Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
The B cell memory program: cell fate determinants and functional diversity of B cell subsets (MEMO-B)

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-2009-AdG, 2009)
Start date: 2010-07-01
End date: 2015-06-30
Duration (months): 60.0
Total project cost (EUR): 1695980.0
EU funding (EUR): 1695980.0
Participants: 1
Project status: CLOSED

B cells are responsible for the humoral arm of the immune response and most successful vaccines in humans are antibody-based. Depending on the pathogen, specific B cell subsets are mobilized and a variety of innate, intermediate or adaptive responses are produced. In some cases these responses generate memory in anticipation of a re-encounter with the same pathogen. B cells can also present antigens to T cells, and enhance or suppress immune responses, depending in which T cell context they are primed. The present project aims to describe new innate-like and memory B cell subsets and to unravel the molecular switch allowing the differentiation and the long-term maintenance into the memory program. This will be done by combining approaches in both humans and mice, in order to reveal the analogies and the differences between these two immune systems. Our main specific aims are 1) to establish a reporter cell line that, by complementation with a cDNA library from human centrocytes and memory B cells, should allow the identification of a master gene able to trigger the memory program 2) to compare various antigenic and endogenous stimuli in terms of formation of various innate-like and memory subsets, using a mouse model that, by marking irreversibly B cells during an immune response, has allowed us to reveal new layers of B-cell memory 3) to study the endogenous and exogenous signals that support the development of marginal zone B cells in humans 4) to unravel the genes that govern long-term B cell memory, by isolating anti-vaccinia virus long-lived human memory B cells. The general ambition is to provide new insights into the complexity of the B cell compartment that should allow the improvement of B-cell targeted vaccination strategies.

Keywords: immunoglobulin,immune response,repertoire diversification
Conserved Non-Coding Sequences; function, variability and phenotypic consequences (HUCNC)

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: Switzerland
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-07-01
End date: 2015-06-30
Duration (months): 60.0
Total project cost (EUR): 2353920.0
EU funding (EUR): 2353920.0
Participants: 1
Project status: CLOSED

Comparative genomics revealed that ~5% of the human genome is conserved among mammals. This fraction is likely functional, and could harbor pathogenic mutations. We have shown (Nature 2002, Science 2003) that more than half of the constrained fraction of the genome consists of Conserved Non-Coding sequences (CNCs). Model organisms provided evidence for enhancer activity for a fraction of CNCs; in addition another fraction is part of large non-coding RNAs (lincRNA). However, the function of the majority of CNCs is unknown. Importantly, a few pathogenic mutations in CNCs have been associated with genetic disorders. We propose to i) perform functional analysis of CNCs, and ii) identify the spectrum of pathogenic CNC mutations in recognizable human phenotypes. The aims are: 1. Functional genomic connectivity of CNCs 1a. Use 4C in CNCs in various cell types and determine their physical genomic interactions. 1b. Perform targeted disruption of CNCs in cells and assess the functional outcomes. 2. Pathogenic variation of CNCs 2a. Assess the common variation in CNCs: i) common deletion/insertions in 350 samples by aCGH of all human CNCs; ii) common SNP/small indels using DNA selection and High Throughput Sequencing (HTS) of CNCs in 100 samples. 2b. Identify likely pathogenic mutations in developmental syndromes. Search for i) large deletions and duplications of CNCs using aCGH in 1500 samples with malformation syndromes, 1000 from spontaneous abortions, and 500 with X-linked mental retardation; and ii) point mutations in these samples by targeted HTS. The distinction between pathogenic and non-pathogenic variants is difficult, and we propose approaches to meet the challenge. 3. Genetic control (cis and trans eQTLs) of expression variation of CNC lincRNAs, using 200 samples.

Keywords: polymorphisms,pathogenic mutations,evolutionary conservation,gene expression variation,gwas,conserved non-coding sequences
Next Generation Molecular Ecology (NEXTGENMOLECOL)

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: Sweden
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-04-01
End date: 2015-09-30
Duration (months): 66.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

