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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.

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

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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