Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
COherent Xray source INferred from Electrons accelerated by Laser (COXINEL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Systems and communication engineering
Countries involved: France
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-01-01
End date: 2018-12-31
Duration (months): 60.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

Since the first laser discovery in 1960 and the first Free Electron Laser (FEL) in 1977, Linac based fourth generation light sources provide intense coherent fs pulses in the X-ray range for multidisciplinary investigations of matter. In parallel, Laser Wakefield Accelerator (LWFA) by using intense laser beams interacting with cm long plasmas can now provide high quality electron beams of very short bunches (few fs) with high peak currents (few kA). The so-called 5th generation light source aims at reducing the size and the cost of these FELs by replacing the linac by LWFA. Indeed, spontaneous emission from LWFA has already been observed, but the presently still rather large energy spread (1 %) and divergence (mrad) prevent from the FEL amplification. In 2012, two novel schemes in the transport proposed in the community, including my SOLEIL group, predict a laser gain increase by 3 or 4 orders of magnitudes. COXINEL aims at demonstrating the first lasing of an LWFA FEL and its detailed study in close interaction with future potential users. The key concept relies on an innovative electron beam longitudinal and transverse manipulation in the transport towards an undulator: a "demixing" chicane sorts the electrons in energy and reduces the spread from 1 % to a slice one of 0.1%, and the transverse density is maintained constant all along the undulator (supermatching). Simulations based on the performance of the 60 TW laser of the Laboratoire d’Optique Appliquée and existing undulators from SOLEIL suggest that the conditions for lasing are fulfilled. The SOLEIL environment also possesses the engineering fabrication capability for the actual realization of these theoretical ideas, with original undulators and innovative variable permanent compact magnets for the transport. COXINEL will enable to master in Europe advanced schemes scalable to shorter wavelengths and pulses, paving the way towards FEL light sources on laboratory size, for fs time resolved experiments.

Keywords: free electron laser,accelerator,laser wakefield accelerator,undulator,electron beam,synchrotron radiation
Phagosome functions and antigen cross presentation in primary dendritic cells. (DCBIOX)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: France
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-09-01
End date: 2019-08-31
Duration (months): 60.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

T cell cross priming (the initiation of CD8+ T cell responses to antigen that are not expressed by dendritic cells, DCs) requires the phagocytosis of antigens by DCs and their presentation on MHC class I molecules, a process referred to as “cross presentation”. Here, we propose a series of integrated approaches to address the most fundamental mechanisms of cross presentation and explore the use of this process for translational purposes in human cancer. This proposal will pursue three main objectives: 1) To analyze the mechanisms of control of antigen cross presentation and phagocytic functions in DCs. We will use genome wide screens and conditional KO mice, associated to quantitative assays for phagosomal functions and cross presentation, to investigate the molecular mechanisms of cross presentation in vitro and in vivo. 2) To study the epigenetic programing of cross presentation during the ontogeny of mouse DC subpopulations. We will define a “cross presentation gene signature” that will be validated by systematic gene silencing in vitro and we will analyze the epigenetic basis of control of cross presentation-related genes developing DCs. 3) To investigate the regulation of cross presentation in human primary DCs and to develop translational approaches in cancer. We will study cross presentation and phagosome functions in primary human DC subpopulations and its regulation by innate receptors for the development of original immunomodulation and vaccination strategies. We will explore the use of DCs cross presentation abilities in solid tumor infiltrating DCs and their use for prognosis in cancer. The results of this project will unravel fundamental mechanisms of phagocytosis and its control by innate signals in mice and humans. The proposal also aims at defining new possible strategies for cancer treatment and prognosis.

Keywords: dendritic cells,antigen presentation
Polycomb repressor interactions in relation to the mammalian epigenome. (PRIME)

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
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 2421394.0
EU funding (EUR): 2421394.0
Participants: 1
Project status: CLOSED

