Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Development and application of global lipidomic arrays to inflammatory vascular disease. (LIPIDARRAY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: United Kingdom,United Kingdom
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-07-31
Duration (months): 66.0
Total project cost (EUR): 2969345.4
EU funding (EUR): 2969345.4
Participants: 2
Project status: CLOSED

How lipids are regulated on a global scale during vascular inflammation is not known. Thus, a major challenge exists to describe and catalog the total lipidome, in particular enabling the identification of new biologically active lipids, and description of changes. This is analogous to ‘omics’ of DNA, RNA and protein, but instead describing diversity of lipids in tissue samples. Importantly, this would encompass not only knowns, but also the vast number of unknowns that have not yet been catalogued in any study so far. Here, new systems biology approaches that can be applied to many other diseases or samples, and integrated with transcriptomic or proteomic analyses will be developed. These would be used to characterize the global lipidome during differentiation of immune cells, and in ex vivo samples from genomically-characterized inflammatory vascular disease. I hypothesize that development and application of “global lipidomic arrays” will define how lipids are regulated during vascular cell differentiation and inflammation, will identify new markers, and open up new therapeutic strategies. These aims go beyond the current state of the art, and will be achieved by the following objectives that include novel interdisciplinary concepts and approaches: 1. Develop analytical methodologies using Fourier transform mass spectrometry and bioinformatics. 2. Develop approaches for structural identification, using high resolution MSn, high sensitivity NMR, and new computational methodologies. 3. Define the size and diversity of the mammalian cellular lipidome in human platelets (validation). 4. Characterize the global lipidome in (i) monocytes during differentiation from stem /yolk cells to resident, inflammatory or foam cells, (ii) plasma from samples genomically characterized for 14 separate risk alleles for cardiovascular and Alzheimer’s disease. 5. Develop an open access web-based resource for storage and curation of the results to allow others to mine the data.

Keywords: alzheimer's disease,mass spectrometry,monocytes,macrophages,platelets,vascular,inflammation.
Principles of Protein Group Modification by the SUMO Pathway (SUMOGROUP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Germany
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2017-10-31
Duration (months): 45.0
Total project cost (EUR): 1403060.0
EU funding (EUR): 1403060.0
Participants: 1
Project status: CLOSED

Posttranslational modification (PTM) of proteins by ubiquitin family proteins is of fundamental importance for cellular function, regulation and development. Ubiquitylation typically targets individual proteins, and high selectivity is achieved by a plethora of ubiquitin-conjugating enzymes and ligases. Much less is known regarding how modification by the ubiquitin-related protein SUMO influences the function of substrates and how specificity is provided. Surprisingly, although SUMOylation affects roughly 10% of all yeast proteins, only very few enzymes participate in the pathway. Moreover, although SUMOylation is essential for viability, mutants defective in SUMOylation of individual substrates usually lack deleterious phenotypes. We recently solved this puzzle as we found that SUMOylation frequently targets protein groups (“protein group modification”) rather than individual substrates; single modifications are often redundant or additive as SUMO functions as intermolecular “glue”, thereby stabilizing protein complexes. Hence, the traditional view that a single PTM on a given protein mediates a specific function does not seem to apply for many SUMO modifications. Entirely divergent from previous approaches we will thus focus for the first time specifically on protein group SUMOylation and its special requirements for specificity, induction and termination. Initially found for proteins of homologous recombination and nucleotide excision DNA repair, we will expand the concept of protein group SUMOylation with a focus on pathways relevant for cellular regulation and which are of medical importance. We will define the substrate repertoire of SUMO ligases, characterize their substrate targeting properties, and design novel tools aimed to address the function of protein group SUMOylation. We expect that our work will finally put studies of this important modifier on a solid basis and will break new ground in areas of cellular regulation and cell biology in general.

