Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Role of Class IIa Histone deacetylases in hematopoietic cell differentiation (HDAC HEMATOPOIESIS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2007-09-01
End date: 2011-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 2
Project status: CLOSED

Chromatin, the higher order structure of DNA and protein, forms a barrier for gene transcription. Modification of histones, a major component of the chromatin, is a critical mechanism by which the barrier is regulated. An important modification, which is thought to activate transcription, is the acetylation of histones. Regulation of histones acetylation is performed by the antagonistic activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Mammalian HDACs are divided into three distinct classes based on their homology to yeast proteins. Class I HDACs (HDAC1, 2, 3 and 8), Class II HDACs, which are subdivided into two families, Class IIa (HDAC4, 5, 7 and 9) and Class IIb (HDAC6 and 10) and Class III HDACs, also named sirtuins, which comprises Sirt1, 2, 3, 4, 5, 6 and 7. In contrast to other HDACs, Class IIa HDACs are expressed in a tissue specific manner and have been shown to play an important role in cell differentiation. The hematopoietic system is a complex and interesting model of cell commitment and differentiation. Hematopoietic lineages are specified by lineage-restricted transcription factors that result in a distinct gene expression pattern. However, little is known about the role of chromatin modifying enzymes in the hematopoietic system. It has been shown that HDAC5 and HDAC9 are expressed in hematopoietic cells. However, their role in commitment of hematopoietic cells has never been investigated. Here, I propose to study the role of HDAC5 and HDAC9 in lineage commitment of hematopoietic cells. By using a genomic approach, as well as, knock out and trangenic mouse models, I will elucidate the lineage compartment where they are expressed, the specific target genes repressed by both proteins and their role in hematopoietic cell differentiation. The elucidation of the molecular mechanisms involved in the lineage commitment of hematopoietic stem cells will suppose an important advance in regenerative medicine.

Keywords: histone deacetylases,chromatin,hematopoiesis,lineage commitment,stem cells
A systems-level understanding of the novel principle in early mammalian development (MAMMALIANDEVELOPMENT)

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-2007-StG, 2007)
Start date: 2008-07-01
End date: 2013-12-31
Duration (months): 66.0
Total project cost (EUR): 1150000.0
EU funding (EUR): 1150000.0
Participants: 2
Project status: CLOSED

Early mammalian development is a unique process creating an extraembryonic structure. Despite its importance for understanding mammalian development and direct relevance to clinical practice, the mechanism underlying polarity establishment in the mammalian embryo has long been elusive. One of the major obstacles is the lack of description in molecular terms, since very few genes are known to specify the early lineages. Our recent studies provide a conceptual basis, suggesting that the mechanism is unique to mammals. The primary aim of this proposal is to elucidate the molecular program and the novel principle of early mammalian development at a systems level. To comprehensively identify molecules involved in early mouse development, we will conduct two complementary screens. One is a lentivirus-based promoter-trap screen: Venus-reporter is to be expressed under the endogenous control of the integrated genomic locus, which will be monitored using our live-embryo imaging system. Embryos showing a differential expression pattern will be selected for further analysis. As a complementary approach, single-blastomere-derived cRNAs are generated from embryos of various stages by the recently developed single-cell cRNA amplification method, followed by microarray analysis to statistically identify gene clusters differentially expressed in specific blastomeres. Function of the genes identified in two screens will be examined by RNAi and maternally conditional KO. Finally, the knowledge will be integrated into our computer simulation that successfully reconstitutes blastocyst morphogenesis. In the long term, the obtained tools (markers and Venus-trap lines) will provide a basis for functional siRNA screen. Genetic screen in early mouse embryos has never been achieved. Though we anticipate certain difficulties, we are confident that with the relevant expertise of collaborators and ourselves, these can be resolved and a substantial advance will be made in this important area.

