Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
From gene to biomineral: Biosynthesis and application of sponge biosilica (BIOSILICA)

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: Germany
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2017-05-31
Duration (months): 72.0
Total project cost (EUR): 2183600.0
EU funding (EUR): 2183600.0
Participants: 1
Project status: CLOSED

During the last decade, the principles of biomineralization have increasingly attracted multidisciplinary scientific attention, not only because they touch the interface between the organic/inorganic world but also because they offer fascinating bioinspired solutions to notorious problems in the fields of biotechnology and medicine. However, only one group of animals has the necessary genetic/enzymatic toolkit to control biomineralization: siliceous sponges (Porifera). Based on his pioneering discoveries in poriferan molecular biology and physiological chemistry, the PI has brought biosilicification into the focus of basic and applied research. Through multiple trendsetting approaches the molecular key components for the enzymatic synthesis of polymorphic siliceous skeletal elements in sponges have been elucidated and characterized. Subsequently, they have been employed to synthesize innovative composite materials in vitro. Nonetheless, knowledge of the functional mechanisms involved remains sketchy and harnessing biosilicification, beyond the in vitro synthesis of amorphous nanocomposites, is still impossible. Using a unique blend of cutting-edge techniques in molecular/structural biology, biochemistry, bioengineering, and material sciences, the PI approaches for the first time a comprehensive analysis of natural biomineralization, from gene to biomineral to hierarchically ordered structures of increasing complexity. The groundbreaking discoveries expected will be of extreme importance for understanding poriferan biosilicification. Concurrently, they will contribute to the development of innovative nano-biotechnological and -medical approaches that aim to elicit novel (biogenous) optical waveguide fibers and self-repairing inorganic-organic bone substitution materials.

Keywords: molecular biomineralization,silica,silicatein,nanobiotechnology,biomedicine,sponges
BRain dEvelopment and Air polluTion ultrafine particles in scHool childrEn (BREATHE)

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: Spain,Spain
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-08-01
End date: 2016-07-31
Duration (months): 60.0
Total project cost (EUR): 2499230.0
EU funding (EUR): 2499230.0
Participants: 4
Project status: CLOSED

Traffic-related air pollution is an important environmental problem that may affect neurodevelopment. Ultrafine particles (UFP) translocate to the brains of experimental animals resulting in local proinflammatory overexpression. As the basic elements for thinking are acquired by developing brains during infancy and childhood, susceptibility may be elevated in early life. We postulate that traffic-related air pollution (particularly UFPs and metals/hydrocarbons content) impairs neurodevelopment in part via effects on frontal lobe maturation, likely increasing attention-deficit/hyperactivity disorder (ADHD). BREATHE objectives are to develop valid methods to measure children's personal UFP exposure and to develop valid neuroimaging methods to assess correlations between neurobehavior, neurostructural alterations and particle deposition in order to reveal how traffic pollution affects children¿s exposure to key contaminants and brain development, and identify susceptible subgroups. We have conducted general population birth cohort studies providing preliminary evidence of residential air pollution effects on prenatal growth and mental development. We aim to demonstrate short and long-term effects on neurodevelopment using innovative epidemiological methods interfaced with environmental chemistry and neuroimaging following 4000 children from 40 schools with contrasting high/low traffic exposure in six linked components involving: repeated psychometric tests, UFP exposure assessment using personal, school and home measurements, gene-environment interactions on inflammation, detoxification pathways and ADHD genome-wide-associated genes, neuroimaging (magnetic resonance imaging/spectroscopy) in ADHD/non-ADHD children, integrative causal modeling using mathematics, and replication in 2900 children with neurodevelopment followed from pregnancy. We believe the expected results will have worldwide global planning and policy implications.

