Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
The genomic and transcriptomic locus of sex-specific selection in birds (AVIAN DIMORPHISM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: United Kingdom,United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2016-07-31
Duration (months): 67.0
Total project cost (EUR): 1350804.0
EU funding (EUR): 1350804.0
Participants: 2
Project status: CLOSED

It has long been understood that genes contribute to phenotypes that are then the basis of selection. However, the nature and process of this relationship remains largely theoretical, and the relative contribution of change in gene expression and coding sequence to phenotypic diversification is unclear. The aim of this proposal is to fuse information about sexually dimorphic phenotypes, the mating systems and sexually antagonistic selective agents that shape sexual dimorphism, and the sex-biased gene expression patterns that encode sexual dimorphisms, in order to create a cohesive integrated understanding of the relationship between evolution, the genome, and the animal form. The primary approach of this project is to harnesses emergent DNA sequencing technologies in order to measure evolutionary change in gene expression and coding sequence in response to different sex-specific selection regimes in a clade of birds with divergent mating systems. Sex-specific selection pressures arise in large part as a consequence of mating system, however males and females share nearly identical genomes, especially in the vertebrates where the sex chromosomes house very small proportions of the overall transcriptome. This single shared genome creates sex-specific phenotypes via different gene expression levels in females and males, and these sex-biased genes connect sexual dimorphisms, and the sexually antagonistic selection pressures that shape them, with the regions of the genome that encode them. The Galloanserae (fowl and waterfowl) will be used to in the proposed project, as this clade combines the necessary requirements of both variation in mating systems and a well-conserved reference genome (chicken). The study species selected from within the Galloanserae for the proposal exhibit a range of sexual dimorphism and sperm competition, and this will be exploited with next generation (454 and Illumina) genomic and transcriptomic data to study the gene expression patterns that underlie sexual dimorphisms, and the evolutionary pressures acting on them. This work will be complemented by the development of mathematical models of sex-specific evolution that will be tested against the gene expression and gene sequence data in order to understand the mechanisms by which sex-specific selection regimes, arising largely from mating systems, shape the phenotype via the genome.

Keywords: sexual selection,mating systems,comparative genomics
DNA Adduct Molecular Probes: Elucidating the Diet-Cancer Connection at Chemical Resolution (DNA-AMP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Switzerland
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-09-01
End date: 2015-08-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Bulky DNA adducts formed from chemical carcinogens dictate structure, reactivity, and mechanism of chemical-biological reactions; therefore, their identification is central to evaluating and mitigating cancer risk. Natural food components, or others associated with certain food preparations or metabolic conversions, initiate potentially damaging genetic mutations after forming DNA adducts, which contribute critically to carcinogenesis, despite the fact that they are typically repaired biochemically and they are formed at extremely low levels. This situation places significant limitations on our ability to understand the role of formation, repair, and mutagenesis on the basis of the complex DNA reactivity profiles of food components. The long-term goals of this research are to contribute basic knowledge and advanced experimental tools required to understand, on the basis of chemical structure, the contributions of chronic, potentially adverse, dietary chemical carcinogen exposure to cancer development. It is proposed that a new class of synthetic nucleosides, devised on the basis of preliminary discoveries made in the independent laboratory of the applicant, will serve as molecular probes for bulky DNA adducts and can be effectively used to study and AMPlify, i.e. as a sensitive diagnostic tool, low levels of chemically-specific modes of DNA damage. The proposed research is a chemical biology-based approach to the study of carcinogenesis. Experiments involve chemical synthesis, thermodynamic and kinetic characterization DNA-DNA and enzyme-DNA interactions, and nanoparticle-based molecular probes. The proposal describes a potentially ground-breaking approach for profiling the biological reactivities of chemical carcinogens, and we expect to gain fundamental knowledge and chemical tools that can contribute to the prevention of diseases influenced by gene-environment interactions.