Keywords: early mammalian development embryonic patterning live-imaging gene-trap
4C technology: uncovering the multi-dimensional structure of the genome (4C)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Genetics,Genomics,Bioinformatics and Systems Biology
Countries involved: Netherlands
Call:  (ERC-2007-StG, 2007)
Start date: 2008-09-01
End date: 2013-08-31
Duration (months): 60.0
Total project cost (EUR): 1225000.0
EU funding (EUR): 1225000.0
Participants: 1
Project status: CLOSED

The architecture of DNA in the cell nucleus is an emerging epigenetic key contributor to genome function. We recently developed 4C technology, a high-throughput technique that combines state-of-the-art 3C technology with tailored micro-arrays to uniquely allow for an unbiased genome-wide search for DNA loci that interact in the nuclear space. Based on 4C technology, we were the first to provide a comprehensive overview of long-range DNA contacts of selected loci. The data showed that active and inactive chromatin domains contact many distinct regions within and between chromosomes and genes switch long-range DNA contacts in relation to their expression status. 4C technology not only allows investigating the three-dimensional structure of DNA in the nucleus, it also accurately reconstructs at least 10 megabases of the one-dimensional chromosome sequence map around the target sequence. Changes in this physical map as a result of genomic rearrangements are therefore identified by 4C technology. We recently demonstrated that 4C detects deletions, balanced inversions and translocations in patient samples at a resolution (~7kb) that allowed immediate sequencing of the breakpoints. Excitingly, 4C technology therefore offers the first high-resolution genomic approach that can identify both balanced and unbalanced genomic rearrangements. 4C is expected to become an important tool in clinical diagnosis and prognosis. Key objectives of this proposal are: 1. Explore the functional significance of DNA folding in the nucleus by systematically applying 4C technology to differentially expressed gene loci. 2. Adapt 4C technology such that it allows for massive parallel analysis of DNA interactions between regulatory elements and gene promoters. This method would greatly facilitate the identification of functionally relevant DNA elements in the genome. 3. Develop 4C technology into a clinical diagnostic tool for the accurate detection of balanced and unbalanced rearrangements.

Keywords: 4c technology,nuclear organisation,genomic rearrangements,chromosome folding
Characterisation of a novel state of matter: The Quark-Gluon Plasma (QGP)

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: Netherlands
Call:  (ERC-2007-StG, 2007)
Start date: 2008-09-01
End date: 2013-08-31
Duration (months): 60.0
Total project cost (EUR): 850000.0
EU funding (EUR): 850000.0
Participants: 1
Project status: CLOSED

I propose to explore the properties of a novel state of matter, the Quark-Gluon Plasma (QGP), created by colliding atomic nuclei at the highest energy ever reached using triggered particle correlations. The QGP is predicted by the fundamental theory of strong interactions and is characterized by an equilibrated system of free quarks and gluons that are the constituents of atomic nuclei. My investigation of the QGP properties will give unique insights into the development of the early universe and the properties of matter under extreme conditions. Among other results, particle correlation measurements have revealed first compelling evidence for the existence of the QGP state. Due to the limited sensitivity of the used probes, the conclusions are to some extent qualitative rather than quantitative. To get a deeper understanding of the mechanisms at work I propose to study heavy-quark correlations and their in-medium modification in collisions of heavy nuclei by combining the information from different detection systems. I have verified the feasibility of this measurement at lower energies. I am currently one of the world’s experts in measuring heavy-quark correlations and I propose to perform such a measurement at the forefront particle accelerator, the Large Hadron Collider, located at the European Laboratory for Particle Physics CERN. My investigation will be done utilizing the dedicated ALICE (A Large Ion Collider Experiment) detector, which is most suited for measurements in heavy-ion collisions. I would like to do my project with one Postdoc and one Ph.D. student during a period of five years. My research team will be embedded in one of the leading institutes in the field of heavy-ion physics which provided a crucial hardware component to the ALICE experiment. My expertise and the outstanding working environment will guarantee high quality in performing my key measurement. The ALICE experiment will be the place of new discoveries.