Keywords: neurodepelopment,ultrafine particles,adhd,envirnomental chemistry,neuroimaging.
Ecological effects of light pollution (ECOLIGHT)

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: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2017-04-30
Duration (months): 72.0
Total project cost (EUR): 1600000.0
EU funding (EUR): 1600000.0
Participants: 1
Project status: CLOSED

The last 100 years have seen the dramatic spread of an evolutionarily unprecedented environmental change. Across huge areas, the spatial patterns and temporal cycles of light and dark that have previously remained approximately constant have been disrupted by the introduction of artificial night-time lights. This raises major concerns, given that light and dark provide critical resources and environmental conditions for organisms and play key roles in their physiology, growth, behaviour and reproduction, including the entrainment of internal biological clocks to local time. Indeed, it has long been recognised that light pollution of the night is likely to have profound consequences for the structure and functioning of populations and communities. Nonetheless, empirical studies of these effects remain wanting. This project will bring about a step change in understanding of the ecological consequences of night-time light pollution, addressing the principal question: How does the experimental manipulation of artificial night-time light influence population abundance, species composition and community structure? This will be answered using linked experimental studies. The results will have wide ramifications for understanding of the influences of rapid environmental change on population and community structure and of measures by which these can best be ameliorated.

Keywords: environmental change
Carbohydrate signals controlling nodulation (CASINO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Denmark
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2399127.0
EU funding (EUR): 2399127.0
Participants: 1
Project status: CLOSED

Mechanisms governing interaction between multicellular organisms and microbes are central for understanding pathogenesis, symbiosis and the function of ecosystems. We propose to address these mechanisms by pioneering an interdisciplinary approach for understanding cellular signalling, response processes and organ development. The challenge is to determine factors synchronising three processes, organogenesis, infection thread formation and bacterial infection, running in parallel to build a root nodule hosting symbiotic bacteria. We aim to exploit the unique possibilities for analysing endocytosis of bacteria in model legumes and to develop genomic, genetic and biological chemistry tools to break new ground in our understanding of carbohydrates in plant development and plant-microbe interaction. Surface exposed rhizobial polysaccharides play a crucial but poorly understood role in infection thread formation and rhizobial invasion resulting in endocytosis. We will undertake an integrated functional characterisation of receptor-ligand mechanisms mediating recognition of secreted polysaccharides and subsequent signal amplification. So far progress in this field has been limited by the complex nature of carbohydrate polymers, lack of a suitable experimental model system where both partners in an interaction could be manipulated and lack of corresponding methods for carbohydrate synthesis, analysis and interaction studies. In this context our legume model system and the discovery that the legume Nod-factor receptors recognise bacterial lipochitin-oligosaccharide signals at their LysM domains provides a new opportunity. Combined with advanced bioorganic chemistry and nanobioscience approaches this proposal will engage the above mentioned limitations.

Keywords: plant molecular genetics,structural biology,symbiosis
A phylogenetic and experimental approach to understand the evolution of microbiota (MICROBIOTAEVOLUTION)

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: Switzerland
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 2446004.0
EU funding (EUR): 2446004.0
Participants: 1
Project status: CLOSED

Microbial communities (=microbiota) associated with multicellular organisms play an important role in host nutrition and development. Advances in sequencing technology have revealed an unexpectedly high diversity of microbiota; these advances are not, however, matched by advances in our understanding of the evolutionary factors that structure microbiota. The goal of this proposal is to fill this knowledge gap. Evolutionary models developed for simple host-symbiont relationships have identified a number of factors that shape these relationships: mode of transmission (horizontal versus maternal transmission), host ranges and fitness effects for the host. Together these factors influence the role of selection among hosts and the role of selection within hosts (among microbes), the two levels of selection that are believed to shape host-symbiont coevolution. Here I intend to expand these models to host - microbiota interactions. My objectives are to use next-generation sequencing to conduct a comparative study of bacterial microbiota structure and to combine this work with experiments that explore the underlying evolutionary processes. I will focus on the crustacean family Daphniidae (mainly the genus Daphnia)¿a system ideally suited for studies in the field and laboratory. I will test hypotheses about the evolution of mutualism, virulence, cheating and coevolution, as well as test for the role of mode of transmission and host specificity. The analysis of host-microbiota associations will be conducted for entire microbiota and for stepwise simplified, but biologically meaningful subsets. Testing general models for the evolution of microbiota will have implications far beyond the chosen model system, ranging from ecology and evolution to agricultural sciences and medicine. The proposed study is innovative, significant and risk-taking and will combine skills in evolutionary biology, experimental design, bioinformatics and molecular biology.

