Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Quantum Logic Enabled test of Discrete Symmetries (QLEDS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Fundamental constituents of matter
Countries involved: Germany
Call:  (ERC-2013-StG, 2013)
Start date: 2013-09-01
End date: 2020-02-29
Duration (months): 78.0
Total project cost (EUR): 1619640.0
EU funding (EUR): 1619640.0
Participants: 1
Project status: CLOSED

This proposal aims to apply ion-trap quantum logic techniques to precision measurements on individual (anti-)protons for fundamental physics tests. In particular, we aim to measure g-factors of single (anti-)protons as a precise test of CPT symmetry. This requires a method to detect single (anti-)proton spin flips. Current efforts based on classical “magnetic bottle” techniques are hurt by the extreme difficulty and slowness of the spin state detection. Discrete and direct state measurement is a prerequisite for inaccuracies below 10-6 and has not been achieved yet. Towards this end, we will employ a radically different approach and use quantum logic techniques developed by the PI in the NIST ion storage group of D. J. Wineland [Nature 476, 181(2011); Nature 471, 196(2011)]. This will allow us to transfer the (anti-)proton’s spin state to a nearby trapped atomic “logic” ion and subsequently read it out using standard quantum logic detection techniques along the lines of Heinzen and Wineland [PRA 42, 2977; J. Res. NIST 103, 259 (1998)]. The same ideas are also at the root of NIST’s world-record single-ion Al+ frequency standard. Ultimately, this quantum logic technique will lead to a precise test of CPT symmetry, a fundamental symmetry within the standard model of particle physics, by comparing the proton’s and the antiproton’s g-factor with fast detection and single spin-flip resolution. It thus has the potential to reach inaccuracies below 10-9, exceeding the state-of-the-art for the antiproton g-factor by six orders of magnitude. Such a measurement is urgently needed to complement ongoing tests with electrons and positrons. It is closely intertwined with our desire to understand the observed matter-antimatter imbalance in the universe and to obtain a unified description of matter and interactions. Further, the project will considerably broaden the arsenal of quantum state manipulation techniques in Penning traps and possibly impact high precision mass measurement.
On the move: Motor-cargo and motor-microtubule interactions studied with quantitative, high spatio-temporal resolution microscopy in vivo (MOTORS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Condensed matter physics
Countries involved: Spain
Call:  (ERC-2013-StG, 2013)
Start date: 2013-09-01
End date: 2017-12-31
Duration (months): 52.0
Total project cost (EUR): 1288535.0
EU funding (EUR): 1288535.0
Participants: 1
Project status: TERMINATED

Intracellular transport plays a key role in many cellular processes. Cells rely on a well-regulated, two-way transport system that consists of molecular motors and cytoskeletal filaments for their correct functioning. In nerve cells, breakdown of transport is tightly linked to neurodegenerative diseases. Understanding what goes wrong with intracellular transport during disease requires knowledge of how motors work inside cells to transport cargo. While much effort has been devoted to understanding motor mediated intracellular transport, our knowledge of motor-cargo and motor-microtubule interactions in the cellular environment is still very rudimentary. The small size of motors, the complex architecture of their microtubule tracks, and the inherently dynamic nature of transport have made these interactions virtually inaccessible to observation in living cells until recently. With new advances in fluorescence microscopy, in particular with the development of ground-breaking methods that surpass the diffraction limit, we can finally begin to address this challenging problem. In this ambitious proposal we will study, at an unprecedented level of detail, the nanoscale organization and stoichiometry of motor proteins on their cargo and interactions of motor proteins with microtubules in living cells. We will achieve this goal by using a multidisciplinary approach that combines cutting-edge biophysical tools such as single particle tracking, quantitative single molecule counting and super-resolution nanoscopy with novel genetic manipulation and fluorescence labeling methods. Using these unique set of tools we will unravel the molecular mechanisms that regulate motors to achieve efficient transport. The results obtained in this proposal will provide, for the first time, a detailed picture of how motors function inside living cells, greatly enhancing our knowledge of a fundamental cell biological process and of its implications in disease.

