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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.

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

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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