Keywords: chemical biology
Differentiation of pro-inflammatory T cell subsets in vivo (T_CELL(S)_DIFFER)

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: Portugal
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2015-06-30
Duration (months): 55.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Our understanding of T cell differentiation impacts on vaccine development and on the treatment of (auto) immune disorders. T cells are key players in inflammation, a crucial component of the immune response to pathogens that causes severe damage to the host when uncontrolled. The cytokines Interferon-(IFN-) and Interleukin-17 (IL-17) are critical mediators of the proinflammatory activity of T cells usually designated as “T helper 1” (Th1) and Th17, respectively. Here we propose to investigate the contribution of all T cell lineages - CD4+ and CD8+ cells, and NKT cells – to global Th1 or Th17 immune responses, using various tools including a IFN-/IL-17 double reporter mouse. Importantly, we will study Th1/ Th17 differentiation in vivo, inmodels of infection with Plasmodium berghei or Mycobacterium tuberculosis. We will analyse theindividual and combined contributions of the distinct T cell subsets, their cellular interactions andpotential interdependence in lymphoid organs and in target organs of infection. We further envisage a molecular understanding of how innate (and NKT) and adaptive (CD4+ and CD8+) T cell subsets acquire their respective capacities to produce IFN-or IL-17 in vivo. We will dissect (pre-/ post-) transcriptional mechanisms of regulation of Ifng and Il17 expression in the various T cell subsets, ultimately at the single-cell level. We aim at characterizing networks of transcription factors and microRNAs that regulate Th1/ Th17 differentiation either in all or in specific T cell subsets. We are particularly interested in addressing the constitutive expression of IFN-or IL-17 by innate T lymphocytes, which is set up in the thymus. We will define the molecular components of this “developmental pre-programming” of and NKT cells in comparison with the mechanisms of peripheral induction of CD4+ Th1/ Th17 cell differentiation upon infection. By contrast to the generalized focus on CD4+ T cells, this project will consider Th1/ Th17 differentiation of all T cell lineages and their in vivo contributions to relevant models of infection. I believe this holistic view of organism-based immune parameters and their underlying molecular mechanisms, down to the single-cell level, will significantly advance our understanding of how the Immune System works.

Keywords: lymphocytes,t cells,cytokines,regulation of gene expression
Understanding epigenetic mechanisms of complex genome editing in eukaryotes. (EPIGENOME)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Switzerland
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

The scientific goal of this proposal is to contribute to our understanding of RNA-mediated epigenetic mechanisms of genome regulation in eukaryotes. Choosing ciliated protozoa as model organisms gives a wonderful opportunity to study the incredibly complex epigenetic mechanism of programming large-scale developmental rearrangements of the genome. This involves extensive rearrangements of the germline DNA, including elimination of up to 95% of the genome. The massive DNA rearrangement makes ciliates the perfect model organism to study this aspect of germline-soma differentiation. This process is proposed to be regulated by an RNA-mediated homology-dependent comparison of the germline and somatic genomes. Ciliate’s genomic subtraction is one of the most fascinating examples of the use of RNA-mediated epigenetic regulation, and of a specialized RNA interference pathway, to convey non-Mendelian inheritance in eukaryotes. The ‘genome scanning’ model raises many interesting questions, which are also relevant to other RNA-mediated regulation systems. One of the most intriguing is a ‘thermodynamic’ problem: the model assumes that a very complex population of small RNAs representing the entire germline genome can be compared to longer transcripts representing the entire rearranged maternal genome, resulting in the efficient selection of germline-specific scnRNAs, which are able to target DNA deletions in the developing nucleus. How is it possible that the truly enormous number of pairing interactions implied can occur in such a short time, just a few hours? RNA-RNA pairing interactions would probably have to be assisted by a dedicated molecular machinery. This proposal focuses on characterizing proteins and RNAs that can orchestrate the massive genome rearrangements in ciliates.

