Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Nitrification Reloaded - a Single Cell Approach (NITRICARE)

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: Austria
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-05-01
End date: 2017-04-30
Duration (months): 60.0
Total project cost (EUR): 2499107.0
EU funding (EUR): 2499107.0
Participants: 1
Project status: CLOSED

Nitrification is a central component of the Earth’s biogeochemical nitrogen cycle. This process is driven by two groups of microorganisms, which oxidize ammonia via nitrite to nitrate. Their activities are of major ecological and economic importance and affect global warming, agriculture, wastewater treatment, and eutrophication. Despite the importance of nitrification for the health of our planet, there are surprisingly large gaps in our fundamental understanding of the microbiology of this process. Nitrifiers are difficult to isolate and thus most of our current knowledge stems from a few cultured model organisms that are hardly representative of the microbes driving nitrification in the environment. The overarching objective of NITRICARE is to close some of these knowledge gaps and obtain a comprehensive basic understanding of the identity, evolution, metabolism and ecological importance of those bacteria and archaea that actually catalyze nitrification in nature. For this purpose innovative single cell technologies like Raman-microspectroscopy, NanoSIMS and single cell genomics will be combined in novel ways and a Raman microfluidic device for high-throughput cell sorting will be developed. Application of these approaches will reveal the evolutionary history and metabolic versatility of uncultured ammonia oxidizing archaea and will provide important insights into their population structure. Furthermore, the proposed experiments will allow us to efficiently search for unknown nitrifiers, evaluate their ecological importance and test the hypothesis that organisms catalyzing both steps of nitrification may exist. For non-model nitrifiers we will develop a unique genetic approach to reveal the genetic basis of key metabolic features. Together, the genomic, metabolic, ecophysiological and genetic data will provide unprecedented insights into the biology of nitrifying microbes and open new conceptual horizons for the study of microbes in their natural environments.

Keywords: single cell microbiology,nitrification,molecular ecology,microbial physiology
p53 control of epithelial homeostasis (PICHO)

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: Israel
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-10-01
End date: 2017-09-30
Duration (months): 60.0
Total project cost (EUR): 2499999.6
EU funding (EUR): 2499999.6
Participants: 1
Project status: CLOSED

Background: Our recent studies implicate p53 in gut tissue homeostasis - suppressing epithelial invasion. This function is tightly linked to suppression of a gene cluster (PSIS- p53-Suppressed Invasiveness Signature), which requires Wnt activation and other cues, yet is only expressed upon loss of p53. The invasive signature explains a broad spectrum of the invasiveness property, from the loss of enterocyte polarity to matrix degradation, pointing to a concerted action. We documented a tight association between invasiveness and coexpression of several PSIS genes in different mouse models and showed that PSIS expression is essential in mediating epithelial cell invasiveness following p53 depletion. Goal: Elucidate functions of p53 activation which are of particular importance for epithelial tissues. Understand how WT p53 contributes to preserving epithelial boundaries, prohibiting invasion and abnormal cell mixture and controlling stem cell dynamics under tissue stress. Methodology: We will investigate the epithelial role of p53 and the invasive signature genes in several mouse models of inflammatory bowel diseases and intestinal cancer. These models will incorporate p53-modulating switchable genetic elements and cell-tracking genetic markers for monitoring tissue dynamics. Analyses of relevant human pathology samples will complement the mouse studies. Significance: Invasion is a defining hallmark of malignancy and understanding early invasion of tumor cells is of fundamental importance in designing future therapies for cancer - targeting PSIS is an example. PSIS database may also be used to develop biomarkers for distinguishing malignant tumors from benign ones, a critical determinant of therapeutic options in several types of cancers, currently solely based on morphologic assessment. A molecular definition of early invasive lesions may allow early implementation of curative treatments while withholding patient overtreatment which often results in serious morbidity.