Keywords: host-microbiota interactions,coevolution,mutualism,parasitism
DNA methylation in stem cells (METSTEM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Israel
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-04-01
End date: 2016-03-31
Duration (months): 60.0
Total project cost (EUR): 1941930.0
EU funding (EUR): 1941930.0
Participants: 1
Project status: CLOSED

Embryonic and adult stem cells constitute an important component of biology by providing a pool of pluri- and multi-potent cells that supply a variety of different cell lineages. Little is known about the mechanisms involved in establishing and maintaining cell ¿stemness,¿ but it is most likely controlled by epigenetic signals such as DNA methylation. This proposal aims to understand these mechanisms and decipher the molecular logic used to program this plasticity. We have developed a new strategy for studying the ¿DNA methylation potential¿ of any cell type throughout normal development. This utilizes a unique set of transgenic vectors programmed to detect both de novo methylation as well as the ability to protect CpG islands, and will, for the first time, allow one to evaluate the role of demethylation in normal stem cells and during reprogramming. This will be done using a new technique called ¿reverse epigenetics¿. Preliminary studies indicate that embryonic stem cells differentiated in vitro undergo extensive aberrant methylation that does not reflect the normal pattern of methylation found in vivo. This artifact may be responsible for our inability to attain efficient differentiation in culture and may generate cells that are unhealthy and prone to cancer. We will characterize the causes of this phenomenon and decipher its underlying mechanism. This research should lead to the development of improved methods for tissue generation in vitro. One of the most basic properties of adult stem cells is their ability to undergo asymmetric cell division that is often associated with unequal segregation of DNA. This mechanism is one of the most elemental, yet mysterious, aspects of stem cell biology. We have developed a completely new molecular model for this process that is based on the idea that non-symmetric DNA methylation serves as a strand-specific marker, and it is very likely that this will enable us to finally decipher this basic aspect of stem cells.

Keywords: gene regulation,stability,programming,dna segregation
Epigenetic Disruption of Non-Coding RNAs in Human Cancer (EPINORC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Spain
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-04-01
End date: 2016-03-31
Duration (months): 60.0
Total project cost (EUR): 2497240.0
EU funding (EUR): 2497240.0
Participants: 1
Project status: CLOSED

In recent years, my laboratory, as well as others, have established the observation that epigenetic disruption, particularly in the DNA methylation and histone modification patterns, contributes to the initiation and progression of human tumors (Esteller, Nat Rev Genet 2007; Esteller, N Engl J Med 2008; Esteller, Nat Rev Biotech, In Press, 2010). Even more recently, it has been recognized that microRNAs, small non-coding RNAs that are thought to regulate gene expression by sequence-specific base pairing in mRNA targets, also play a key role in the biology of the cell, and that they can also have an impact in the development of many diseases, including cancer (le Sage and Agami, 2006; Blenkiron and Miska, 2007). However, there is little understanding about epigenetic modifications that might regulate the activity of microRNAs and other non-coding RNAs (ncRNAs), such as long non-coding RNAs (lncRNAs), Piwi-interacting RNAs (piRNAs), small-interfering RNAs (siRNAs), transcribed ultraconserved regions (T-UCRs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), long interspersed ncRNAs (lincRNAs), promoter-associated RNAs (PASRs and PALRs) and terminator-associated sRNAs (TASRs) (Calin et al., 2007; Mercer, et al., 2009; Ghildiyal & Zamore, 2009; Jacquier, 2009). Our ignorance in this respect is even more significant if we consider these questions in the domain of cancer. Making best use of our expertise in several of these fields, my group will tackle the study of the epigenetic modifications that regulate ncRNA expression and how the DNA methylation and histone modifications profiles of these loci might become distorted in human cancer. These findings could have profound consequences not only in the understading of tumor biology, but in the design of better molecular staging, diagnosis and treatments of human malignancies.

