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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.

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

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

Leaflet | Map data © OpenStreetMap contributors, CC-BY-SA, Imagery © Mapbox

 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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