Keywords: epithelial cancer,inflammatory bowel disease,p53,tumor suppressor,wnt activation,tissue boundaries,invasion,tissue stem cell dynamics.
Morphodynamics in Plants: from gene to shape (MORPHODYNAMICS)

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: France
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-05-01
End date: 2018-04-30
Duration (months): 72.0
Total project cost (EUR): 2368004.0
EU funding (EUR): 2368004.0
Participants: 1
Project status: CLOSED

Morphodynamics is aimed at understanding how shape in plants is controlled during development, a major issue in developmental biology.. So far, research in the field has been mainly based on qualitative observations of mutants, with little considerations for the physics of the cells and tissues leaving many questions unanswered or unexplored. Here, using recent technological advances, to which the applicant has largely contributed, we propose an interdisciplinary and quantitative analysis of molecular and biophysical growth parameters from the cell to the organ level. Because the mechanical properties of the cell wall are generally accepted to control local growth rates and directions, their contribution to morphogenesis will be the central focus. How the molecular regulatory networks, including cell identity genes, influence cell wall synthesis and structure to induce local growth rates and directions is largely unknown at present, mainly because our knowledge lacks integration at different levels of complexity. In addition to the quantitative and interdisciplinary character of this proposal, an original aspect of the project will address the multi-scale nature of a growing tissue, establishing a causality link between local wall properties and multi-cellular outputs. To address this issue, we will combine cutting edge live imaging tools and micromechanical approaches with modelling frameworks recently developed in our laboratory. This will be performed using the developing flower in Arabidopsis, one of the best studied systems in biology and which has the strong advantage to grow without cell migration or rearrangement, vastly facilitating the dialog between the observations and the predictions from the models. In summary, using different interdisciplinary concepts and methods, developed in our laboratory and coming from biology, physics and computer science, we will produce for the first time a mechanistic and multi-scale view of the growing flower bud.

Keywords: flower,growth,cell wall
Molecular and cellular imaging of membrane interactions in pathogen attack and immune defense (MEMBRANEATTACK)

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-2011-ADG_20110310, 2011)
Start date: 2012-06-01
End date: 2018-05-31
Duration (months): 72.0
Total project cost (EUR): 2311036.0
EU funding (EUR): 2311036.0
Participants: 1
Project status: CLOSED

The immune system and pathogens both use membrane pore-forming proteins to penetrate cellular membranes, in order to kill target cells or to allow passage of pathogenic organisms such as malaria parasites, listeria, or toxoplasma. For both fundamental and practical reasons, it is important to understand the biological actions of the "arms race" underlying virulence, pathogenesis and immune defense. The key weapon in this membrane attack is a class of proteins that upon activation undergo a dramatic conversion from water-soluble monomers to a large, membrane-inserted assembly. Both the human immune response and microbial pathogenesis rely on membrane disruption by perforin-like proteins for attack and counterattack. This protein superfamily encompasses perforin and complement pore-forming assemblies in the immune system, as well as the more distantly related bacterial cholesterol-dependent cytolysins. With recent advances in electron cryo-microscopy, tomography and correlative fluorescence microscopy, it is now possible to relate the workings of protein machines in model systems such as liposomes to their actions in the cellular context. I wish to capitalize on these technical advances and visualize membrane interactions at the moment the intracellular pathogen Toxoplasma gondii bursts out of its host cell, as well as the delivery of lethal cargo from the cytotoxic lymphocyte to its target cell through the immune synapse. These studies will correlate 3D spatial information at cellular and molecular levels to reveal the operation of dynamic cellular machinery. I have chosen a well-ordered system that can bridge the gulf between cell biology and atomic structure. Innovations in sample preparation combined with state-of the art imaging methods will lead to the molecular definition of a fundamental process in “hostile” communication between cells and will broaden the landscape for drug design for immune disorders and major infectious diseases.

Keywords: membrane pore-forming proteins immune synapse parasite egress
Bacterial Persistence (PERSIST)

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: Denmark,United Kingdom
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-05-01
End date: 2017-04-30
Duration (months): 60.0
Total project cost (EUR): 2455110.0
EU funding (EUR): 2455110.0
Participants: 2
Project status: CLOSED

Almost all bacterial species generate persisters, individual cells that are tolerant to antibiotics. Persisters have entered a dormant or slow growing state in which they are recalcitrant to the killing activity of most known antibiotics. The molecular mechanisms underlying bacterial persistence are unknown and there is a pressing need to develop new methods and approaches to study the phenomenon. We discovered recently that RNA endonucleases (RNases) encoded by toxin - antitoxin (TA) genes are required for persistence of the model bacterium Escherichia coli. We have shown that the RNases inhibit translation by cleavage of mRNA or tRNA and that their activation halts cell growth and induces persistence. We propose a testable model in which persistence is induced by stochastic activation of the RNases. Almost all free-living bacteria, including many serious pathogens, have TA genes, often in multiple or even many copies. For example, the major pathogen Mycobacterium tuberculosis, which can persist in the human body for many years, has at least 88 TA loci. This proposal describes a research program dedicated to develop novel general methods to study the persistence phenomenon and to test the hypothesis that TA loci are central to bacterial persistence. The implementation of novel, leading edge technologies will allow a profound understanding of the persistence phenomenon. Mechanistic insight into the persistence problem, in turn, will provide a basis for a rational approach to the development of drugs and drug administration regimes that may improve treatment of persistent infections.

