Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
FIC-Mediated Post-Translational Modifications at the Pathogen-Host Interface: Elucidating Structure, Function and Role in Infection (FICMODFUN)

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: Switzerland
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 1699857.6
EU funding (EUR): 1699857.6
Participants: 1
Project status: CLOSED

The ubiquitous FIC domain catalyzes post-translational modifications (PTMs) of target proteins; i.e. adenylylation (=AMPylation) and, more rarely, uridylylation and phosphocholination. Fic proteins are thought to play critical roles in intrinsic signaling processes of prokaryotes and eukaryotes; however, a subset encoded by bacterial pathogens is translocated via dedicated secretion systems into the cytoplasm of mammalian host cells. Some of these host-targeted Fic proteins modify small GTPases leading to collapse of the actin cytoskeleton and other drastic cellular changes. Recently, we described a large set of functionally diverse homologues in pathogens of the genus Bartonella that are required for their “stealth attack” strategy and persistent course of infection [1, 2]. Our preliminary functional analysis of some of these host-targeted Fic proteins of Bartonella demonstrated adenylylation activity towards novel host targets (e.g. tubulin and vimentin). Moreover, in addition to the canonical adenylylation activity they may also display a competing kinase activity resulting from altered ATP binding to the FIC active site. Finally, we described a conserved mechanism of FIC active site auto- inhibition that is relieved by a single amino acid exchange [1], thus facilitating functional analysis of any Fic protein of interest. Despite this recent progress only a few Fic proteins have been functionally characterized to date; our understanding of the functional plasticity of the FIC domain in mediating diverse target PTMs and their specific roles in infection thus remains limited. In this project, we aim to study the vast repertoire of host-targeted Fic proteins of Bartonella to: 1) identify novel target proteins and types of PTMs; 2) study their physiological consequences and molecular mechanisms of action; and 3) analyze structure-function relationships critical for FIC-mediated PTMs and infer from these data determinants of target specificity, type of PTM and mode of regulation. At the forefront of infection biology research, this project is ground-breaking as (i) we will identify a plethora of novel host target PTMs that are critical for a “stealth attack” infection strategy and thus will open new avenues for investigating fundamental mechanisms of persistent infection; and (ii), we will unveil the molecular basis of the remarkable functional versatility of the structurally conserved FIC domain.

Keywords: post-translational modification,bacterial toxin-antitoxin systems,bacterial effector,kinase,enzyme engineering,synthetic biology
The language of astrocytes: multilevel analysis to understand astrocyte communication and its role in memory-related brain operations and in cognitive behavior (ASTROMNESIS)

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: Switzerland
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 2513895.76
EU funding (EUR): 2513895.76
Participants: 1
Project status: CLOSED

In the 90s, two landmark observations brought to a paradigm shift about the role of astrocytes in brain function: 1) astrocytes respond to signals coming from other cells with transient Ca2+ elevations; 2) Ca2+ transients in astrocytes trigger release of neuroactive and vasoactive agents. Since then, many modulatory astrocytic actions and mechanisms were described, forming a complex - partly contradictory - picture, in which the exact roles and modes of astrocyte action remain ill defined. Our project wants to bring light into the “language of astrocytes”, i.e. into how they communicate with neurons and, ultimately, address their role in brain computations and cognitive behavior. To this end we will perform 4 complementary levels of analysis using highly innovative methodologies in order to obtain unprecedented results. We will study: 1) the subcellular organization of astrocytes underlying local microdomain communications by use of correlative light-electron microscopy; 2) the way individual astrocytes integrate inputs and control synaptic ensembles using 3D two-photon imaging, genetically-encoded Ca2+ indicators, optogenetics and electrophysiology; 3) the contribution of astrocyte ensembles to behavior-relevant circuit operations using miniaturized microscopes capturing neuronal/astrocytic population dynamics in freely-moving mice during memory tests; 4) the contribution of astrocytic signalling mechanisms to cognitive behavior using a set of new mouse lines with conditional, astrocyte-specific genetic modification of signalling pathways. We expect that this combination of groundbreaking ideas, innovative technologies and multilevel analysis makes our project highly attractive to the neuroscience community at large, bridging aspects of molecular, cellular, systems and behavioral neuroscience, with the goal of leading from a provocative hypothesis to the conclusive demonstration of whether and how “the language of astrocytes” participates in memory and cognition.

