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PhosFunc SIGNED

Dissecting the functional importance of eukaryotic protein phosphorylation

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

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.

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

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 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.	DE (HEIDELBERG)	coordinator	1˙451˙421.00

Map

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

List of publications.
year	authors and title	journal	last update
2016	David Ochoa, Mindaugas Jonikas, Robert T Lawrence, Bachir El Debs, Joel Selkrig, Athanasios Typas, Judit VillÃ©n, 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 OplovÃ¡, Cristina ViÃ©itez, 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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