Keywords: genome rearrangements,non-coding rna
Neural circuit function in the retina of mice and humans (CELLTYPESANDCIRCUITS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Switzerland
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1499000.0
EU funding (EUR): 1499000.0
Participants: 2
Project status: CLOSED

The mammalian brain is assembled from thousands of neuronal cell types that are organized into distinct circuits to perform behaviourally relevant computations. To gain mechanistic insights about brain function and to treat specific diseases of the nervous system it is crucial to understand what these local circuits are computing and how they achieve these computations. By examining the structure and function of a few genetically identified and experimentally accessible neural circuits we plan to address fundamental questions about the functional architecture of neural circuits. First, are cell types assigned to a unique functional circuit with a well-defined function or do they participate in multiple circuits (multitasking cell types), adjusting their role depending on the state of these circuits? Second, does a neural circuit perform a single computation or depending on the information content of its inputs can it carry out radically different functions? Third, how, among the large number of other cell types, do the cells belonging to the same functional circuit connect together during development? We use the mouse retina as a model system to address these questions. Finally, we will study the structure and function of a specialised neural circuit in the human fovea that enables humans to read. We predict that our insights into the mechanism of multitasking, network switches and the development of selective connectivity will be instructive to study similar phenomena in other brain circuits. Knowledge of the structure and function of the human fovea will open up new opportunities to correlate human retinal function with human visual behaviour and our genetic technologies to study human foveal function will allow us and others to design better strategies for restoring vision for the blind.

Keywords: retina,neural circuits
Genome Stability Mechanisms in Aging (GENSTAGE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-07-01
End date: 2017-02-28
Duration (months): 68.0
Total project cost (EUR): 1448400.0
EU funding (EUR): 1448400.0
Participants: 2
Project status: CLOSED

Genome Instability has been recognized as causal factor of cancer and recently also as a major contributing factor of aging. A number of progeroid (premature aging-like) syndromes are linked to defects in nucleotide excision repair (NER). NER thus provides a highly relevant experimental system to study the role of genome stability in aging. Using the NER system we recently uncovered a novel link between DNA damage accumulation and the regulation of longevity assurance programs. We propose to use the powerful genetic system of C. elegans to identify mechanisms through which the stochastic accumulation of damage impacts aging and genetic pathways of longevity regulation. We will pursue three complementary experimental strategies: (1) genetic identification of novel response pathways to persistent DNA damage, (2) investigation of DNA damage resistance mechanisms that promote longevity, and (3) a targeted candidate approach to uncover the underlying mechanisms that ensure genome integrity in lifespan extension. This proposal aims at the discovery of novel genes functioning in genome stability and longevity regulation that might be instrumental for the development of preventive therapeutic strategies for age-related pathologies as well as for the treatment of rare genetic progeroid disorders.

Keywords: dna damage,dna repair,ageing,c. elegans genetics,longevity,progeria,hormesis
Global Environmental Decision Analysis (GEDA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: Finland
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2015-12-31
Duration (months): 60.0
Total project cost (EUR): 1495212.8
EU funding (EUR): 1495212.8
Participants: 1
Project status: CLOSED

Habitat degradation and climate change are generally considered the greatest threats to biodiversity globally. Together, these processes pose an urgent challenge to conservation science, requiring ever increasing efficiency in ecologically-based decision making, to slow down, and hopefully eventually reverse, the ongoing global loss of biodiversity. In responding to this challenge, I am proposing a project in which the over-arching goal is to provide improved conservation-oriented analytical methods and tools to underpin knowledge-based land-use planning and associated political decision making. The proposed work builds on a broad established history of research in the field of spatial ecology and conservation prioritization. Specific components of the proposal include: (i) developing the general conceptual, ecological, methodological and statistical basis of environmental and conservation resource allocation: (ii) combining species and community-level prioritization approaches for data-poor areas of the world; (iii) developing methods for alleviating the negative ecological consequences of climate change, based on connectivity both in geographic and environmental space; (iv) developing an uncertainty-analytic method for the planning of habitat restoration and calculation of compensation ratios for habitat that will be impacted due to economic activity, (v) developing methods for allocating alternative conservation actions (protection, maintenance, restoration) in combination with habitat-specific loss rates in spatial conservation prioritization, and (vi) implementing the proposed methods as publicly available, efficient and well-documented software packages. Particular emphasis will be placed on solving the algorithmic challenges involved in analyzing the large data sets that are becoming increasingly available as the distributions of environmental conditions and biodiversity features are derived from large-scale high-resolution remote-sensing data.