Keywords: dna repair,nuclear function,substrate specificity
Labor Market Risk and Skill Diversity: Implications for Efficiency, Policy, and Estimation (RISK AND DIVERSITY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Individuals, institutions and markets
Countries involved: Spain,United Kingdom
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-05-01
End date: 2020-04-30
Duration (months): 72.0
Total project cost (EUR): 2116971.0
EU funding (EUR): 2116971.0
Participants: 2
Project status: CLOSED

Labor market risk and skill diversity are central features of the labor market. Arguably, employment risk is one of the biggest sources of uncertainty most individuals face in their life time. Likewise, exploiting the synergies and complementarities between differentially skilled workers is amongst the greatest challenges to firms' hiring decisions. The objective is to analyze the efficiency properties and as a consequence evaluate the role for policy. In order to establish the implications of the mechanisms that govern risk and diversity, I elaborate on concrete applications and discuss estimation in different labor market settings. In the presence of Labor Market Risk I address the question how asset holdings exacerbate wage inequality. Workers are exposed to the risk of unemployment, and workers with few assets will trade off the lower riskiness of a job against lower wages. Different asset holdings translate into different wages, thus amplifying inequality due to assets with wage inequality. The proposed analysis of unemployment risk can solve for an equilibrium model that incorporates the distribution of assets, while at the same time allowing for heterogeneity in skills. There is no doubt that fully understanding the asset-skill tradeoff is of primary importance for labor market policy. I then study a different angle of labor market risk, namely risk that is due to matching stochastic types, which introduces ex post mismatch. Ex ante, agents match based on the distribution of possible realizations of ex post types. This model is conducive to identification of complementarities between workers and the value of risk sharing. Skill Diversity, or the allocation of differentially skilled workers across firms of different productivity, is a central feature of the labor market. The aim of this research is to embed the optimal worker composition within firms into standard macro environments to study technological change, information aggregation and spatial diversity.
The origins of stellar properties (STELLARPROP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Universe sciences
Countries involved: United Kingdom
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-03-01
End date: 2019-08-31
Duration (months): 66.0
Total project cost (EUR): 1706418.0
EU funding (EUR): 1706418.0
Participants: 1
Project status: CLOSED

Less than a century ago it was realised that stars are still forming in our Galaxy today. Over the decades since, the questions of what physical processes dominate the star formation process and how the statistical properties of stars are determined have been some of the key questions in astrophysics. Recently, I have advanced numerical simulations of star formation to the point that, for the first time, we can reproduce a wide range of the observed statistical properties of stars and brown dwarfs. Here I propose an ambitious project that will make a step change in star formation theory and produce a truly predictive theory of star formation, as opposed to the past state of the field where we have been constantly searching for a mixture of initial conditions and physical processes that can reproduce the stellar properties that we observe. The project will involve substantial numerical code development, culminating in a fluid dynamical code that incorporates all of the major physical processes thought to influence star formation, including radiative transfer, non-ideal magnetohydrodynamics, dust, and chemistry. The scientific outputs will be the determination of how each physical process affects the star formation process, and a wide range of predictions of how stellar properties should vary in different environments and with different initial conditions. These predictions will give direction to, and be tested by, the next generation of observational surveys of star-forming regions and stellar systems, while at the same time may be employed to improve our understanding of how star formation affects galaxy formation and evolution and how the variation in stellar properties impacts the diversity of planetary systems.
Paratexts of the Bible. Analysis and Edition of the Greek Textual Transmission (PARATEXBIB)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Cultures and cultural production
Countries involved: Switzerland
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-10-01
End date: 2020-09-30
Duration (months): 72.0
Total project cost (EUR): 2496642.0
EU funding (EUR): 2496642.0
Participants: 2
Project status: CLOSED