There is an immediate need to increase our understanding of the genetic basis for fitness differences in natural populations (Ellegren and Sheldon Nature 452:169-175, 2008). Fortunately, technological developments within genome research, notably the recent ability to retrieve massive amounts of DNA sequence data based on next generation sequencing , will make possible completely novel investigations of the link between genotypes and phenotypes in non-model organisms. With our background as major players in molecular ecology and evolutionary genomics of non-models for the last 15-20 years, we are excellently placed to take on a leading role in this process, developing a Next Generation Molecular Ecology . This research program will combine studies of candidate genes with large-scale gene expression analysis, several mapping approaches and comparative genomics to study the genetic basis of trait evolution in wild bird populations. First, we will search for and analyse loci involved with reproductive isolation and adaptive population divergence in a well-known system for speciation research the pied flycatcher and the collared flycatcher. A milestone of this program will be genome sequencing of the two flycatcher species. Second, we will track the genetic basis of behaviour using a unique breeding population of zebra finches and benefitting from the recently obtained genome sequence of this species. Third, we will identify the targets for adaptive evolution during avian evolution using comparative genomics. Overall, the program will be able to reveal the molecular genetic architecture behind phenotypic variation. The potential for scientific break-through in this interdisciplinary program should be significant.

Keywords: molecular ecology evolutionary genomics
Epigenetic challenges in centromere inheritance during the cell cycle (ECCENTRIC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: ERC Advanced Grant Interdisciplinary Panel
Countries involved: France
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-06-01
End date: 2015-12-31
Duration (months): 67.0
Total project cost (EUR): 2490483.0
EU funding (EUR): 2490483.0
Participants: 1
Project status: CLOSED

Studies concerning the mechanism of DNA replication have advanced our understanding of genetic transmission through multiple cell cycles. Recent work has shed light on possible means to ensure the stable transmission of information beyond just DNA and the concept of epigenetic inheritance has emerged. Considering chromatin-based information, key candidates have arisen as epigenetic marks including DNA and histone modifications, histone variants, non-histone chromatin proteins, nuclear RNA as well as higher-order chromatin organization. Thus, understanding the dynamics and stability of these marks following disruptive events during replication and repair and throughout the cell cycle becomes of critical importance for the maintenance of any given chromatin state. To approach these issues, we propose to study the maintenance of heterochromatin at centromeres, key chromosomal regions for the proper chromosome segregation. Our current goal is to access to the sophisticated mechanisms that have evolved in order to facilitate inheritance of epigenetic marks not only at the replication fork, but also at other stages of the cell cycle, during repair and development. Beyond inheritance of DNA methylation, understanding how inheritance of histone variants and their modifications can be controlled either coupled or not coupled to DNA replication will be a major focus of this project. Our studies will build on the expertise and tools developed over the years in a strategy that integrates molecular, cellular, and biochemical approaches. This will be combined with the use of new technologies to monitor cell cycle (Fucci), protein dynamics (SNAP-Tagging) together with single molecule analysis involving DNA and chromatin combing. We wish to define a possible framework for an understanding of both the stability and reversibility of epigenetic marks and their dynamics at centromeres. These lessons may teach us general principles of inheritance of epigenetic states.

Keywords: epigenetics,chromatin,development,cell-cycle,dna damage and repair,replication,histone variants,centromere
Understanding actions and intentions of others (COGSYSTEMS)

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: Italy
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-05-01
End date: 2015-04-30
Duration (months): 60.0
Total project cost (EUR): 1992000.0
EU funding (EUR): 1992000.0
Participants: 1
Project status: CLOSED

How do we understand the actions and intentions of others? Hereby we intend to address this issue by using a multidisciplinary approach. Our project is subdivided into four parts. In the first part we investigate the neural organization of monkey area F5, an area deeply involved in motor act understanding. By using a new set of electrodes we will describe the columnar organization of the area F5, establish the temporal relationships between the activity of F5 mirror and motor neurons, and correlate the activity of mirror neurons coding the observed motor acts in peripersonal and extrapersonal space with the activity of motor neurons in the same cortical column. In the second part we will assess the neural mechanism underlying the understanding of the intention of complex actions , i.e. actions formed by a sequence of two (or more) individual actions. The focus will be on the neurons located in ventrolateral prefrontal cortex, an area involved in the organization of high-order motor behavior. The rational of the experiment is that, while the organization of single actions and the understanding of intention behind them is function of parietal neurons, that of complex actions relies on the activity of the prefrontal lobe. In the third and fourth parts of the project we will delimit the cortical areas involved in understanding the goal (the what) and the intention (the why) of the observed actions in individuals with typical development (TD) and in children with autism and will establish the time relation between these two processes. Our hypothesis is that the chained organization of intentional motor acts is impaired in children with autism and this impairment prevents them from organizing normally their actions and from understanding others intentions.