Keywords: astrocyte communication astrocytes and synaptic transmission in vivo ca2+ imaging and astrocytes
Superamphiphobic surfaces for chemical processing (SUPRO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Products and process engineering
Countries involved: Germany
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-03-01
End date: 2020-02-29
Duration (months): 72.0
Total project cost (EUR): 2497800.0
EU funding (EUR): 2497800.0
Participants: 1
Project status: CLOSED

Superhydrophobic surfaces hold enormous promise as future self-cleaning or anti-fouling coatings. Their widespread use was, however, limited by contamination with oils and dissolved substances and insufficient mechanical stability. Superamphiphobic surfaces prevent contamination. They not only repel water but also non-polar liquids, surfactant and protein solutions. We recently developed a concept to fabricate transparent, robust superamphiphobic coatings, that is potentially upscalable for industrial mass production. The almost contact-free interface will open up new opportunities in membrane technology, solvent-free production of microspheres, in microfluidics, and in preventing biofilm formation. With targeted experiments and simulation we relate the microscopic structure of superamphiphobic layers to their impalement pressure, roll-off angle, mechanical strength and hydrodynamic drag. Based on these insight, improved and adapted designs will be developed. This project will make it possible to determine the potential of superamphiphobic layers in novel approaches to microchemical processing including improved transport, synthesis and characterization.

Keywords: superhydrophobicity,surfaces and interfaces
Non-ordered nanoparticle superstructures – aerogels as efficient (electro-)catalysts (AEROCAT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Materials and Synthesis
Countries involved: Germany
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-07-31
Duration (months): 66.0
Total project cost (EUR): 2194000.0
EU funding (EUR): 2194000.0
Participants: 1
Project status: CLOSED

AEROCAT aims at the elucidation of the potential of nanoparticle derived aerogels in catalytic applications. The materials will be produced from a variety of nanoparticles available in colloidal solutions, amongst which are metals and metal oxides. The evolving aerogels are extremely light, highly porous solids and have been demonstrated to exhibit in many cases the important properties of the nanosized objects they consist of instead of simply those of the respective bulk solids. The resulting aerogel materials will be characterized with respect to their morphology and composition and their resulting (electro-)catalytic properties examined in the light of the inherent electronic nature of the nanosized constituents. Using the knowledge gained within the project the aerogel materials will be further re-processed in order to exploit their full potential relevant to catalysis and electrocatalysis. From the vast variety of possible applications of nanoparticle-based hydro- and aerogels like thermoelectrics, LEDs, pollutant clearance, sensorics and others we choose our strictly focused approach (i) due to the paramount importance of catalysis for the Chemical Industry, (ii) because we have successfully studied the Ethanol electrooxidation on a Pd-nanoparticle aerogel, (iii) we have patented on the oxygen reduction reaction in fuel cells with bimetallic aerogels, (iv) and we gained first and extremely promising results on the semi-hydrogenation of Acetylene on a mixed Pd/ZnO-nanoparticle aerogel. With this we are on the forefront of a research field which impact might not be overestimated. We should quickly explore its potentials and transfer on a short track the knowledge gained into pre-industrial testing.

Keywords: nanoparticle based aerogels,nanocrystals,heterogeneous catalysis,electrocatalysis
Co-evolution of viruses, plasmids and cells in Archaea: pattern and process (EVOMOBIL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: France,France
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-02-01
End date: 2019-08-31
Duration (months): 67.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 2
Project status: CLOSED

Interactions between cells and mobile elements such as viruses and plasmids (the mobilome) have played a major role in life evolution. However, up to now, evolutionary studies have mainly focused on cellular genomes (building species trees). My project is to reconstruct the history of interaction between cells, plasmids and viruses (PVs) at the domain level to answer questions such as: to which extent PVs co-evolved with their hosts? How was cellular history influenced by PVs? What is the main directionality of gene fluxes between PVs and cells? The project will focus on Archaea, the third domains of life, because we only have a robust species phylogeny for this domain. We will perform an exhaustive description of PV families in all available archaeal genomes, as well as free PVs, using a combination of in silico methods and expert analyses. Phylogenetic and network analyses will be used to reconstruct the history of PVs with the objective to quantify horizontal versus vertical evolution and to sort out the web and tree-like components of archaeal history. Preliminary analyses have revealed the importance of horizontal gene transfer (HGT) in archaeal evolution. However, the processes behind these HGT remain mysterious, especially for hyperthermophiles. In parallel to our in silico analyses, we will explore the possible role of membrane vesicles (MV) in HGT. We have shown that archaeal MVs can transfer DNA and that some of them harbour plasmid or viral genomes. We want tackle questions such as: can these MVs transfer DNA between different species, different orders or even different domains? We will also study MV formation and fusion in comparison to those involved in viral infection to better understand possible evolutionary and physiological connections between MV and PV. Production of MV is a universal process and their role in life evolution could have been largely underestimated up to now.