This project takes a new look at an old text. The Bible is a fundamental book for the history of religious beliefs, cultural history, art history as well as many other fields. For centuries it has been read and copied multiple times. Thousands of medieval manuscripts survive. The process of transmission is considered here from a totally new perspective. While biblical manuscripts have so far been largely analysed as witnesses to an original text (“Urtext”), this project approaches each manuscript as a single witness to an act of reading and re-interpreting the text. In recent literary theory, attention has been drawn to “paratexts”, i.e. all material accompanying a main text. Virtually all biblical manuscripts have some of these features. Examples include brief introductions, biographies, tables of contents, poems, cross-references, prayers, and indexes. However, these paratexts have been neglected by scholars for two reasons: firstly because biblical studies traditionally concentrate on the “inspired text” itself; secondly because of the sheer amount of available material, which far exceeds the capacities of a single scholar. Moreover, being very short, these paratexts have often remained below the detection threshold, and since we are dealing with a rich and “liquid” transmission, many of them also present a methodological challenge. The project will therefore adopt a new approach. Firstly, it will catalogue all available material in an e Clavis, taking into account recent developments in the fields of structural codicology and digital technology. Secondly, it will develop a set of categories according to which each paratext of the New Testament will be edited according to internal criteria. This will be done with a view to the intrinsic value of each manuscript witness. The final result will be a comprehensive and totally new picture of the Biblical text’s “journey” through the centuries. This synthesis will be published as a monograph.
Patterns in Big Data: Methods, Applications and Implications (THINKBIG)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Computer science and informatics
Countries involved: United Kingdom
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-03-01
End date: 2020-02-29
Duration (months): 72.0
Total project cost (EUR): 2112798.0
EU funding (EUR): 2112798.0
Participants: 1
Project status: CLOSED

The availability of huge amounts of data has revolutionized many sectors of society, enabling engineers to bypass complex modeling steps, scientists to find shortcuts to new knowledge, and businesses to explore novel business models. For all its success, this field is still very young, and in need of systematic attention. Both risks and opportunities are very significant at this stage. They can be organized into three interconnected areas, which need to be addressed in a coordinated way: methods, applications and implications. By this we mean the interconnected needs to 1) develop new technology to take advantage of this resource; 2) explore the domains where this technology can make a significant impact; and 3) develop a set of cultural, legal and technical tools to reduce the risks associated with the application of these technologies to science and society. This project is about understanding, exploiting and managing the paradigm shift that is under way. It will address these three areas at the same time, 1) developing new types of algorithms and software architectures to take full advantage of this opportunity; 2) exploring new areas of opportunity for big-data to make an impact, with particular attention to the growing field of computational social sciences; and 3) investigating the ethical and epistemological challenges that arise from the transition towards a data-driven way of running society, business and science. We build on a strong track record in each of these areas. We have secured access to a valuable resource for historians, the collection of all UK newspapers from the past 200 years, which we will analyze with our tools, and we will greatly expand our current work on social media mining, working closely with colleagues from other disciplines. It is our intention to impact the social sciences, the general public and the law makers, besides our field of engineering.

Keywords: big data,computational scoial science,media content analysis,privacy,ethics,epistemology,science automation,artificial intelligence,data mining,data science,pattern recognition
New chemical biology for tailoring novel therapeutics (NCB-TNT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: United Kingdom,United Kingdom
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-03-01
End date: 2020-02-29
Duration (months): 72.0
Total project cost (EUR): 2499991.0
EU funding (EUR): 2499991.0
Participants: 3
Project status: CLOSED

Most of our drugs derive from natural products, many more natural products possess biological activity but our inability to synthesise novel analogues hampers our ability to use them either as tools or medicines. Cyclic peptides are common structural motifs in natural products and medicines (vancomycin, gramicidin). They are widely recognised to constitute a promising and still underexploited class of molecule for novel therapeutics; specifically an important role for cyclic peptides in the inhibition of protein-protein interactions has been demonstrated. We will harness the power of the recently identified macrocyclases from the ribosomally-derived cyanobactin superfamily to prepare diverse modified cyclic peptides. These enzymes exhibit the remarkable ability to macrocyclise unactivated peptide substrates. Different members of this family of macrocyclases process peptides into macrocycles containing from six up to twenty residues. We have characterised and re-engineered one member of the family (PatG) which makes eight residue macrocycles. We will determine the structural and biochemical features of the macrocyclases that are known to lead to six or to twenty residue macrocycles. We will use these insights to put these enzymes to work in novel chemical reactions. We will combine macrocyclases with other enzymes from the cyanobactin biosynthetic pathways (whose structures and mechanism we have largely determined) and work on solid phase peptide substrates. By bringing together the power of solid phase methods (split and pool) and the novel chemistry enabled by the enzymes, we will generate highly diverse macrocyclic scaffolds containing amino acids, enzymatically modified amino acids, non-natural amino acids and non-amino acid building blocks. Successful completion of the project will revolutionise the design of cyclic peptide-inspired libraries with diverse backbone scaffolds for applications in target identification, drug discovery and tool screening.

