Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Complex adaptation in photosynthetic microbes evolving in response to global change. (EVOCHANGE)

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
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-05-01
End date: 2017-04-30
Duration (months): 72.0
Total project cost (EUR): 1492338.0
EU funding (EUR): 1492338.0
Participants: 1
Project status: CLOSED

Microbes evolve rapidly in changing environments, and global change may soon cause future microbial populations to differ genetically and phenotypically from contemporary populations. We have both pragmatic and intellectual interests in microbial evolution, especially when microbial communities perform important ecological services. For example, marine phytoplankton are responsible for half of global primary production, and make up the biological carbon sink in oceans. However, marine environments are changing in complex ways, and future global carbon and energy cycles may depend heavily on how phytoplankton evolve in response to global change. My research will study how photosynthetic microbes evolve in complex environments. First, I will use mathematical models and experimental evolution in a microalgal model system to compare phenotypic changes between populations that have evolved either in an environment where many variables change simultaneously, or in an environment where only one variable changes at a time. Second, I will use the same model system to study if and how heritable epigenetic change, such as methylation and miRNA regulation, affects long-term adaptation. Both sets of experiments will use environmental shifts that are associated with global change, thus providing information specific to marine phytoplankton evolution, as well as insight into fundamental evolutionary processes. Finally, I will use RAD sequening in natural algal isolates from high CO2 environments to map and produce a list of candidate loci that may have contributed to long-term evolution in elevated CO2. The results of this work will significantly improve our ability to use evolutionary theory to understand how microbes are likely to change over the coming decades.

Keywords: microalgae,phytoplankton,fitness landscapes,evolutionary ecology
Towards an individualised therapy and prevention of multi-drug resistant disease (RESISTOME)

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: Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1479487.0
EU funding (EUR): 1479487.0
Participants: 1
Project status: CLOSED

In this proposal the PIs medical microbiology background and previous internationally acknowledged work on molecular persistence mechanism of the gram-negative bacterial pathogen Pseudomonas aeruginosa is exploited towards a novel approach that could change the current paradigm of antibiotic resistance testing. Emerging resistance towards antimicrobials marks this decade and the lack of new therapy options especially against gram-negative pathogens underscores the need for optimisation of current diagnostics, therapies and prevention of the spread of these organisms. The overall objective of this proposal is to apply a multi-disciplinary approach that combines clinical microbiology, state-of-the-art research on molecular resistance mechanisms, next generation-sequencing and array technology to uncover all genetic determinants of antibiotic resistance and to apply research towards the development of innovative molecular diagnostic platforms for rapid detection of resistance in order to accomplish individualised infection control measures, to reduce morbidity and mortality of the patients and to significantly reduce health care costs. The project will be performed at the Helmholtz Centre for Infection Research in Braunschweig which harbors a vast scientific and instrumental infrastructure and is perfectly suited for this type of pioneer research. Molecular diagnostics does not only provide a fast prediction of resistance based on the bacteria´s genotype but when performed directly in patients specimens has promise to transform medical microbiological diagnostics.

Keywords: medical microbiology,multi-drug resistance,genome-wide association studies
PREvention of Late Stent Thrombosis by an Interdisciplinary Global European effort (PRESTIGE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,Italy,Poland,United Kingdom,France,Latvia,Belgium,Germany,Belgium,Spain,Germany,Germany,Netherlands,Germany
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-12-01
End date: 2014-11-30
Duration (months): 48.0
Total project cost (EUR): 7981609.2
EU funding (EUR): 5979641.5
Participants: 15
Project status: CLOSED