Keywords: conservation resource allocation,conservation prioritization,habitat restoration,software
New Algorithms for Host Pathogen Systems Biology (SYSPATHO)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,France,Russian Federation,Türkiye,Cyprus,Israel,Germany
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-10-01
End date: 2015-03-31
Duration (months): 54.0
Total project cost (EUR): 3882716.41
EU funding (EUR): 2942424.75
Participants: 11
Project status: CLOSED

SYSPATHO focuses on the development of novel and generally applicable mathematical methods and algorithms for systems biology. These methods and algorithms will be applied to study the complex interactions of hepatitis C virus (HCV), a human-pathogenic virus of high medical relevance, with its host at the systems level. Using a multidisciplinary, integrative approach, PATHOSYS will (a) develop methods to analyze and integrate a wide variety of data from wet lab experiments, databases and biological literature, (b) develop and apply machine learning tools to reconstruct and study intracellular interaction networks from experimental data, (c) develop new and improve existing algorithms and mathematical methods for bottom-up modelling, to fit models to data, and to analyze the dynamic behaviour of models (d) generate new experimental data to gain novel insights into hepatitis C virus host interactions, and (e) use the newly developed methods and data to model and analyze HCV-host interactions at the systems level. Guided by biological data, PATHOSYS focuses on the design of novel algorithms and mathematical methods for systems biology, with the aim to provide generally applicable tools to elucidate biological processes. Based on developed models and using systems analysis, PATHOSYS will elucidate virus host interactions of Hepatitis C virus at an unprecedented level. As a direct spin-off, models and analysis methods developed in PATHOSYS will lead to the identification of new candidate host cell target genes applicable for the design of novel anti-viral drugs against hepatitis C. Targeting of host cell factors will reduce the likelihood for the development of therapy resistance and increase the chance for broad-spectrum antivirals. Inclusion of two SME partners will ensure exploitation of results generated in PATHOSYS and their transfer into industrial and pharmaceutical applications, thus strengthening economy and health care system in Europe.

Keywords: systems biology,hepatitis c,virus-host interactions,network reconstruction,mathematical modeling,model analysis
Gene Expression Explored in Space and Time Using Single Gene and Single Molecule Analysis (GENEXP)

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: Israel
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2015-11-30
Duration (months): 60.0
Total project cost (EUR): 1498510.0
EU funding (EUR): 1498510.0
Participants: 1
Project status: CLOSED

Live-cell imaging combined with kinetic analyses has provided new biological insights on the gene expression pathway. However, such studies in mammalian cells typically require use of exogenous over-expressed gene constructs, which often form large tandem gene arrays and usually lack the complete endogenous regulatory sequences. It is therefore imperative to design methodology for analyzing gene expression kinetics of single alleles of endogenous genes. While certain steps have been taken in this direction, there are many experimental obstacles standing in the way of a robust genome-wide system for the in vivo examination of endogenous gene expression within the natural nuclear environment. GENEXP sets out to provide such a system. It will start with methodology for robust tagging of a multitude of endogenous genes and their transcribed mRNAs in human cells using the "CD tagging" approach. Thereby, in vivo mRNA synthesis at the nuclear site of RNA birth will be explored in a unique manner. A high-resolution study of gene expression, in particular mRNA transcription and mRNA export, under endogenous cellular context and using a genome-wide live-cell approach will be performed. GENEXP will specifically focus on the: i) Transcriptional kinetics of endogenous genes in single cells and cell populations; ii) Kinetics of mRNA export on the single molecule level; iii) Examination of the protein composition of endogenous mRNPs; iv) High throughput scan for drugs that affect gene expression and mRNA export. Altogether, GENEXP will provide breakthrough capability in kinetically quantifying the gene expression pathway of a large variety of endogenous genes, and the ability to examine the generated molecules on the single-molecule level. This will be done within their normal genomic and biological environment, at the single-allele level.

Keywords: gene expression,mrna dynamics,mrna export,nuclear structure and function,live-cell imaging