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PhosFunc SIGNED

Dissecting the functional importance of eukaryotic protein phosphorylation

Total Cost €

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EC-Contrib. €

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Partnership

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 PhosFunc project word cloud

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

grouped    fungal    cerevisiae    routinely    sense    fraction    phosphoproteomic    phosphosites    dissecting    train    created    mutants    instrumental    shown    predictors    age    biological    thousands    diverge    mutagenesis    fitness    disrupt    evolution    relevance    proteins    conditional    natural    cues    reveal    modifications    pleiotropy    mass    improvements    modulates    library    regulation    18    world    yeast    stress    cells    subset    groupings    events    ascomycota    initial    lastly    post    libraries    translational    phosphorylatable    proteome    mechanisms    interactions    spectrometry    gene    phospho    predicted    ptm    functional    phosphorylation    point    function    ptms    functionally    systematic    abundant    evolutionary    datasets    environmental    genetic    cell    mutations    isolates    classifier    history    genomes    knock    sites    reconstruct    intricate    signaling    extant    trained    diverse    populations    protein    species    manner    unveiling   

Project "PhosFunc" data sheet

The following table provides information about the project.

Coordinator
EUROPEAN MOLECULAR BIOLOGY LABORATORY 

Organization address
address: Meyerhofstrasse 1
city: HEIDELBERG
postcode: 69117
website: http://www.embl.de

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 Germany [DE]
 Total cost 1˙451˙421 €
 EC max contribution 1˙451˙421 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-04-01   to  2020-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EUROPEAN MOLECULAR BIOLOGY LABORATORY DE (HEIDELBERG) coordinator 1˙451˙421.00

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 Project objective

Cells have evolved intricate systems to sense environmental changes and an initial response to such cues is often driven by post-translational modifications (PTMs) of proteins. Protein phosphorylation is an abundant PTM that modulates protein function via diverse mechanisms. Improvements in mass-spectrometry are unveiling a complex world of PTM regulation with thousands of phosphosites routinely identified per study. We and others have recently shown that phosphosites can diverge quickly during evolution and that a significant fraction may have no biological role in extant species. Identifying functionally relevant phosphosites is therefore a major challenge in cell-signaling. In the past, gene knock-out libraries and genetic methods have been instrumental in dissecting gene-function in a systematic manner. Here, we aim to develop genetic approaches to study the functional relevance of phosphorylation in S. cerevisiae. Phosphoproteomic datasets for 18 ascomycota fungal species will be used to reconstruct the evolutionary history of phosphorylation events in these species. S. cerevisiae sites will then be grouped according to age and predicted function (e.g. regulation of interactions, activities, etc) and a subset will be selected for mutagenesis. A library of non-phosphorylatable point mutants will be created and used to measure fitness under different stress conditions. These will reveal the functional importance, pleiotropy and relevant pathways of the selected phosphosites. The age, functional groupings and the genetic information will allow us to train predictors of the conditional fitness of phosphosites at proteome-wide level. Lastly, we will study the importance of evolutionary changes in phospho-regulation in natural populations of yeast. Mutations that likely disrupt phosphosites will be identified from the genomes of natural isolates and the consequences of these mutations will be predicted based on the trained classifier.

 Publications

year authors and title journal last update
List of publications.
2016 David Ochoa, Mindaugas Jonikas, Robert T Lawrence, Bachir El Debs, Joel Selkrig, Athanasios Typas, Judit Villén, Silvia DM Santos, Pedro Beltrao
An atlas of human kinase regulation
published pages: 888, ISSN: 1744-4292, DOI: 10.15252/msb.20167295
Molecular Systems Biology 12/12 2020-04-22
2016 Omar Wagih, Naoyuki Sugiyama, Yasushi Ishihama, Pedro Beltrao
Uncovering Phosphorylation-Based Specificities through Functional Interaction Networks
published pages: 236-245, ISSN: 1535-9476, DOI: 10.1074/mcp.M115.052357
Molecular & Cellular Proteomics 15/1 2020-04-22
2019 Marta J. Strumillo, Michaela Oplová, Cristina Viéitez, David Ochoa, Mohammed Shahraz, Bede P. Busby, Richelle Sopko, Romain A. Studer, Norbert Perrimon, Vikram G. Panse, Pedro Beltrao
Conserved phosphorylation hotspots in eukaryotic protein domain families
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-09952-x
Nature Communications 10/1 2020-04-22
2015 Marta Strumillo, Pedro Beltrao
Towards the computational design of protein post-translational regulation
published pages: 2877-2882, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2015.04.056
Bioorganic & Medicinal Chemistry 23/12 2020-04-22
2016 R. A. Studer, R. A. Rodriguez-Mias, K. M. Haas, J. I. Hsu, C. Vieitez, C. Sole, D. L. Swaney, L. B. Stanford, I. Liachko, R. Bottcher, M. J. Dunham, E. de Nadal, F. Posas, P. Beltrao, J. Villen
Evolution of protein phosphorylation across 18 fungal species
published pages: 229-232, ISSN: 0036-8075, DOI: 10.1126/science.aaf2144
Science 354/6309 2020-04-22

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