According to the European Society of Cardiology there has been an increase in the life expectancy at the age of 65 of the European population from 15.0 to 17.0 years in the years since 1980. In the elderly, up to 50% of deaths are caused by cardiovascular diseases, the majority accounted for by coronary artery disease. The most effective treatment for obstructive coronary disease is percutaneous intervention with coronary stenting and fuelled by the increasing disease burden there has been a rapid increase in the number of percutaneous coronary intervention procedures in Europe from 184,000 in 1992 to 885,000 in 2004. If the rate of progression remains constant, the projected number of coronary intervention procedures per annum will be about 1.5 million by 2010, with a stenting rate of close to 100%. The principal safety issue with current coronary stenting procedures is late stent thrombosis which, with a case mortality rate approaching 50%, makes this problem a very significant European health issue. The PRESTIGE project will result in significant improvement in prediction and prevention of late stent thrombosis by providing novel strategies that causally impede incident events without increasing the overall risk of bleeding. These goals will be achieved by a multidisciplinary consortium formed by world-leading EU-based specialists covering the requisite scientific skills and experience. Since the first drug-eluting stent was introduced in 2002 the growth of this sector has been explosive. Forecasts predicted the potential for this market segment to exceed €4.6 billion by 2009. The economic impact of this very ambitious project will be to provide the European health industries with novel stent products and new imaging technologies to identify patients at-risk, as well as amended European treatment guidelines. The social impact will be, amongst others, a tremendous cost reduction for the public and private health insurance systems all over Europe.

Keywords: stent thrombosis,platelet adhesion,endothelium,coagulation,anti-platelet therapy,imaging
Action Selection under Contextual Uncertainty: the Role of Learning and Effective Connectivity in the Human Brain (ACTSELECTCONTEXT)

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: United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 1341805.0
EU funding (EUR): 1341805.0
Participants: 1
Project status: CLOSED

In a changing world, one hallmark feature of human behaviour is the ability to learn about the statistics of the environment and use this prior information for action selection. Knowing about a forthcoming event allows for adjusting our actions pre-emptively, which can optimize survival. This proposal studies how the human brain learns about the uncertainty in the environment, and how this leads to flexible and efficient action selection. I hypothesise that the accumulation of evidence for future movements through learning reflects a fundamental organisational principle for action control. This explains widely distributed perceptual-, learning-, decision-, and movement-related signals in the human brain. However, little is known about the concerted interplay between brain regions in terms of effective connectivity which is required for flexible behaviour. My proposal seeks to shed light on this unresolved issue. To this end, I will use i) a multi-disciplinary neuroimaging approach, together with model-based analyses and Bayesian model comparison, adapted to human reaching behaviour as occurring in daily life; and ii) two novel approaches for testing effective connectivity: dynamic causal modelling (DCM) and concurrent transcranial magnetic stimulation-functional magnetic resonance imaging. My prediction is that action selection relies on effective connectivity changes, which are a function of the prior information that the brain has to learn about. If true, this will provide novel insight into the human ability to select actions, based on learning about the uncertainty which is inherent in contextual information. This is relevant for understanding action selection during development and ageing, and for pathologies of action such as Parkinson s disease or stroke.

Keywords: action selection,prior information,context,functional neuroimaging,effective connectivity
Functional significance of nociceptive primary sensory neurons diversity (PAINEURONS)

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: France
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-04-01
End date: 2016-03-31
Duration (months): 60.0
Total project cost (EUR): 1457455.0
EU funding (EUR): 1457455.0
Participants: 1
Project status: CLOSED

Unravelling the precise in vivo function of a particular neuronal subpopulation is one of the most challenging issues in neurobiology. Nociceptive primary sensory neurons represent a powerful model system to address this fundamental question. These neurons convey a large cohort of perceptual sensory modalities including thermal, mechanical and chemical stimuli from the periphery to the spinal cord. Nociceptive neurons encompass an extremely heterogeneous population with respect to their morphological, anatomical, electrophysiological and molecular properties. In spite of the efforts, the functional significance of this remarkable diversity has remained elusive. Our proposed project, show our contribution to the expansion of the repertoire of molecules specifying discrete subsets of primary nociceptive neurons and describes original and highly versatile mice models in which the loci of our favourite genes have been genetically engineered to allow conditional gene inactivation and inducible cell ablation of discrete nociceptive neuronal subtypes. Molecular, anatomical, physiological and behavioural analyses of such models will allow to (i) unravel the role of each of our favorite genes in the specification/function of the sensory neuronal subtypes and (ii) correlate discrete subsets of nociceptive neurons to clearly defined sensory modalities. Understanding how diversity in neuronal phenotypes is accomplished is only the first step to deepen into the mechanisms of pain. If we know how a precise neuronal subtype is generated, we can subsequently analyze not only basic aspects of its physiology, but also more medically oriented aspects like its functional role under pathological conditions, its chronic changes in response to inflammation and analgesic treatments

