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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.

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

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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