Keywords: the aim of the project is to address the issue of action understanding with an interdisciplinary approach
Social Interaction and Entrainment using Music PeRformance Experimentation (SIEMPRE)

Framework: FP7 — Cooperation
Programme: Information and Communication Technologies
Destination: Future and emerging technologies
Action type: Collaborative project
Countries involved: Italy,Spain,United Kingdom,Switzerland,United States,Japan
Call:  (FP7-ICT-2009-C, 2009)
Start date: 2010-05-01
End date: 2013-06-30
Duration (months): 38.0
Total project cost (EUR): 2823477.0
EU funding (EUR): 2151500.0
Participants: 8
Project status: CLOSED

SIEMPRE develops research theoretical and methodological frameworks, computational models, and algorithms for the analysis of creative communication within groups of people, important also for future ICT (e.g. social media, on-line and mobile communities, web 2.0). Focus is on ensemble musical performance and audience experience, ideal testbed for the development of models and techniques for measuring creative social interaction in ecological framework. We focus on entrainment, emotional contagion, co-creation, each studied at two levels – between performers, between performer and audience - both during explicit communication process (e.g., between orchestra conductor and musicians) and during implicit synchronisation in emotionally intense experiences (joint music performance; audience live experience). Methodological framework will enable novel approaches to research challenges, including the integration in research teams of outstanding artists (funded by external projects). Expressive Movement, Audio, Physiological (eMAP) multi-layer multimodal features will be extracted from participants using real-time, synchronized, multi-modal feature extraction techniques, and are inputs for theoretical and computational models. Challenges and objectives: key factors driving interpersonal synchronisation of participants; identify specific roles inside the group (e.g., leadership, hierarchy); general principles concerning influence of individuals over others; factors that determine feelings of group cohesion or a sense of shared meaning; how eMAPs confirm the validity of reports by participants; how social context affects individual intrapersonal synchronization of eMAP and vice-versa; how emotion of the individual affects the collaborative creative product; neurophysiological foundations of creative group communication. A publicly available annotated database of behavioral data will be created. External US and Japan partners: Stanford Univ. and Waseda Univ.

Keywords: computational models of creative social behavior,synchronization,entrainment,emotion,multimodality
Sensing and Signalling in the Innate Immune Response, using Drosophila as a Model. (IMMUDROSO)

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-2009-AdG, 2009)
Start date: 2010-03-01
End date: 2015-02-28
Duration (months): 60.0
Total project cost (EUR): 2075000.0
EU funding (EUR): 2075000.0
Participants: 1
Project status: CLOSED

The project seeks to advance our knowledge of the innate immune system at two different but complementary levels, sensing and regulation of signalling. The first aim is centred on danger signals, and how they activate the immune system. We propose to use high-throughput RNA sequencing, molecular biology, fly and bacterial genetics to investigate the global network of genes and pathways that are involved in either endogenous (DNA and chromatin components) or exogenous (pathogen virulence factors) danger signal sensing. Drosophila is used here as a model system to analyse the complexities of host-pathogen interactions. As many bacteria use a common set of virulence factors to target different hosts, this work should lead to the identification of new defence genes and mechanisms in human. The second aim seeks to understand the mechanisms that fine-tune NF-ºB signalling in Drosophila and in mammals. NF-ºB mediates every aspect of inflammation and immune response through transcriptional programs that have to be orchestrated by yet unknown regulatory layers. The ability to effectively target inflammatory diseases for therapeutic intervention requires knowledge of the intricacies of these regulatory layers. First, we propose to characterize the molecular function of a new modulator of NF-ºB signalling that we have recently discovered, by using yeast two-hybrid screens, mass spectrometry and Drosophila genetics. In parallel, we propose to analyze the role of newly discovered and evolutionary conserved small RNAs in the regulation of the innate immune response in Drosophila. This exciting new area of research should lead to a better understanding of the control of immune reactions, one of the most important goals for medical research in the next decade.

