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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.

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

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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