Keywords: extracellular membrane vesicles,archaea,plasmids
Adding Another Dimension – Arrays of 3D Bio-Responsive Materials (ADREEM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: United Kingdom
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-11-01
End date: 2019-10-31
Duration (months): 60.0
Total project cost (EUR): 2310884.0
EU funding (EUR): 2310884.0
Participants: 1
Project status: CLOSED

This proposal is focused in the areas of chemical medicine and chemical biology with the key drivers being the discovery and development of new materials that have practical functionality and application. The project will enable the fabrication of thousands of three-dimensional “smart-polymers” that will allow: (i). The precise and controlled release of drugs upon the addition of either a small molecule trigger or in response to disease, (ii). The discovery of materials that control and manipulate cells with the identification of scaffolds that provide the necessary biochemical cues for directing cell fate and drive tissue regeneration and (iii). The development of new classes of “smart-polymers” able, in real-time, to sense and report bacterial contamination. The newly discovered materials will find multiple biomedical applications in regenerative medicine and biotechnology ranging from 3D cell culture, bone repair and niche stabilisation to bacterial sensing/removal, while offering a new paradigm in drug delivery with biomarker triggered drug release.
The Plant Immune System: Epistasis and Fitness-Tradeoffs (IMMUNEMESIS)

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: Germany
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-03-01
End date: 2019-11-30
Duration (months): 69.0
Total project cost (EUR): 2499900.0
EU funding (EUR): 2499900.0
Participants: 1
Project status: CLOSED

A fundamental question in biology is how multicellular organisms distinguish self and non-self. The requirement to specifically recognize only foreign cells and molecules constrains the diversification of the immune system, resulting in conflicts between effective detection of enemies, adaptive changes in the cellular machinery and mating with divergent genotypes from the same species. In plants, there is generally a trade-off between immunity and growth, and immune system activation is often associated with impaired development. There are many examples of autoimmunity in hybrids, caused by a gene product from one parent erroneously interpreting a gene product from the other parent as foreign. This is not surprising, given the extraordinary diversity of many immune genes. On the other hand, hybrid vigor, or heterosis, is commonly observed in F1 progeny from two inbred parents, and this is widely exploited in breeding. Thus, it is also of practical importance to understand how outcrossing affects the plant immune system. We hypothesize that overt hybrid autoimmunity represents only the tip of the iceberg, and that there are many more subtle non-additive genetic interactions that affect both the plant immune system and growth. We therefore propose a comprehensive research program to dissect epistatic interactions with effects on plant growth and health. Specifically, we will conduct genomics-enabled, systematic forward genetic studies with natural genotypes of the model plant Arabidopsis thaliana and its outcrossing sister species A. lyrata. This will be complemented by experiments that will link diversity of microbial communities with that of the immune system in natural plant populations. The systematic understanding of forces that shape the distribution of immune gene alleles in the wild will have important implications for engineering disease resistance in crops, by helping to chose the best ensembles of resistance genes.

Keywords: plant immunity,fast-forward genetics,systems genetics,adaptation,microbiome
Multiscale modeling and simulation of biological and artificial locomotion at the micron scale: from metastatic tumor cells and unicellular swimmers to bioinspired microrobots (MICROMOTILITY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Products and process engineering
Countries involved: Italy
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-04-01
End date: 2020-03-31
Duration (months): 72.0
Total project cost (EUR): 1302270.0
EU funding (EUR): 1302270.0
Participants: 1
Project status: CLOSED