Keywords: cancer,epigenetics,dna methylation,histone modifications,non-coding rnas
Dreaming of no more renal dialysis: how self-derived tissue and cells can replace renal function (RESET)

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-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2493000.0
EU funding (EUR): 2493000.0
Participants: 1
Project status: CLOSED

For chronic kidney diseases there is little chance that the vast majority of the world¿s population will have access to renal replacement therapy with dialysis. There is yet no adequate alternative with curative intent than allo-transplantation. This approach is seriously impaired by eventually limited graft survival and by the scarce availability of donors. We propose an innovative strategy that would help to simultaneously overwhelm the reduced access to dialysis, the need for organs for transplantation, the avoidance of patient exposure to immunosuppressants. The overall focus is based on the idea of generating new kidneys by tissue engineering technologies starting from a whole-kidney scaffold with intact three-dimensional geometry and vasculature created by de-cellularization of a kidney harvested from the patient with progressive chronic kidney disease (CKD). Repopulation of the kidney scaffold could be achieved with patient-specific induced pluripotent stem (iPS) cells generated by reprogramming to a pluripotent status of somatic cells. After regeneration, the kidney will be transplanted in the same patient. Thereafter, the same procedures will be repeated with the contralateral native injured kidney, after in vivo assessment of the proper functional performance of the newly generated transplanted organ. This goal will be pursued through the three steps introductory to the development of the best strategy for translating the proposed frontier research to patients with CKD: 1.Create an intact whole-kidney scaffold by de-cellularization of a rodent kidney and validate the procedure with a human kidney. 2. Attempt to reconstruct the organ by reseeding the rodent and human whole-kidney scaffolds with iPS cells generated by reprogramming adult dermal fibroblasts to a pluripotent status. 3. Deeply characterize the function of the new rodent and human kidneys by in vivo and in vitro techniques.

Keywords: chronic renal diseases,inducible pluripotent stem cells,de-cellularized kidney scaffold,kidney reconstruction
MAL: an actin-regulated SRF transcriptional coactivator (ACTINONSRF)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-10-01
End date: 2017-09-30
Duration (months): 72.0
Total project cost (EUR): 1889995.0
EU funding (EUR): 1889995.0
Participants: 2
Project status: CLOSED

MAL: an actin-regulated SRF transcriptional coactivator Recent years have seen a revitalised interest in the role of actin in nuclear processes, but the molecular mechanisms involved remain largely unexplored. We will elucidate the molecular basis for the actin-based control of the SRF transcriptional coactivator, MAL. SRF controls transcription through two families of coactivators, the actin-binding MRTFs (MAL, Mkl2), which couple its activity to cytoskeletal dynamics, and the ERK-regulated TCFs (Elk-1, SAP-1, Net). MAL subcellular localisation and transcriptional activity responds to signal-induced changes in G-actin concentration, which are sensed by its actin-binding N-terminal RPEL domain. Members of a second family of RPEL proteins, the Phactrs, also exhibit actin-regulated nucleocytoplasmic shuttling. The proposal addresses the following novel features of actin biology: ¿ Actin as a transcriptional regulator ¿ Actin as a signalling molecule ¿ Actin-binding proteins as targets for regulation by actin, rather than regulators of actin function We will analyse the sequences and proteins involved in actin-regulated nucleocytoplasmic shuttling, using structural biology and biochemistry to analyse its control by changes in actin-RPEL domain interactions. We will characterise the dynamics of shuttling, and develop reporters for changes in actin-MAL interaction for analysis of pathway activation in vivo. We will identify genes controlling MAL itself, and the balance between the nuclear and cytoplasmic actin pools. The mechanism by which actin represses transcriptional activation by MAL in the nucleus, and its relation to MAL phosphorylation, will be elucidated. Finally, we will map MRTF and TCF cofactor recruitment to SRF targets on a genome-wide scale, and identify the steps in transcription controlled by actin-MAL interaction.

Keywords: actin,mrtf,rho,transcription