Keywords: super resolution nanoscopy,storm,single molecule biophysics,motor proteins,intracellular transport
Protease Activated X-Ray Contrast Agents for Molecular Imaging of Vulnerable Atherosclerotic Plaques and Cancer Development using Spectral CT (CT-PROBES)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Israel
Call:  (ERC-2013-StG, 2013)
Start date: 2013-12-01
End date: 2018-11-30
Duration (months): 60.0
Total project cost (EUR): 1499780.0
EU funding (EUR): 1499780.0
Participants: 1
Project status: CLOSED

The major causes of death in the Western world are cardiovascular diseases and cancer. More accurate detection of these diseases will improve clinical outcomes. Thus, we will develop unique X-ray contrast reagents for use in spectral computerized tomography (CT) that bind active proteases to reveal the exact location and stage of cancer and atherosclerosis. Activity-based probes (ABPs) are small molecules that covalently bind to active proteases. Based on our success in developing optical ABPs for non-invasive optical detection of cancer and atherosclerosis, we will focus on two novel types of reagents: (1) ABPs conjugated to the various contrast elements that can be visualized by x-rays. (2) “smart probes” conjugated to different contrast reagents on each side of the molecule to overcome clearance limitations. Protease found in diseased tissue will selectively bind and remove a part of the molecule, changing the physical properties of the bound probe. Thus, different signals from bound and unbound probes could be detected by photon counting spectral CT scanners. Our initial target, cysteine cathepsin proteases, are overexpressed and activated in cancer and arthrosclerosis. The level of active cathepsins correlates with progression of both diseases, thereby serving as a promising biomarker for these pathologies. The “smart probes” are an innovative type of spectral CT agent that will enable high-resolution rapid imaging in humans before probe clearance. Our probes increase imaging sensitivity since the contrast element remains at the desired site. Moreover, the levels of active cathepsins will reveal critical information regarding disease progression, yielding more accurate diagnoses and improved personalized treatment. For example, these reagents can distinguish between a vulnerable and stable atherosclerotic plaque. Thus, our novel probes will directly reduce cancer and cardiovascular disease mortality by enabling earlier and more accurate disease detection.

Keywords: activity-based probes,protease,cathepsin,atherosclerosis,cancer,ct contrast agents
Firm Networks Trade and Growth (FINET)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Individuals, institutions and markets
Countries involved: France
Call:  (ERC-2013-StG, 2013)
Start date: 2013-12-01
End date: 2019-11-30
Duration (months): 72.0
Total project cost (EUR): 1169400.0
EU funding (EUR): 1169400.0
Participants: 2
Project status: CLOSED

The general theme of this research is to introduce the notion of large-scale economic networks into the mainstream of economics, in particular in macroeconomics and international trade. Economic agents often do not have access to all the relevant information they may need: whom they know, whom they interact with represents a small fraction of all possible interactions. I model this limited set of interactions as a network: agents are nodes, and they only interact with other agents they have formed a link with. What is the shape of this network of linkages between agents, and how does it evolve? More importantly, what are the aggregate implications of the shape of this network? These are the broad questions I will address in this research. I will consider six specific applications of this unifying idea in various fields: international trade, IO, macroeconomics and growth. In international trade, we have only a very crude understanding of the frictions that prevent most firms from exporting. I propose to model trade frictions as a dynamic network: at a point in time, a given exporter only has information about a limited set of potential customers in a few foreign countries; over time, this exporter discovers new export opportunities, and its network of customers evolves dynamically. I offer theoretical and empirical tools to understand and analyze the properties of this network, and show how it shapes aggregate trade patterns. In IO and macroeconomics, most plants only have few suppliers. I will model the input-output linkages between plants as a dynamic network; I offer theoretical and empirical tools to analyze this network, and show how it shapes the propagation of plant level shocks to generate aggregate fluctuations. Human capital accumulation is key to economic growth and development, with workers learning from each other. I will model these growth-enhancing interactions as a dynamic network; I will show how the properties of this network shape long run growth.
Structural and mechanistic studies of RNA-guided and RNA-targeting antiviral defense pathways (ANTIVIRNA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Switzerland
Call:  (ERC-2013-StG, 2013)
Start date: 2013-11-01
End date: 2018-10-31
Duration (months): 60.0
Total project cost (EUR): 1467180.0
EU funding (EUR): 1467180.0
Participants: 1
Project status: CLOSED

