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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.

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

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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