Keywords: genetic engeneering,nociceptive neurons,conditionnal ablation,neuronal subtypes specification
Evolution of flower morphology: the selfing syndrome in Capsella (CAPSEVO)

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,United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2016-11-30
Duration (months): 72.0
Total project cost (EUR): 1480826.0
EU funding (EUR): 1480826.0
Participants: 2
Project status: CLOSED

The change from reproduction by outbreeding to selfing is one of the most frequent evolutionary transitions in plants. This transition is generally accompanied by changes in flower morphology and function, termed the selfing syndrome, including a reduction in flower size and a more closed flower structure. While the loss of self-incompatibility is relatively well understood, little is known about the molecular basis of the associated morphological changes and their evolutionary history. We will address these problems using the species pair Capsella grandiflora (the ancestral outbreeder) and C. rubella (the derived selfing species) as a genetically tractable model. We have established recombinant inbred lines from a cross of C. grandiflora x C. rubella and mapped quantitative trait loci affecting flower size and flower opening. Using this resource, the proposal will address four objectives. (1) We will isolate causal genes underlying the variation in flower size and opening, by combining genetic mapping with next-generation sequencing. (2) We will characterize the developmental and molecular functions of the isolated genes in Capsella and Arabidopsis. (3) We will dissect the molecular basis of the different allelic effects of the causal genes to determine which kinds of mutations have led to the morphological changes. (4) Based on population-genetic analyses of the isolated genes, the evolutionary history of the morphological changes will be retraced. Together, these strands of investigation will provide a detailed understanding of general processes underlying morphological evolution in plants.

Keywords: morphological evolution,capsella,selfing syndrome
Role of obesity in the development of hepatocellular carcinoma (OBECAN)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Spain
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2016-11-30
Duration (months): 72.0
Total project cost (EUR): 1498043.0
EU funding (EUR): 1498043.0
Participants: 1
Project status: CLOSED

Obesity is associated with increased risk for epithelial tumors such as hepatocellular carcinoma (HCC). It is not known, however, whether obesity increases the risk for HCC simply because it promotes cirrhosis, a general risk factor for HCC, or through other mechanisms that operate independently of cirrhosis. Among these, obesity is associated with a chronic inflammatory state, with the release of cytokines such as IL-6 and TNFalpha, well-known HCC mediators. Obesity is normally linked to diabetes and in consequence, to hyperinsulinemia. This increase in circulating insulin levels is suggested to be a factor that contributes to cancer. Moreover, the increase in free fatty acids (FFA) in blood among obese patients promotes a compensatory response from liver that activates the transcription of genes required for beta-oxidation, leading to a reduction in non-physiological stores of lipids in the liver. This increase in beta-oxidation could result in oxidative stress, inflammation and the production of lipid peroxidation bioproducts, which are known mutagens. The precise mechanisms whereby FFA and cytosolic triglycerides exert their effects, resulting in the diabetic phenotype, remain poorly understood. Emerging evidence nonetheless links microRNA (miRNA) with lipid metabolism, suggesting that these small RNAs mediate this increase in beta-oxidation. Our goal is to study how the components of the obesity state (inflammation, steatosis hyperinsulinemia and microRNA control of gene regulation) affect HCC development. We will use several mouse models in which one or more of these factors are reduced following induction of metabolic disease. We will also determine whether specific miRNAs that are down- or upregulated in the liver of mice on a high fat diet are implicated in HCC development.

Keywords: obesity,microrna,inflammation,insulin,esteatosis
Understanding genetic control of global gene expression in human macrophages to discover new immune mechanisms protecting from tuberculosis. (TB-IMMUNOGEN)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: ERC Starting Grant Interdisciplinary Panel
Countries involved: United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2015-12-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Tuberculosis (TB) is a major global problem that urgently requires new preventive and therapeutic approaches. Only minority of people infected with M. tuberculosis develops active TB. Genetic studies provide an unbiased way to scan the whole human genome to find sequence polymorphisms that predispose to TB. Therefore, we have established the world s largest sample collection for TB genetic studies. Now we genotype 6,000 HIV-negative patients with pulmonary TB and 6,000 healthy controls at ~1 million polymorphic sites across the whole genome. This genome-wide association study (GWAS) will allow us to compare frequency of genetic variants among patients and controls to find genes that protect from TB. Given that susceptibility to TB is a complex disease, a complementary strategy in genetic research is to identify variants that control intermediate cellular phenotypes. Here, for the first time I will undertake a large-scale study to identify polymorphisms that control gene expression in human macrophages, cells that play key role in protection from M. tuberculosis. We will study in vitro global gene expression in uninfected and M. tuberculosis-infected macrophages from hundreds of healthy volunteers correlating it with the genome-wide genotype data of these subjects. This will allow us to identify variants that regulate differential gene expression in macrophages upon M. tuberculosis infection. We will also study functional effects of the polymorphisms associated with TB risk in the previous and ongoing studies. Taken together these experiments will discover genes and biological pathways involved in protection from M. tuberculosis and will characterise macrophage transcription profile of subjects that are genetically predisposed to TB.