The evolutionary pressures exerted by viruses on their host cells constitute a major force that drives the evolution of cellular antiviral mechanisms. The proposed research is motivated by our interest in the roles of protein-RNA interactions in both prokaryotic and eukaryotic antiviral pathways and will proceed in two directions. The first project stems from our current work on the CRISPR pathway, a recently discovered RNA-guided adaptive defense mechanism in bacteria and archaea that silences mobile genetic elements such as viruses (bacteriophages) and plasmids. CRISPR systems rely on short RNAs (crRNAs) that associate with CRISPR-associated (Cas) proteins and function as sequence-specific guides in the detection and destruction of invading nucleic acids. To obtain molecular insights into the mechanisms of crRNA-guided interference, we will pursue structural and functional studies of DNA-targeting ribonuceoprotein complexes from type II and III CRISPR systems. Our work will shed light on the function of these systems in microbial pathogenesis and provide a framework for the informed engineering of RNA-guided gene targeting technologies. The second proposed research direction centres on RNA-targeting antiviral strategies employed by the human innate immune system. Here, our work will focus on structural studies of major interferon-induced effector proteins, initially examining the allosteric activation mechanism of RNase L and subsequently focusing on other antiviral nucleases and RNA helicases, as well as mechanisms by which RNA viruses evade the innate immune response of the host. In our investigations, we plan to approach these questions using an integrated strategy combining structural biology, biochemistry and biophysics with cell-based functional studies. Together, our studies will provide fundamental molecular insights into RNA-centred antiviral mechanisms and their impact on human health and disease.

Keywords: crispr,endonuclease,protein-rna interactions,innate immunity,interferon
3D structures of bacterial supramolecular assemblies by solid-state NMR (ASSEMBLYNMR)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Germany,Germany
Call:  (ERC-2013-StG, 2013)
Start date: 2014-05-01
End date: 2019-04-30
Duration (months): 60.0
Total project cost (EUR): 1456000.0
EU funding (EUR): 1456000.0
Participants: 2
Project status: CLOSED

Supramolecular assemblies – formed by the self-assembly of hundreds of protein subunits – are part of bacterial nanomachines involved in key cellular processes. Important examples in pathogenic bacteria are pili and type 3 secretion systems (T3SS) that mediate adhesion to host cells and injection of virulence proteins. Structure determination at atomic resolution of such assemblies by standard techniques such as X-ray crystallography or solution NMR is severely limited: Intact T3SSs or pili cannot be crystallized and are also inherently insoluble. Cryo-electron microscopy techniques have recently made it possible to obtain low- and medium-resolution models, but atomic details have not been accessible at the resolution obtained in these studies, leading sometimes to inaccurate models. I propose to use solid-state NMR (ssNMR) to fill this knowledge-gap. I could recently show that ssNMR on in vitro preparations of Salmonella T3SS needles constitutes a powerful approach to study the structure of this virulence factor. Our integrated approach also included results from electron microscopy and modeling as well as in vivo assays (Loquet et al., Nature 2012). This is the foundation of this application. I propose to extend ssNMR methodology to tackle the structures of even larger or more complex homo-oligomeric assemblies with up to 200 residues per monomeric subunit. We will apply such techniques to address the currently unknown 3D structures of type I pili and cytoskeletal bactofilin filaments. Furthermore, I want to develop strategies to directly study assemblies in a native-like setting. As a first application, I will study the 3D structure of T3SS needles when they are complemented with intact T3SSs purified from Salmonella or Shigella. The ultimate goal of this proposal is to establish ssNMR as a generally applicable method that allows solving the currently unknown structures of bacterial supramolecular assemblies at atomic resolution.
Mapping the Deprived Visual System: Cracking function for prediction (MADVIS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: The Human Mind and its complexity
Countries involved: Italy
Call:  (ERC-2013-StG, 2013)
Start date: 2014-04-01
End date: 2020-03-31
Duration (months): 72.0
Total project cost (EUR): 1488987.0
EU funding (EUR): 1488987.0
Participants: 2
Project status: CLOSED

One of the most striking demonstrations of experience-dependent plasticity comes from studies of blind individuals showing that the occipital cortex (traditionally considered as purely visual) massively changes its functional tuning to support the processing of non-visual inputs. These mechanisms of crossmodal plasticity, classically considered compensatory, inevitably raise crucial challenges for sight-restoration. The neglected relation between crossmodal plasticity and sight-recovery will represent the testing ground of MADVIS in order to gain important novel insights on how specific brain regions become, stay and change their functional tuning toward the processing of specific stimuli. The main goal of MADVIS is therefore to make a breakthrough on two fronts: (1) understanding how visual deprivation at different sensitive periods in development affects the functional organization and connectivity of the occipital cortex; and (2) use the fundamental knowledge derived from (1) to test and predict the outcome of sight restoration. Using a pioneering interdisciplinary approach that crosses the boundaries between cognitive neurosciences and ophthalmology, MADVIS will have a large impact on our understanding of how experience at different sensitive periods shapes the response properties of specific brain regions. Finally, in its attempt to fill the existing gap between crossmodal reorganization and sight restoration, MADVIS will eventually pave the way for a new generation of predictive surveys prior to sensory restoration.