Keywords: chemical biology,enzyme mechanism
HOMEOSIGN : Homeoprotein signaling during development and in the adult (HOMEOSIGN)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: France
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-03-01
End date: 2019-02-28
Duration (months): 60.0
Total project cost (EUR): 2499995.0
EU funding (EUR): 2499995.0
Participants: 1
Project status: CLOSED

Homeoprotein (HP) signaling designates the ability of HP transcription factors to transfer between cells, thus acting as signaling molecules. We will investigate several properties of this novel signaling pathway in the CNS and how it can shed light on brain development and physiology, also neurological and psychiatric pathologies. The studies will concentrate on 4 HPs (Engrailed1/2, Otx2 and Pax6) illustrative of the HP family and of high physiological interest. Mouse lines will be developed in which the extracellular expression of single chain antibodies against these HPs can be induced at specific places and times, allowing us to follow the consequences of neutralizing extracellular HPs while preserving their cell autonomous functions. With this tool (and others) we shall study if (and how) HP transfer regulates boundary position in the neuroepithelium and direct cell/axon migration and guidance. In postnatal development, we will dissect how Otx2 regulates the opening, closure and reopening of critical periods in the cortex and controls the behavior of neuronal networks throughout life. Also in the adult we will follow how HPs regulate the physiology and survival of distinct neuronal groups, including midbrain dopaminergic neurons. We shall analyze the physiological interactions between HPs and classical signaling molecules and identify HP targets, in particular those regulating the cell energy metabolism, and explore their ability to modulate the epigenetic state of the chromatin. Using Otx2 and Engrailed as baits, we shall identify the complex sugars with which they interact at the cell surface to get an entry into the "sugar code" that confers specificity to HP capture by distinct cell populations. This project should identify new HP functions and highlight them as part of a major mode of signal transduction in the developing and mature CNS. It is expected that this will modify the way we look at many developmental, evolutionary and physiological mechanisms.

Keywords: homeoproteins,signaling,critical periods,compartmentalization,guidance,mitochondria
Regulatory transcriptional networks orchestrating mouse pluripotent embryonic stem cells (SYSSTEMCELL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: Netherlands
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-03-01
End date: 2019-02-28
Duration (months): 60.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

The lack of a quantitative framework around the dynamics of gene expression and its determinants represents a major hurdle for capturing transcription regulation into regulatory models. Embryonic Stem Cells (ESC) provide an excellent cellular model to quantitatively define the principles of gene regulation at the biochemical and (epi)genetic level. In SysStemCell, I will focus on two distinct mouse pluripotent cell states. My recent studies have shown that the epigenome and transcriptome of ESCs maintained in serum-free medium complemented with two kinase inhibitors and LIF (‘2i ESC’) are distinct from classical ESCs cultured in the presence of serum and LIF (‘serum ESC’). Importantly, the 2i ESCs reflect pre-implantation stage ICM cells whereas the widely studied serum cells reflect post-implantation ESCs. These two distinct pluripotent states are interconvertible in vitro, providing an unique and accessible model to explore the regulation of the pre- to post-implantation phase of early embryonic development. I will combine state-of-the-art proteomics and chromatin-based methods, including a novel in vivo UV femtosecond laser crosslinking approach, and in depths bioinformatics in an iterative manner to define the full compendium of transcription (co)factors (TF) and TF-modules that define the two cell states. The dynamics of long- and short-range interactions between these modules will be assessed and correlated with the epigenetic state and chromatin structure. Novel and existing factors will be assessed for their role in differentiation from 2i to serum and reverse programming using knockout and forced expression strategies. Collectively, my studies will provide an invaluable resource for the community and a deep insight in the mechanisms and general principles that orchestrate gene expression in particular in the hitherto unexplored transition at implantation during early mouse development.

Keywords: transcription factor networks,embryonic stem cells,genomic interactions