Keywords: quark-gluon plasma,large hadron collider at cern,alice experiment
Subretinal Microglia accumulation play a decisive role in the development of Age-related Macular Degeneration (MICROGLIA AND AMD)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: France
Call:  (ERC-2007-StG, 2007)
Start date: 2008-09-01
End date: 2013-08-31
Duration (months): 60.0
Total project cost (EUR): 1560000.0
EU funding (EUR): 1560000.0
Participants: 1
Project status: CLOSED

Age-related macular degeneration (AMD) is the leading cause of vision loss in the Europe. New anti-angiogenic therapies of AMD do not treat the neurodegenerative aspect of AMD. Recent evidence suggests an implication of inflammatory mediators in AMD. We have focused our interest on the potential role of chemokines (Ch) and microglial cells (MC) in this condition. Our data concerning the chemokine receptor (CR) CX3CR1, indicates that (i) CR are expressed on MCs in human and mice; (ii) CR-positive MC accumulate in affected areas of the macula in human AMD, (iii) CX3CR1 deficient mice develop age dependent subretinal MC accumulation, Drusen formation, retinal degeneration and exacerbated neovascularization, similarly to AMD. Our data suggests an important role of subretinal MC accumulation in the development of AMD. We hypothesize that (1) function altering polymorphisms in genes of Ch pathways are associated with AMD, that (2) this pathway dysfunction leads to MC accumulate in the subretinal space with age and (3) the consequential prolonged MC presence in the subretinal space leads to cardinal features of AMD (Drusen, retinal degeneration, neovascularization). Therefore we believe that decreasing subretinal MCs or interfering with their neurotoxic and angiogenic factors will inhibit AMD development. Our specific aim is to study (1) polymorphisms of Ch pathways in AMD and controls, (2) determine the Ch pathways involved in the recruitment and accumulation of MCs to the subretinal space, (3) determine the implication of MC in Drusen formation, retinal degeneration and neovascularization and characterize the implicated molecular mediators and (4) test the identified mediators of microglial cell neurotoxicity and angiogenicity as drug targets in AMD models. The aim of this work, from clinical polymorphism studies to transgenic mouse models, is to propose new mechanisms in the pathogenesis of AMD and to develop novel therapeutic strategies for the treatment of AMD.

Keywords: age related macular degeneration,chemokines,microglia,neovascularization,retinal degeneration
Bioactive resorbable scaffolds for drug delivery in bone tissue engineering (BIORESS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: European Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Italy
Call:  (FP7-PEOPLE-2007-2-2-ERG, 2007)
Start date: 2008-01-15
End date: 2011-01-14
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

Bone tissue engineering is a new research area with clinical applications in the replacement of diseased or damaged bone tissues. The challenge of tissue engineering is to develop a suitable bone scaffold with sufficient porosity and mechanical strength to allow a good integration with the surrounding tissues. Bioactive resorbable scaffolds that combine the characteristics of materials for bone tissue engineering with the one of drug delivery systems, are an innovative approach in materials engineering field. By implantation of these materials in the desired body location, they will release the therapeutic agent, improving the efficiency of the clinical treatment. Due to their bioactivity, they can be used as bone substitute, increasing the bone integration (osteointegration). Due to their biodegradation, they can control the kinetics releasing of the active agent. The scaffold porosity controls the amount of the therapeutic agent that can be incorporated. Therefore, the aim of this project is the development, characterisation and in vitro experimentation of novel macroporous scaffolds with highly interconnected porosity and controlled biodegradability for drug delivery in bone tissue engineering. Optimisation of the scaffold structure is essential to achieve both adequate mechanical and biological response in clinical applications. The macro and microstructure of the porous scaffolds will be investigated. Cell culturing experiments will be carried out to assess the biological behaviour of these materials. The scaffold surface will be functionalized in order to bind specific macromolecules (proteins, antibiotics, growth factors etc.) for drug delivery. The dependence of the drug delivery profiles on the scaffold biodegradation will be studied in vitro. We expect that these innovative materials will be useful as delivery systems for cells and biological molecules in bone tissue engineering applications.

Keywords: biomaterial engineering,biomedical materials,biomedical engineering,resorbable,macroporous,scaffolds,bioactivity,functionalisation,drug delivery,bone tissue engineering.
On the other hand: the linguistic impact of having two symmetrical articulators in sign language (ON THE OTHER HAND)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Environment and society
Countries involved: Netherlands
Call:  (ERC-2007-StG, 2007)
Start date: 2008-10-01
End date: 2013-09-30
Duration (months): 60.0
Total project cost (EUR): 500000.0
EU funding (EUR): 500000.0
Participants: 1
Project status: CLOSED