The project addresses the mechanical bases of cell motility by swimming and crawling, and the possibility of replicating the principles behind them in artificial systems. The goals are to elucidate some key mechanisms governing bio-locomotion. In particular, actin- based motility of crawling cells and motility by swimming of unicellular organisms will be studied both in general and with reference to concrete model systems. The study of biological examples of swimming and crawling motility will be used to produce a prototype of a micron-scale bio-inspired motile micro-robot exploiting the miniaturization that becomes possible from the extensive use of active materials. This is a multi-disciplinary research project. The themes arise from the Mechanics of Soft and Bio- logical Matter. The methods are those of Computational Engineering, and take advantage of innovative techniques from Applied Mathematics. The planned research activities rest on the development of new tools and methods in mathematical modeling, numerical simulation, data acquisition on biological systems, and on the construction of prototype devices. ***
Systematic Approach to Dissect the Interplay between Chromatin and Transcription (CHROMATINSYS)

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: Israel
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-01-01
End date: 2018-12-31
Duration (months): 60.0
Total project cost (EUR): 2396450.0
EU funding (EUR): 2396450.0
Participants: 1
Project status: CLOSED

Epigenetic mechanisms play an important role in regulating and maintaining the functionality of cells and have been implicated in a wide range of human diseases. Histone proteins that form the protein core of nucleosomes are subject to a bewildering array of covalent and structural modifications, which can repress, permit, or promote transcription. These modifications can be added and removed by specialized complexes that are recruited by other covalent modifications, by transcription factors, or by the transcriptional machinery. Advances in genomics led to comprehensive mapping of the ``epigenome'' in a range of tissues and organisms. These maps established the tight connection between histone modifications and transcription programs. These static charts, however, are less successful at uncovering the underlying mechanisms, logic, and function of histone modifications in establishing and maintaining transcriptional programs. Our premise is that we can answer these basic questions by observing the effect of genetic perturbations on the dynamics of both chromatin state and transcriptional activity. We aim to dissect the chromatin-transcription system in a systematic manner by building on our extensive experience in modeling and analysis, and a unique high-throughput experimental system we established in my lab. We plan to use the budding yeast model organism, which allows for efficient genetic and experimental manipulations. We will combine two technologies: (1) high-throughput measurements of single-cell transcriptional output using fluorescence reporters; and (2) high-throughput immunoprecipitation sequencing assays to map chromatin state. Measuring with these the dynamics of response to stimuli under different genetic backgrounds and using advanced stochastic network models, we will chart detailed mechanisms that are opaque to current approaches and elucidate the general principles that govern the interplay between chromatin and transcription.

Keywords: chromatin modifications,transcriptional regulation,systems biology,genetic interactions
The Radical Plasticity Thesis: How we learn to be conscious (RADICAL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: The Human Mind and its complexity
Countries involved: Belgium
Call:  (ERC-2013-ADG, 2013)
Start date: 2014-05-01
End date: 2019-10-31
Duration (months): 66.0
Total project cost (EUR): 2286316.0
EU funding (EUR): 2286316.0
Participants: 1
Project status: CLOSED

RADICAL explores the idea that consciousness is something that the brain learns to do rather than a static property of certain neural states vs. others. Here, considering that consciousness is extended both in space and in time, I adopt a resolutely dynamical perspective that mandates an experimental approach focused on change, at different time scales. I suggest that consciousness arises as a result of the brain's continuous attempts at predicting not only the consequences of its actions on the world and on other agents, but also the consequences of activity in one cerebral region on activity in other regions. By this account, the brain continuously and unconsciously learns to redescribe its own activity to itself, so developing systems of metarepresentations that characterise and qualify the target first order representations. Such learned redescriptions form the basis of conscious experience. Learning and plasticity are thus constitutive of consciousness. This is what I call the “Radical Plasticity Thesis”. In a sense, this is the enactive perspective, but turned both inwards and (further) outwards. Consciousness involves “signal detection on the mind”; the conscious mind is the brain's (non-conceptual, implicit) theory about itself. Theoretically, RADICAL offers the possibility of unifying Global Workspace Theory with higher-order Thought Theory by showing how the former can be built through mechanisms that flesh out the latter. Empirically, RADICAL aims at testing these ideas in three domains: (1) the perception action loop, (2) the self-other loop, and (3) the inner loop. 20 experiments leveraging behavioural experimentation, brain imaging, and computational modeling are proposed to test and further develop RADICAL. The overarching goal of the project is to characterize the computational principles that differentiate conscious from unconscious cognition, based on a bold, original, and innovative theory in which learning and plasticity play central roles.

Keywords: consciousness,learning,computational modeling,implicit and explicit learning,metacognition,cognitive development,autism,sensory substitution,neurofeebback