Keywords: tuberculosis
Integrating the Multiple Meta-Analysis: a framework for evaluating and ranking multiple health care technologies. (IMMA)

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: Greece
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-10-01
End date: 2015-12-31
Duration (months): 63.0
Total project cost (EUR): 592500.0
EU funding (EUR): 592500.0
Participants: 1
Project status: CLOSED

Health care practitioners face daily questions and make choices regarding the effectiveness and quality of several health technologies (e.g. alternative interventions). On this regard they usually consider meta-analysis; the statistical synthesis of results from relevant experiments. The main drawback of the current state of the art is that meta-analysis focuses on comparing only two alternatives. However, clinicians and scientists need to know the relative ranking of a set of alternative options and not only whether option A is better than B. There is an urgent need to establish and disseminate a robust framework for selecting among many treatment options, possibly after taking into account environmental and genetic interactions. The goal of the proposed project is to provide this by establishing and disseminating a revolutionary evidence synthesis toolkit. Its main methodological vehicle is a flexible statistical framework using Bayesian techniques for multiple-treatments meta-analysis. This will enable the relative ranking of all alternative health care options, will allow comprehensive use of all available data, will improve precision and confidence in the conclusions and will answer methodological questions related to bias. Once established in clinical epidemiology, the tool will be extended to genetic epidemiology to account for multiple genetic markers, environmental factors and effects of treatments. Based on ongoing collaborations with teams undertaking applied health care research I plan to evaluate the new tool empirically in real-life health care problems such as ranking the pharmacological treatments for osteoarthritis, indicating the best treatments for multiple sclerosis and ranking the vaccines for influenza.

Keywords: meta-analysis,statistical modelling,guidelines
Amino acid sensing by TOR (TOR-AA)

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: 2010-09-01
End date: 2015-08-31
Duration (months): 60.0
Total project cost (EUR): 1499279.2
EU funding (EUR): 1499279.2
Participants: 1
Project status: CLOSED

The kinase TOR is a key regulator of cell growth and organismal metabolism in animals. Consequently, the correct regulation of TOR activity is important both for normal development and for disease. For instance, TOR is hyperactivated in almost all human cancers, and reduced TOR activity is associated with leanness and resistance to obesity. TOR activity is regulated by a number of inputs including, importantly, amino acids. Indeed, nutritional amino-acid overload in humans is thought to promote insulin resistance via TOR activation. However, the molecular mechanism by which amino acids regulate TOR is still mysterious. I propose here to identify and characterize factors required for amino acids to regulate TOR. We will use a genome-wide functional-genomics approach to systematically identify a large number of genes involved in this process, thereby hopefully making a significant contribution to the field. Identification of these novel factors may open avenues for diagnosis and treatment of cancer and metabolic disease. This project will exploit a high-throughput, cell-based screen for genes involved specifically in amino acid sensing by TOR which we have implemented in my lab. In collaboration with the neighboring Boutros lab, we have performed a pilot screen on the 780 kinases of the human genome, proving that the screen is working successfully, and yielding a number of interesting hits which we have validated. The PhD student in my lab who performed the pilot screen is now characterizing these new genes. I would like to fully exploit this platform by executing the screen on a genome-wide level, and following-up on the genes that will be discovered. However, I do not have the necessary resources to do so. An ERC starting grant would allow us to do this, leveraging our technology platform and the work we invested in creating it. I strongly believe these results will be exciting and of general interest, helping to establish me in the field.

Keywords: drosophila