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DynOMIS

Dynamic Origins of MHC class I Selector function

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 DynOMIS project word cloud

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

transformations    class    healthy    context    molecules    adaptive    cell    industrial    sophisticated    interdisciplinary    investigation    selecting    mechanisms    peptides    histocompatibility    elucidate    dynamics    mediator    unleash    surface    basis    chemists    energy    predict    epitopes    stratify    biochemical    exact    equally    employ    infectious    interactions    immunity    dynomis    deep    immune    peptide    structure    bound    antigen    fundamental    world    quantitative    infections    lymphocytes    proteins    apparatus    simulations    cancer    mhc    mechanism    suitability    malignant    timescales    free    biologists    antigenic    cytotoxic    group    secretory    calculations    clinically    thermodynamic    arsenal    immunological    molecular    researcher    biomarkers    vaccination    environment    patients    integrates    immunoprotective    pathogens    computational    cellular    vaccines    immunotherapy    function    cofactors    drive    comprising    turn    immunologists    structural    pave    experimental   

Project "DynOMIS" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY OF SOUTHAMPTON 

Organization address
address: Highfield
city: SOUTHAMPTON
postcode: SO17 1BJ
website: http://www.southampton.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
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 Coordinator Country United Kingdom [UK]
 Project website https://www.researchgate.net/project/DynOMIS-Dynamic-Origins-of-MHC-class-I-Selector-function
 Total cost 195˙454 €
 EC max contribution 195˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-09-06   to  2018-09-05

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF SOUTHAMPTON UK (SOUTHAMPTON) coordinator 195˙454.00

Map

 Project objective

DynOMIS aims to elucidate the antigen selection mechanisms of the adaptive immune system at the molecular level in the highly complex cellular environment. Major histocompatibility complex class I molecules (MHC-I) is a key mediator of adaptive immunity, the cell’s arsenal against infectious pathogens and malignant transformations. MHC-I present antigenic peptides to cytotoxic T lymphocytes at the cell surface, which in turn unleash their cytotoxic apparatus only when peptides from non-healthy proteins are recognized. This process is the result of an equally important peptide selecting function in the early secretory pathway, a mechanism that has not been clearly understood in spite of its fundamental role in vaccination. Deep understanding of the exact mechanisms that drive peptide selection by MHC-I will help to predict immunoprotective epitopes in infections and cancer, which will in turn pave the way for the development of more effective T cell-targeting vaccines and biomarkers to stratify patients’ suitability for immunotherapy. DynOMIS will employ a sophisticated, interdisciplinary approach that integrates quantitative computational systems modelling to identify molecular mechanism from cellular biochemical information, experimental investigation of the structure and dynamics of peptide-bound MHC-I over a large range of timescales, and state-of-the-art molecular dynamics simulations and free energy calculations to elucidate the thermodynamic basis of the peptide selection mechanism in the context of their interactions with cellular cofactors. To this end, DynOMIS will be carried out by an experienced researcher at a world-leading interdisciplinary group comprising molecular immunologists, structural biologists, computational chemists, and industrial partners with a strong focus on clinically relevant immunological research.

 Publications

year authors and title journal last update
List of publications.
2017 Athanasios Papakyriakou, Efstratios Stratikos
The Role of Conformational Dynamics in Antigen Trimming by Intracellular Aminopeptidases
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2017.00946
Frontiers in Immunology 8 2019-06-13
2018 Athanasios Papakyriakou, Emma Reeves, Mary Beton, Halina Mikolajek, Leon Douglas, Grace Cooper, Tim Elliott, Jörn M. Werner, Edward James
The partial dissociation of MHC class I–bound peptides exposes their N terminus to trimming by endoplasmic reticulum aminopeptidase 1
published pages: 7538-7548, ISSN: 0021-9258, DOI: 10.1074/jbc.RA117.000313
Journal of Biological Chemistry 293/20 2019-05-09

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