Keywords: persistence,bacteria,translation,mrna & trna degradation,mrnase,toxin,antitoxin,lon protease,rele,relb,growth inhibition,antibiotic,tolerance,infection,e. coli,salmonella,p. aeruginosa
Reporter models for the Evaluation of Diseases involving OXidative stress (REDOX)

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: United Kingdom
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-03-01
End date: 2017-02-28
Duration (months): 60.0
Total project cost (EUR): 2486524.0
EU funding (EUR): 2486524.0
Participants: 1
Project status: CLOSED

Perturbations in cellular redox status are implicated in many human diseases, yet there is an extreme lack of knowledge about the effects of oxidative stress in vivo, mainly due to difficulties in measuring reactive oxygen species (ROS) in vivo and the absence of experimental models. REDOX will use novel transgenic technologies to develop mouse models that report on ROS in vivo, allowing spatio-temporal monitoring of different types of oxidative stress, ultimately simultaneously in a complex reporter line, and clarifying its role in the aetiology of disease and pathways of drug & chemical toxicity. These models will reveal oxidative stress as a primary cause, or a consequence, of the disease process. Reporters will be driven by endogenous genes regulated by different forms of oxidative stress and, uniquely, we will exploit the sophisticated redox sensing systems in bacteria to discern different types of ROS. In a sophisticated system we will express 3 reporters from the same stress regulated promotor, generating a polycistronic mRNA by use of the FMDV 2A sequence, which cleaves the nascent polypeptide to yield the endogenous gene product and individual reporters. LacZ will be used as an in situ reporter, luciferase for imaging, and a secreted protein, eg hCG, as a non-invasive biomarker in blood or urine. The in vivo role of oxidative stress in disease aetiology, and the potential of novel anti-oxidants to prevent such diseases, will be evaluated in these models. A further novel aspect will be to generate ES cells from the reporter lines, and create genetically-driven disease models which reflect inherited human diseases. REDOX combines ambitious experimental systems with sophisticated novel technologies to create models to define the role of oxidative stress in human disease, offering a new approach in defining and testing of disease prevention and therapeutic interventions while reducing the number of animals required.

Keywords: oxidative stress,transgenic models
High-throughput dissection of the genetics underlying complex traits (COMPLEX_TRAITS)

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: Germany
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-11-01
End date: 2017-10-31
Duration (months): 60.0
Total project cost (EUR): 2499821.0
EU funding (EUR): 2499821.0
Participants: 1
Project status: CLOSED

The vast majority of genetic diseases are complex traits, conditioned by multiple genetic and environmental factors. Yet our understanding of the genetics underlying such traits in humans remains extremely limited, due largely to the statistical complexity of inferring the effects of allelic variants in a genetically diverse population. Novel tools for the dissection of the genetic architecture of complex traits, therefore, can be most effectively developed in model organisms, where the contribution of individual alleles can be quantitatively determined in controlled genetic backgrounds. We have previously established the yeast Saccharomyces cerevisiae as a model for complex traits by unravelling complex genetic architectures that govern quantitative phenotypes in this organism. We achieved this by pioneering approaches that have revealed crucial information about the complexity of the underlying genetics. Here we propose to advance to the next level of complex trait dissection by developing systematic, genome-wide technologies that aim to identify all of the variants underlying a complex trait in a single step. In particular, we will investigate traits involved in mitochondrial function, which are both clinically relevant and highly conserved in yeast. Our combination of genomic technologies will allow us to: 1) systematically detect, with maximal sensitivity, the majority of genetic variants (coding and non-coding) that condition these traits; 2) quantify the contributions of these variants and their interactions; and 3) evaluate the strengths and limitations of current methods for dissecting complex traits. Taken together, our research will yield fundamental insights into the genetic complexity of multifactorial traits, providing valuable lessons and establishing novel genomic tools that will facilitate the investigation of complex diseases.