In mammals Polycomb group (PcG) repressors play a central role in maintaining cell type specific gene expression patterns in stem cells and through differentiation and development. Accordingly, deficiencies in the Polycomb system are important in disease, notably in several types of cancer. Although it is established that the effector function of PcG proteins is in large part attributable to intrinsic histone modification activities, the mechanisms that target PcG proteins to defined loci remain poorly understood. A number of different models have been proposed in order to account for PcG targeting to CpG islands at the promoters of target genes, the inactive X chromosome, and in defined circumstances, to pericentric constitutive heterochromatin. Our recent studies, and those of others, have highlighted that underlying chromatin state and DNA methylation play an important role, and based on this we have developed a general model that can account for PcG localisation at all target loci. The central aim of this proposal is to test the general model and to determine the mechanisms by which underlying chromatin states dictate PcG factor binding. In a series of integrated experiments we will define chromatin modifications on mononucleosomes purified from PcG target loci, determine the activity of major PcG complexes in vitro using nucleosome templates assembled with recombinant histones/histone variants bearing specific chromatin modifications, and, using a novel photo-cross-linking strategy, define, at the atomic level, interactions of PcG complexes with chromatin templates in vitro. Finally, based on our findings we will establish de novo PcG target sites in cells and/or disrupt preexisting PcG target sites. These studies will help to define the fundamental mechanisms that determine PcG protein targeting, and in addition will provide insight into misregulation of PcG proteins in disease.
Dissecting the mechanisms governing centriole formation (CENFOR)

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: Switzerland
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-04-01
End date: 2019-03-31
Duration (months): 60.0
Total project cost (EUR): 2499270.0
EU funding (EUR): 2499270.0
Participants: 1
Project status: CLOSED

Centrioles are critical for the formation of cilia, flagella and centrosomes, as well as for human health. The mechanisms governing centriole formation constitute a long-standing question in cell biology. We will pursue an innovative multidisciplinary research program to gain further insight into these mechanisms, using human cells, C. elegans and Trichonympha as model systems. This program is expected to also have a major impact by contributing a novel cell free assay to the field, thus paving the way towards making synthetic centrioles. Six specific aims will be pursued: 1) Deciphering HsSAS-6/STIL distribution and dynamics. We will use super-resolution microscopy, molecular counting, photoconversion and FCS to further characterize these two key components required for centriole formation in human cells. 2) The SAS-6 ring model as a tool to redirect centriole organization. Utilizing predictions from the SAS-6 ring model, we will assay the consequences for centrioles and cilia of altering the diameter and symmetry of the structure. 3) Determining the architecture of C. elegans centrioles. We will conduct molecular counting and cryo-ET of purified C. elegans centrioles to determine if they contain a spiral or a cartwheel, as well as identify SAS-6-interacting components. 4) Comprehensive 3D map and proteomics of Trichonympha centriole. We will obtain a ~35 Å 3D map of the complete T. agilis centriole, perform proteomic analysis to identify its constituents and test their function using RNAi. 5) Regulation of cartwheel height and centriole length. We will explore whether cartwheel height is set by SAS-6 proteins and perform screens in human cells to identify novel components regulating cartwheel height and centriole length. 6) Novel cell free assay for cartwheel assembly and centriole formation. Using SAS-6 proteins on a lipid monolayer as starting point, we will develop and utilize a cell-free assay to reconstitute cartwheel assembly and centriole format

Keywords: centriole,carthweel,sas-6 proteins,human cells,c. elegans,trichonympha
Topological, Algebraic, Differential Methods in Classification and Moduli Theory (TADMICAMT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Mathematical foundations
Countries involved: Germany
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-04-01
End date: 2020-03-31
Duration (months): 72.0
Total project cost (EUR): 1725420.0
EU funding (EUR): 1725420.0
Participants: 1
Project status: CLOSED

Moduli of curves with symmetries:determine the stable irreducible components of the moduli space of curves of genus g with an action of a finite group G, using a new homological invariant. Stable means: for g sufficiently large, or for sufficiently large numerical branching function. Higher homological stabilization for these moduli spaces. Faithful actions of the absolute Galois group on moduli spaces of marked varieties, triangle curves, varieties isogenous to a product, Beauville surfaces. Change of fundamental group. Fields of definitions of triangle curves and the scheme representing triangle curves. Uniformization: characterization of proj. var. whose universal cover is a given bounded symmetric domain (Catanese-Di Scala did the case of tube domains). Orbifold Uniformization: where we have a quotient of a non free action, or a noncompact such quotient. Classification of surfaces with genus 0 having the bidisk as universal cover. Symmetric differentials and fundamental groups of some ball quotients. Topological methods in Moduli Theory: strong, weak and pseudo rigidity for the Inoue type varieties of Bauer and Catanese (free quotients of ample divisors on projective varieties which are K(\pi, 1)). With Lonne and Wajnryb, using methods by Auroux and Katzarkov: study canonical symplectic structures and deformation types of some simply connected algebraic surfaces, determining braid group factorizations associated to subcanonical projections. More general bicoloured braid factorizations associated to general projections. Teichmueller space of certain algebraic surfaces. Classification and Moduli of surfaces with low invariants. Surfaces of geometric genus 0: new construction techniques, structure of fundamental groups, moduli spaces, existence questions for surfaces with certain invariants, for homotopy quadrics, structure of fake quadrics.

