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DIAL-IN SIGNED

Dynamic Integrated structural and proteomic Analysis of the LUBAC complex and its involvement in NF-κB and inflammation

Total Cost €

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EC-Contrib. €

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Partnership

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 DIAL-IN project word cloud

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

player    one    clinical    xl    function    combining    ap    structure    repercussions    ligase    relevance    modular    kappa    poorly    dynamic    paradigm    em    first    molecular    swath    acquired    linking    give    mediate    pathogenesis    notably    critical    post    data    systemic    validation    ptms    cryo    ms    protein    translation    global    biological    proteomic    mass    canonical    organization    scenarios    purification    landscape    laboratory    integrate    expertise    cross    regulation    map    workflow    modules    transition    spectrometry    mechanistic    implications    line    phd    coupled    electron    fundamental    atomic    host    biomedical    clinically    genotype    components    assembly    medical    chain    dynamically    microscopy    regulated    inflammation    models    phenotypes    linear    modifications    output    biology    aebersold    of    ubiquitin    interactome    genomic    quantitative    forefront    lubac    affinity    mutants    variation    nf    technologies    phenotype    genetic   

Project "DIAL-IN" data sheet

The following table provides information about the project.

Coordinator
EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH 

Organization address
address: Raemistrasse 101
city: ZUERICH
postcode: 8092
website: https://www.ethz.ch/de.html

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 Switzerland [CH]
 Project website http://www.imsb.ethz.ch/research/aebersold/people/rodolfociuffa.html
 Total cost 175˙419 €
 EC max contribution 175˙419 € (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 2016-11-01   to  2019-03-02

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH CH (ZUERICH) coordinator 175˙419.00

Map

 Project objective

One of key challenges in current biology is to characterize the genotype to phenotype transition and explain how genomic variation results in specific phenotypes. According to the 'modular biology' paradigm, dynamically regulated multi-protein modules mediate this transition. My project aims at testing this paradigm by applying to a clinically highly relevant case study an integrated workflow of new technologies developed in the host laboratory. In particular, I will focus on a novel ubiquitin ligase complex, linear ubiquitin chain assembly complex (LUBAC), a critical but poorly understood player in several inflammation-related pathways, most notably the canonical NF-κB pathway. Given its key role in the pathogenesis of inflammation, understanding LUBAC will have fundamental biomedical implications. To investigate its structure, function and regulation, I will integrate data generated by mass spectrometry, which is the focus of the Aebersold laboratory, and cryo-electron microscopy (cryo-EM), which is the main expertise I acquired during my PhD. First, I will use quantitative affinity-purification coupled to mass spectrometry (AP-SWATH) to identify the dynamic interactome and the post-translation modifications (PTMs) of LUBAC. I will then define the structure of the complex by combining available atomic models of known LUBAC components, cryo-EM and cross-linking coupled to mass spectrometry (XL-MS). Finally, I will study clinical mutants and map the repercussions of genetic variation at the level of the complex organization, its interactome and of the global proteomic landscape. By these means, I will give a systemic and mechanistic account of the genotype to phenotype transition in clinically relevant scenarios. The output of the project, in line with the Work Programme, will be the production of new knowledge of fundamental biological and medical relevance and the development and validation of enabling technologies at the forefront of molecular biology research.

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