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MHCIbiopic SIGNED

MHC-I biogenesis and degradation at the endoplasmic reticulum membrane

Total Cost €

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EC-Contrib. €

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Partnership

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 MHCIbiopic project word cloud

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

microbial    one    trigger    mass    viruses    extend    protein    complexes    cytomegalovirus    stabilized    proteins    eukaryotic    combine    transiently    reticulum    oligomeric    tomography    largely    integrative    critical    chaperones    researcher    membrane    association    start    hcmv    picture    situ    vitro    cells    career    leader    exported    degradation    model    larger    possibly    light    heavy    mhc    electron    cell    cryo    assembly    calnexin    spectrometry    free    insertion    cellular    hetero    peptide    microsomal    us11    trimeric    us2    ms    secretory    cet    utilizes    assembles    membranes    proteostasis    human    contributions    scales    cross    basic    cd8    independent    tapasin    immunoevasins    blooming    functional    translocation    formed    assisted    co    histocompatibility    proteome    data    nascent    viral    erad    erp57    surface    stress    tumors    immune    biogenesis    endoplasmic    scientific    mechanism    once    community    lack    loaded    length    opportunity    er    structural    ray    translationally    xl    entrance    network    crystallography    substrate    assemblies    recognition    assays    unravel    maturation    folding    chain    molecular    ultimately    diseases    linking   

Project "MHCIbiopic" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITEIT UTRECHT 

Organization address
address: HEIDELBERGLAAN 8
city: UTRECHT
postcode: 3584 CS
website: www.uu.nl

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 Netherlands [NL]
 Total cost 165˙598 €
 EC max contribution 165˙598 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-02-01   to  2021-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITEIT UTRECHT NL (UTRECHT) coordinator 165˙598.00

Map

 Project objective

One third of the cell proteome utilizes the secretory pathway for entrance into the endoplasmic reticulum (ER). However, the insertion of nascent proteins into or their translocation across the ER membrane, their maturation and assembly to oligomeric complexes and their degradation are very basic cellular processes of which we largely lack an integrative structural insight. I propose to use Cryo Electron Tomography (CET) to unravel the molecular mechanism of the biogenesis and degradation of Major Histocompatibility Complex-I (MHC-I) as a model substrate in situ. MHC-I are critical for immune responses to viruses and tumors. They are hetero-trimeric complexes formed by a light chain, a heavy chain and a variable cellular or microbial peptide. MHC-I folding is assisted by the chaperones ERp57 and calnexin at the ER membrane, where it assembles co-translationally, stabilized by tapasin. Once loaded with a peptide, MHC-I is exported to the cell surface for recognition by CD8 T-cells. However, some viral immunoevasins like the human cytomegalovirus (HCMV) proteins US2 and US11 trigger the ER-Associated Degradation (ERAD) of MHC-I. I will combine data from CET, cross linking mass spectrometry (XL-MS) and in vitro functional assays on eukaryotic cellular and microsomal cell-free systems to provide an integrated picture of the complexes transiently involved in these processes. This work will make great contributions to our molecular understanding of cellular proteostasis and possibly provide novel molecular targets addressing diseases associated with ER stress. The proposed project will extend my knowledge from protein X-ray crystallography to the study of more complex molecular assemblies in association with membranes at larger length scales – ultimately the cell. Taken together, this project represents a unique opportunity to start blooming in my career as an independent researcher with a strong european network, and become a leader in the scientific community.

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

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