Keywords: moduli spaces,automorphisms of curves,algebraic surfaces,uniformization,quotients of bounded domains,absolute galois group,mapping class groups,monodromy,fibrations,deformation types,rigidity
Roles of Palmitoylation networks in ER architecture and functions (PALMERA)

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: Switzerland
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 2443949.0
EU funding (EUR): 2443949.0
Participants: 1
Project status: CLOSED

The endoplasmic reticulum (ER) is the largest intracellular organelle of mammalian cells. It fulfills major functions such as folding and quality control of membrane proteins, lipid biosynthesis, calcium storage, and modulation of apoptosis. This diversity of functions is accompanied by a complex 3D architecture, the maintenance of which is essential, since alterations lead to disease. How this architecture is generated, how proteins localize to specific subdomains and how structure and functions are coordinated is poorly understood. Our unpublished observations show that many ER membrane proteins, involved in key functions or in organelle shaping, are lipid modified, by the same palmitoyltransferases, and in a switch-like manner. We hypothesize that palmitoyltransferases act as regulators of the mammalian ER, controlling the function of a network of key proteins through reversible acylation, analogous to the control of signaling networks by phosphorylation. To establish the role of palmitoylation in coordinating ER structure/function, we propose a program integrating biochemical, functional and modeling approaches. We will determine the ER palmitome and investigate the impact of acylation on the function of individual proteins, on ER architecture and on the ER lipidome. We will analyze the interplay between and ubiquitination in controlling ER functions. Since we found that the DHHC6 palmitoytransferase is essential in mice and palmitoylates key ER proteins, we will study this enzyme in depth in terms of structure, function, target specific and regulation. Finally, we will combine the information emanating from these studies into a mathematical model of the ER palmitoylation network.

Keywords: endoplasmic reticulum,palmitoylation
The Role of Neuropeptides in Learning and Memory. (PEPTIDELEARNING)

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: Belgium
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2020-01-31
Duration (months): 72.0
Total project cost (EUR): 2463028.0
EU funding (EUR): 2463028.0
Participants: 1
Project status: CLOSED

Humanity has always been intrigued by the nearly mythical properties of the brain. With its billions of neurons and innumerable connections, the brain is of such complex nature, that trying to understand it may seem a vain project. Yet, by using the ‘mini-brain’ of the model organism Caenorhabditis elegans, which shares many components with the human brain but counts only 302 neurons, thorough research can penetrate into this complexity. We here pursue to deliver a much-needed understanding of how learning and memory processes are regulated by neuropeptide signaling in the brain. Neuropeptides are small regulatory proteins that are implicated in a variety of processes. Growing evidence exists for their involvement in learning and memory, but how they exert these effects is largely unexplored. In C. elegans we recently disentangled a conserved vasopressin/ocytocin-related system that –as in humans– mediates associative learning. As such, we can deliver the experience, model and logical approach to provide detailed insights in neuropeptidergic control of learning and memory. We will first identify the endogenous ligand of all orphan C. elegans neuropeptide GPCRs, as this will provide the essential basis to build this project on. Mutants of neuropeptide-receptor pairs will then be tested for their ability to learn or maintain associative short- or long-term memory. We will also define in which cells and circuits relevant neuropeptides and receptors are needed for these functions, in order to generate models of neuropeptidergic control of learning and memory. We envisage the use of novel tools and cutting-edge experimental setups to take this research beyond its current horizon. Via single cell RNA sequencing, optogenetic analyses and in vivo calcium imaging, we will develop a workflow to build integrative models of associative learning and memory processes mediated by neuropeptides, which will serve as a scaffold for the study of these processes in more complex brains.