Keywords: complex trait,genetic variant,quantitative phenotype,qtl,bulk segregant analysis,linkage mapping,high-throughput,genome-wide,reciprocal hemizygosity analysis,yeast,mitochondria
Dissecting genotype-phenotype relationships using high-throughput genomics and carefully selected study populations (BATESON)

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: Sweden
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-05-01
End date: 2017-04-30
Duration (months): 60.0
Total project cost (EUR): 2300000.0
EU funding (EUR): 2300000.0
Participants: 1
Project status: CLOSED

A major aim in genome research is to reveal how genetic variation affects phenotypic variation. Here I propose to use high-throughput genomics (whole genome sequencing, transcriptome and epigenome analysis) to screen carefully selected study populations where the chances are particularly favourable to obtain novel insight into genotype-phenotype relationships. The ambition is to take discoveries all the way from phenotypic characterization to the identification of the genes and the actual genetic variant causing a phenotypic effect and to understanding the underlying functional mechanisms. The program will involve a fish (the Atlantic herring), a bird (the domestic chicken) and a mammal (the European rabbit). The Atlantic herring will be studied because it provides unique opportunities to study the genetics of adaptation in a natural population and because of the possibilities to revolutionize the fishery management of this economically important marine fish. We will generate a draft assembly of the herring genome and then perform whole genome resequencing of different populations to reveal the population structure and the loci underlying genetic adaptation. The European rabbit is an excellent model for studying the genetics of speciation due to the presence of two distinct subspecies on the Iberian Peninsula. The domestication of the rabbit is also particularly interesting because it is a recent event (about 1500 years ago) and it is well established that domestication happened from the wild rabbit population in southern France. Finally, the domestic chicken provides excellent opportunities for in depth functional studies since it is both a domestic animal harbouring a rich genetic diversity and an experimental organism. (BATESON is the acronym for this proposal because Bateson (1902) pioneered the study of genotype-phenotype relationships in animals and used the chicken for this work.)

Keywords: evolution fisheries speciation bioinformatics
New and more individualised population-based screening for cardiovascular disease; from a RCT including selfassessments, primary care and coronary artery calcification score to modelling risk-benefit (ROBINSCA)

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: Netherlands,Netherlands
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-12-01
End date: 2018-11-30
Duration (months): 72.0
Total project cost (EUR): 3298999.0
EU funding (EUR): 3298999.0
Participants: 2
Project status: CLOSED

Cardiovascular disease currently is the primary cause of death of two million people in Europe each year. Early cardiovascular disease can be treated effectively and at ever-lower costs. This has raised hopes that if large groups of individuals who are at an increased risk could be identified earlier, morbidity and mortality from the disease could potentially be reduced. New risk questionnaires, biomarkers and computed tomography imaging technology (CT) have identified undiagnosed increased risks in asymptomatic people. However, it is unknown whether such screening for subclinical disease improves outcomes enough to justify the associated adverse effects and costs of the new strategies. Benefits are only to be expected if large groups of asymptomatic people can be reached. Moreover, evidence can only be shown unambiguously in randomised controlled trials (RCTs). We therefore propose a large-scale population-based screening trial, in which we will invite 330,800 men and women (from population-based registries) to measure their waist circumference and fill out a risk questionnaire. 39,000 persons at elevated risk will then be randomised to either: a) no testing, b) be screened using the classic tests (lipids, glucose, blood pressure) or c) be screened using a CT scan of the coronary arteries. The first objective of the trial is to establish whether inviting (and subsequently selecting high-risk) asymptomatic men and women for a ‘classic’ risk factor assessment, followed by early and intensive medical intervention in subjects at increased risk, will decrease coronary heart disease (CHD) mortality and morbidity by 15% or more within five years. The second objective is to establish whether the coronary calcium score using CT will improve outcomes with another 15% for asymptomatic persons. The third objective is to model the natural history of atherosclerotic plaques and CHD risk, to estimate effects, adverse effects and costs, and to guide public health policies.

Keywords: screening evaluation,rct,waist circumference,blood tests,coronary artery calcium score,harms and benefits,modelling natural history,population-based