Keywords: crossmodal plasticity,blindness,sight-restoration,occipial,sensory,cognitive,domain specialization,vision,audition,touch.
Series-Parallel Elastic Actuators for Robotics (SPEAR)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Systems and communication engineering
Countries involved: Belgium
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 1498620.0
EU funding (EUR): 1498620.0
Participants: 1
Project status: CLOSED

Actuators are key components for moving and controlling a mechanism or system. However, the torque and efficiency of the current state-of-the-art actuators are insufficient and much lower than in humans. There are several applications (including prostheses, exoskeletons and running robots) where the unavailability of suitable actuators hinders the development of well-performing machines with capabilities comparable to a human. Remarkable, the power density and efficiency of electric motors are higher than a human muscle, so the problems of insufficient torque and efficiency resides in the transmission of the power and that the motors are not used at their highest efficiency. The first innovation of SPEAR is to solve the torque and efficiency problems, by investigating in depth a novel actuation paradigm, which I call Series-Parallel Elastic Actuation (SPEA) and that goes beyond variable impedance actuators. This new actuation paradigm is inspired by the series-parallel organisation of the muscle fibres. Modularity in actuation is currently introduced by placing in all joints the same motor, leading to over- or underactuated joints. In our body however, all the skeletal muscles are built of the same basic actuation unit: a muscle fibre. Modularity in actuation in a biological system is not at muscle level, but on a sublevel: the muscle fibre. SPEAR will introduce a second major innovation: the SPEA will introduce a basic actuation unit, a “transistor for actuation”. Such a SPEA-element is a missing link in robotics and will innovate the way robots are designed and built. The project will study the theoretical framework, the design principles, the control algorithms and the validation of demonstrators. SPEAR will fully answer all the research challenges and explore the frontiers of this novel actuation paradigm, leading to a tremendous impact on all engineered, actuated systems, especially in robotics.

Keywords: variable impedance actuator,compliant actuator,variable stiffness actuator,soft actuator,series elastic actuator,parallel spring,energy efficiency,human-robot interaction,robotics
Novel insights into cardiac regeneration through studies in the zebrafish (ZEBRAHEART)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Switzerland,Spain
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-07-31
Duration (months): 66.0
Total project cost (EUR): 1499215.0
EU funding (EUR): 1499215.0
Participants: 2
Project status: CLOSED

Myocardial infarction (MI) leads to cardiomyocyte death and accumulation of myofibroblasts (MFs) at the site of injury, which produce large amounts of extracellular matrix (ECM), generating a scar. Initially, cardiac fibrosis protects from ventricular wall rupture, but subsequent myocardial remodelling causes heart failure, representing a leading cause of death in Europe. While MFs play a central role in cardiac fibrosis, there is confusion on their origin, a lack of specific markers and the existence of a unique MF type is debatable. Different MF might reveal distinct characteristics regarding ECM production, contractility, and autophagy, making them more or less pernicious. While in humans cardiac fibrosis is irreversible, other vertebrates have a remarkable capacity to regenerate damaged tissue. We recently established a zebrafish MI model and found that cardiac fibrosis is reversible and occurs as an intermediate step during regeneration. Here, the endogenous mechanisms of MFs and ECM regression will be explored. In addition, MF origin, types and fate will be characterized and manipulated to improve regeneration. As in mammals, cardiac injury elicits an inflammatory response in the zebrafish. The regenerative capacity of a species has been directly linked to features of its immune system, but surprisingly little is known on zebrafish leukocyte subtypes. We will study the role of macrophages and particularly analyse a subtype, which accumulates in the outer mesothelial layer of the heart, the epicardium. Epicardial derived cells play a key role as a trophic factor and progenitor cell source, and a first step towards regeneration includes the reestablishment of the epicardial layer. The zebrafish will offer a screening platform for small molecules triggering its activation. In sum, the project will increase the knowledge on the molecular and cellular basis of fibrosis regression, provide novel MF markers and identify new drugs to enhance cardiac regeneration.

Keywords: regeneration,zebrafish,myofibroblast,fibrosis,macrophage,wt1,glia,pericyte,thrombocyte