Keywords: neuropeptide - model organism - caenorhabditis elegans
Complex analysis and statistical physics (COMPASP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Mathematical foundations
Countries involved: Switzerland
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-01-01
End date: 2019-12-31
Duration (months): 72.0
Total project cost (EUR): 1995900.0
EU funding (EUR): 1995900.0
Participants: 1
Project status: CLOSED

The goal of this project is to achieve breakthroughs in a few fundamental questions in 2D statistical physics, using techniques from complex analysis, probability, dynamical systems, geometric measure theory and theoretical physics. Over the last decade, we significantly expanded our understanding of 2D lattice models of statistical physics, their conformally invariant scaling limits and related random geometries. However, there seem to be serious obstacles, preventing further development and requiring novel ideas. We plan to attack those, in particular we intend to: (A) Describe new scaling limits by Schramm’s SLE curves and their generalizations, (B) Study discrete complex structures and use them to describe more 2D models, (C) Describe the scaling limits of random planar graphs by the Liouville Quantum Gravity, (D) Understand universality and lay framework for the Renormalization Group Formalism, (E) Go beyond the current setup of spin models and SLEs. These problems are known to be very difficult, but fundamental questions, which have the potential to lead to significant breakthroughs in our understanding of phase transitions, allowing for further progresses. In resolving them, we plan to exploit interactions of different subjects, and recent advances are encouraging.

Keywords: schramm-loewner evolution,sle,percolation,self avoiding walk,ising model,planar map,conformal map
Studying in vivo differentiation of monocytes into intestinal macrophages and their impact on gut homeostasis (MONOTOMACRO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Israel
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-01-01
End date: 2018-12-31
Duration (months): 60.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

Monocytes are central players in inflammation. Progress in understanding their differentiation in target tissues bears potential to manipulate their activities for therapeutic purposes. Here we propose to study the generation of intestinal macrophages (MΦs) as a paradigm, taking advantage of a unique experimental system to elucidate in vivo monocyte fates. The intestine hosts billions of bacteria that assist food uptake, but also pose a challenge, as we have to tolerate these beneficial commensals, yet rapidly mount immune responses to invading pathogens. Failure to maintain this balance causes inflammatory bowel disorders (IBD). Gut resident MΦs are key players in gut homeostasis and inflammation. Here we will study molecular parameters governing their generation from monocytes, as well as their interactions with the immediate tissue surrounding under pathological conditions. We focus on the molecular mechanisms leading to education of monocytes in small and large intestine using genome wide profiling of gene expression, chromatin state and transcription factor binding of monocytes and MΦs. Secondly, we will investigate epithelial and microflora-derived instructing cues, as well as sensory molecules on the MΦs that drive the education. Thirdly, we will study the impact of MΦs that fail to be trained and their role in the development of inflammation. Finally, we will use the insights gained to develop monocyte manipulation strategies that could aid the future development of IBD therapies. Our experimental system allows to follow the in vivo differentiation of engrafted monocytes, as physiological precursor cells, that acquire in a rapid synchronized development in the gut tissue physiologically relevant fates. Expected include (1) fundamental insight into the acquisition and maintenance of MΦ identities in a complex tissue context, (2) progress in our understanding of gut homeostasis and IBD, and (3) guiding insights for future monocyte-targeted therapy.

Keywords: macrophage differentiation,adoption of cell fates in tissue context,intestinal inflammation,host microbe interactions,inflammatory bowel disorder (ibd),colitis,monocyte manipulation
ACCRETING BLACK HOLES AND COSMIC FEEDBACK (FEEDBACK)

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: 2014-02-01
End date: 2019-09-30
Duration (months): 68.0
Total project cost (EUR): 2498064.0
EU funding (EUR): 2498064.0
Participants: 1
Project status: CLOSED

The black hole at the centre of every massive galaxy bulge appears to play a controlling role in the final stellar mass of that bulge. This is especially true for the most massive galaxies at the centres of cool core clusters where X-ray observations clearly show energy being fed back into the surrounding gas which would otherwise cool and form more stars at high rates. Although the total energy budget for this phenomenon is clear, the details by which the processes operate are not. This proposal aims to further our understanding of how accreting black holes generate and feed back energy into the surrounding gas, how it is dissipated and establishes a heating / cooling balance and how the black hole, galaxy and feedback co-evolve. The work will focus on the broad iron line and X-ray reflection spectral and reverberation components which we have discovered in the spectra of accreting black holes, on X-ray imaging spectroscopy of cool core clusters of galaxies and on the filamentary nebulosity commonly observed around the central galaxy in such clusters. The work will involve X-ray observations together with data from other wavebands where relevant. We shall also consider theoretical aspects of the problem and interpret the whole phenomenon. The current X-ray telescopes (Chandra, XMM and Suzaku) are now mature and we understand how to use them optimally, particularly with longer exposures. Major new data are coming from NuSTAR (launched 2012), which is now opening up the hard X-ray band, and from ASTRO-H (to be launched 2014) which will open up the iron-K band to high spectral resolution and thus direct measurement of the velocity field of the hot and cold components of AGN Feedback.