Deaf people communicate with two hands. Hearing people communicate with only one mouth. What are the implications of this difference for our view of human language? The proposed research aims to approach this central issue by addressing a number of new and concrete questions, using highly innovative methods. Linguistic models are generally based on the fact that spoken language structures are linear and hierarchically structured. The symmetry of the two hands in signed languages makes room for abundant simultaneity, even though our motor system imposes severe constraints on the independent action of the two hands. We know that deaf people rarely utter two different sentences at the same time (one with the left and one with the right hand), but there are indications that from below the level of single signs up to the structuring of discourse, the two hands contribute to communication in a fashion unparalleled in spoken languages. The two hands can be mere copies of each other, but in many well-described cases the second hand is not redundant and both hands can perform independent linguistic functions. This proposal focuses on three questions that target different components in Nederlandse Gebarentaal (NGT, Sign Language of the Netherlands): discourse, syntax, and phonology. 1. What kind of information does a second hand contribute to signed communication in longer utterances (discourse)? 2. Which types of utterances in which a second hand occurs (subordination, coordination, parenthesis, apposition) can be distinguished in signed sentences? 3. What are the constraints on the one-handed articulation of two-handed signs, which is often necessary to create simultaneous constructions? To answer these questions, the most recent technical possibilities will be employed. Our corpus of NGT (Sign Language of the Netherlands), one of the first and largest digital sign language corpora in the world, will serve as the central resource for addressing all questions.

Keywords: sign language,phonetics,discourse
Role and development of the corpus callosum for the interhemispheric transfer of visual motion (DIRCALLOSDVPT)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2008-01-01
End date: 2011-07-03
Duration (months): 36.0
Total project cost (EUR): 75000.0
EU funding (EUR): 75000.0
Participants: 1
Project status: CLOSED

Our perception of the world is mainly dynamic. In order to interact adequately with the environment, our brain must analyze rapidly and efficiently various kind of motion present in the visual world, including complex motions such as the optic flow induced by our own movements. The primary visual cortex, through its direction-selective cells, is the first cortical step toward such integration. Each hemifield is analyzed by one hemisphere, and the corpus callosum is thought to link these two representations into a single dynamic scene. Using cat as a model animal and optical imaging as a technique, the goal of this project is to elucidate the role of the corpus callosum in the interhemispheric transfer of visual motion. Recent experiments have however challenged a limited view of the primary visual cortex for the processing of motion: the primary visual cortex was recently implicated in the processing of illusionary motion, optic flow induced by self-motion, composition of plaids. We plan to perform series of experiments on cats of various ages, from eye-opening to adult cats, with the use of different stimulation paradigms. All together, these experiments will provide new knowledge about how the corpus callosum can provide a substrate for the interhemispheric transfer of different types of visual motion, and how this involvment develops with age.

Keywords: neurophysiology
The impact of mass media on public policy (MEDIA AND POLICY)

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: Sweden
Call:  (ERC-2007-StG, 2007)
Start date: 2008-09-01
End date: 2014-08-31
Duration (months): 72.0
Total project cost (EUR): 799945.0
EU funding (EUR): 799945.0
Participants: 1
Project status: CLOSED

This project will study political economics issues, that is, how public policies are influenced by political considerations. The emphasis is on the mass media's role in shaping government policies. A smaller part will also analyze how different political institutions and economic outcomes influence policy and the impact of extreme weather events. The project will mainly be empirical, using statistical methods with a focus on identifying causal effects, rather than correlations. The study of media effects will analyze the political impact of having a press actively covering politics. This is an important issue, largely unanswered because the presence of an active press is endogenous to things like corruption and voter information. We will address this question in the special case of media coverage of US Congressional elections. To identify the effect of news, we will use the fact that the amount of coverage is driven to a large extent by the coincidental match between media markets and congressional districts. We intend to analyze the effect of active press coverage on, (i) voter information, (ii) politicians actions, and (iii) federal funds per capita. The project will also investigate how political institutions and economic outcomes influences the health impacts (such as mortality among old and infants) of weather extremes. Historical weather data at a very detailed geographical level will be combined with socio-economic data in a panel (longitudinal) form. This is joint work with meteorologists who will construct historical weather data at fine grids across the globe. The part dealing with structural political economics aims to develop a framework for investigating the effects of institutions on economic policy. In existing work, there is a disconnect between the theoretical modelling and empirical applications. The aim is to close this gap.

Keywords: mass media,political economics,public policy