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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.

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

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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