Keywords: drosophila,infection,virulence factors
Decision-making and prefrontal executive function (FRONTEX)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: ERC Advanced Grant Interdisciplinary Panel
Countries involved: France
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-05-01
End date: 2016-04-30
Duration (months): 72.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

The prefrontal cortex (PFC) subserves decision-making and executive control, i.e. the ability to make decisions and to regulate behavior according to external events, mental models of situations, internal drives and subjective preferences. Our overall aim is to understand the functional architecture of the human PFC and computational mechanisms of PFC function. The PFC function is known to operate along three major dimensions, namely the affective, motivational and cognitive control of action subserved by the orbital, medial and lateral sectors of the PFC, respectively. In this project, our specific objectives are to solve the following three open issues of critical theoretical significance: (1) the functional organization of motivational control in the medial prefrontal cortex; (2) the mechanisms that enables the PFC to control the learning of representational sets required for cognitive control; (3) the functional interactions between the medial and lateral prefrontal cortex, i.e. the integration of motivational and cognitive control into a unitary decision-making and control system. We will address these theoretically and methodologically challenging issues by elaborating computational models that integrate learning and control mechanisms, and in relation to these models, by conducting functional magnetic resonance imaging experiments in healthy humans. The project is expected to significantly improve our knowledge of the human PFC function. This basic project has potential major implications especially in medicine, because alterations of the prefrontal function is observed in aging and most neuropsychiatric diseases, as well as in technology for developing artificial and robotics intelligence with human-like adaptive reasoning and decision-making abilities.

Keywords: humans,prefrontal cortex,fmri,computational modeling,executive control,reinforcement learning,decision-making
Generation of AAV-based, arrayed genetic libraries for in vivo functional selection: an innovative approach to identify secreted factors and microRNAs against degenerative disorders (FUNSEL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Italy
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-04-01
End date: 2015-03-31
Duration (months): 60.0
Total project cost (EUR): 1824000.0
EU funding (EUR): 1824000.0
Participants: 1
Project status: CLOSED

A foremost health problem stems from the burden of degenerative diseases, including heart failure, neurodegeneration, retinal degeneration and diabetes, essentially linked to the aging of the human population and the incapacity of post-mitotic tissues to undergo efficient repair. This is an ambitious, highly innovative project aimed at developing an in vivo selection procedure, based on gene transfer of two genetic libraries cloned into Adeno-Associated Virus (AAV)-based vectors, for the identification of novel secreted factors or microRNAs providing benefit against various degenerative diseases. Two arrayed libraries will be generated, one coding for ~1,300 cDNAs from the mouse secretome, the other for all known microRNAs (~800 genes). Pools of vectors from each library will be obtained with serotypes suitable for in vivo transduction of different organs. The vectors will be injected in a series of mouse models of degenerative disorders involving damage to cardiomyocytes,, neurodegeneration, retinal degeneration and loss of beta-cells in the pancreas. The degenerative conditions will drive the selection for secreted factors or miRNA putatively preventing cell apoptosis, enhancing residual cell function or, in the best possible scenario, promoting tissue regeneration. This in vivo selection approach, which is supported by very encouraging preliminary results, has never been attempted before and is rendered possible by the property of AAV vectors to be produced at high titers, infect tissues at high multiplicity, persist in the transduced cells for prolonged period of times and efficiently express their transgenes in vivo. In addition to its final goal of identifying novel biotherapeutics, the project entails the successful achievement of several intermediate objectives and is expected to extend both technology and knowledge beyond the state-of-the art.
Modulating cellular clearance to cure human disease (CLEAR)

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: Italy
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-03-01
End date: 2015-02-28
Duration (months): 60.0
Total project cost (EUR): 2100000.0
EU funding (EUR): 2100000.0
Participants: 1
Project status: CLOSED

Cellular clearance is a fundamental process required by all cells in all species. Important physiological processes, such as aging, and pathological mechanisms, such as neurodegeneration, are strictly dependent on cellular clearance. In eukaryotes, most of the cellular clearing processes occur in a specialized organelle, the lysosome. This project is based on a recent discovery, made in our laboratory, of a gene network, which we have named CLEAR, that controls lysosomal biogenesis and function and regulates cellular clearance. The specific goals of the project are: 1) the comprehensive characterization of the mechanisms underlying the CLEAR network, 2) the thorough understanding of CLEAR physiological function at the cellular and organism levels, 3) the development of strategies and tools to modulate cellular clearance, and 4) the implementation of proof-of-principle therapeutic studies based on the activation of the CLEAR network in murine models of human lysosomal storage disorders and of neurodegenerative diseases, such as Alzheimers s and Huntington s diseases. A combination of genomics, bioinformatics, systems biology, chemical genomics, cell biology, and mouse genetics approaches will be used to achieve these goals. Our goal is to develop tools to modulate cellular clearance and to use such tools to develop therapies to cure human disease. The potential medical relevance of this project is very high, particularly in the field of neurodegenerative disease. Therapies that prevent, ameliorate or delay neurodegeneration in these diseases would have a huge impact on human health.