avenues    biology    understand    ring    cutting    fluorescence    action    gap    deregulated    arc    pipeline    architecture    spatiotemporal    missing    aposite    reveals    correlate    situ    inflammation    proximity    unravel    modulators    ultimately    membrane    assemblies    edge    offers    outer    machineries    near    knowing    dynamics    live    organelle    structure    fundamental    microscopies    momp    form    apoptosis    chances    textbook    outcome    expertise    orchestrate    mediating    native    analytical    permeabilization    homeostasis    structural    multidisciplinary    central    building    death    cell    molecule    complexes    dimers    spectrometry    line   

Project "APOSITE" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAET ZU KOELN 

Organization address
address: ALBERTUS MAGNUS PLATZ
city: KOELN
postcode: 50931
website: www.uni-koeln.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-COG
 Funding Scheme ERC-COG
 Starting year 2019
 Duration (year-month-day) from 2019-04-01   to  2024-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAET ZU KOELN DE (KOELN) coordinator 1˙910˙421.00
2    EBERHARD KARLS UNIVERSITAET TUEBINGEN DE (TUEBINGEN) participant 89˙578.00

Map

 Project objective

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.

 Publications

year authors and title journal last update
List of publications.
2019 Flores-Romero, García-Sáez
The Incomplete Puzzle of the BCL2 Proteins
published pages: 1176, ISSN: 2073-4409, DOI: 10.3390/cells8101176
Cells 8/10 2020-03-11

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The information about "APOSITE" are provided by the European Opendata Portal: CORDIS opendata.

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