Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
NMD Complexes: Eukaryotic mRNA Quality Control (COMPLEXNMD)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2016-11-30
Duration (months): 58.0
Total project cost (EUR): 1176825.0
EU funding (EUR): 1176825.0
Participants: 1
Project status: CLOSED

Nonsense-mediated mRNA decay (NMD) is an essential mechanism controlling translation in the eukaryotic cell. NMD ascertains accurate expression of the genetic information by quality controlling messenger RNA (mRNA). During translation, NMD factors recognize and target to degradation aberrant mRNAs that have a premature stop codon (PTC) and that would otherwise lead to the production of truncated proteins which could be harmful for the cell. A wide range of genetic diseases have their origin in the mechanisms of NMD. Discrimination of a PTC from a correct termination codon depends on splicing and translation, and it is the first and foremost step in human NMD. The molecular mechanism of this process remains elusive to date. In the research proposed, I will undertake to elucidate the molecular basis of translation termination and induction of NMD. I will study complexes involved in human translation termination at a normal stop codon and involved in NMD. I will employ an array of innovative techniques including recombinant production of human protein complexes by the MultiBac system, mammalian in vitro translation, mass spectrometry for detecting relevant protein modifications, biophysical techniques, mutational analyses and RNA-interference experiments. Stable ribosomal complexes with termination factors and complexes of NMD factors will be used for structure determination by cryo-electron microscopy. State-of-the-art image processing will be applied to address the inherent heterogeneity of the complexes. Hybrid approaches will allow the combination of cryo-EM structures with existing high-resolution structures of factors involved for generation of quasi-atomic models thereby visualizing molecular mechanisms of NMD action. This interdisciplinary work will foster our understanding at a molecular level of a paramount step in mRNA quality control, which is a vital prerequisite for the development of new treatment strategies in NMD-related diseases.

Keywords: nonsense-mediated mrna decay,cryo-electron microscopy,translation termination,multiprotein complexes,in vitro translation
Toward Eco-Evolutionary Models for BIODiversity Scenarios (TEEMBIO)

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: France
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1482705.0
EU funding (EUR): 1482705.0
Participants: 1
Project status: CLOSED

Given the contemporary biodiversity crisis, effective conservation strategies that offset the threats to ecosystem integrity are crucial for maintaining biodiversity. The development of sound biodiversity scenarios is thus a major challenge for the scientific community. However, current biodiversity models rarely incorporate recent advances in ecological and evolutionary theory like: (i) how evolution shapes species’ niches and ranges; (ii) how community assembly rules shape species' ranges; and (iii) how these two processes interact to drive the response of populations and communities to environmental changes. Since the considered processes act on the opposing ends of an organisational hierarchy, they have rarely been combined and no model integrating all these processes yet exists. The task of bridging the gap between local processes and macroecological species range dynamics is to build upon theoretical and empirical approaches from evolutionary ecology and community ecology, to extract the processes relevant for higher-scale dynamics and to account for their interactions to generate biodiversity scenarios and associated services. The key-idea of the proposed project TEEMBIO is thus to fill this gap through four interrelated research axes: 1- Improve our understanding on how evolution shapes species ranges at micro- and macro-evolutionary scales. 2- Improve our understanding on how community assembly rules shape biodiversity and species. 3- Develop, analyze and parameterize comprehensive projection tools (EEM-models) that incorporate both evolutionary dynamics and community assembly rules to predict global change impacts on biodiversity. 4- Develop a set of quantitative scenarios of plant biodiversity and associated ecosystem services using two case studies (forest in European Alps and grasslands in French Alps) with a comprehensive assessment of protected area networks

Keywords: biodiversity scenarios community ecology species distribution models rapid adaptation niche evolution novel models
Optical dissection of circuits underlying fast cholinergic signalling during cognitive behaviour (BRAINSIGNALS)

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: Netherlands
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1499242.0
EU funding (EUR): 1499242.0
Participants: 2
Project status: CLOSED

Our ability to think, to memorize and focus our thoughts depends on acetylcholine signaling in the brain. The loss of cholinergic signalling in for instance Alzheimer’s disease strongly compromises these cognitive abilities. The traditional view on the role of cholinergic input to the neocortex is that slowly changing levels of extracellular acetylcholine (ACh) mediate different arousal states. This view has been challenged by recent studies demonstrating that rapid phasic changes in ACh levels at the scale of seconds are correlated with focus of attention, suggesting that these signals may mediate defined cognitive operations. Despite a wealth of anatomical data on the organization of the cholinergic system, very little understanding exists on its functional organization. How the relatively sparse input of cholinergic transmission in the prefrontal cortex elicits such a profound and specific control over attention is unknown. The main objective of this proposal is to develop a causal understanding of how cellular mechanisms of fast acetylcholine signalling are orchestrated during cognitive behaviour. In a series of studies, I have identified several synaptic and cellular mechanisms by which the cholinergic system can alter neuronal circuitry function, both in cortical and subcortical areas. I have used a combination of behavioral, physiological and genetic methods in which I manipulated cholinergic receptor functionality in prefrontal cortex in a subunit specific manner and found that ACh receptors in the prefrontal cortex control attention performance. Recent advances in optogenetic and electrochemical methods now allow to rapidly manipulate and measure acetylcholine levels in freely moving, behaving animals. Using these techniques, I aim to uncover which cholinergic neurons are involved in fast cholinergic signaling during cognition and uncover the underlying neuronal mechanisms that alter prefrontal cortical network function.

Keywords: acetylcholine attenion behaviour prefrontal cortex nucleus basalis
Regulation of Polycomb Complex (PRC2) during development and in diseases (REPODDID)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Genetics,Genomics,Bioinformatics and Systems Biology
Countries involved: France
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1499815.2
EU funding (EUR): 1499815.2
Participants: 1
Project status: CLOSED

Polycomb Group (PcG) proteins are pivotal for the specification and maintenance of cell identity by preventing inappropriate gene activation. They function mostly through the regulation of chromatin structure and, in particular, the post-translational modification of histones. Although the enzymatic activities of the main PcG complexes has been described, lots remain to be discovered in terms of how these chromatin modifying activities are regulated. Genome wide analysis uncovered genes that are targeted by PcG proteins in various model cell lines, however it still very unclear how PcG proteins are targeted to a specific set of genes depending on the cell type. Finally, PcG proteins are frequently fund deregulated in diseases among which cancer but whether the alteration of their expression is a causative event to pathologies requires further investigation. This proposal is focused on the Polycomb Repressive Complex 2 (PRC2) whose function is pivotal to the polycomb machinery. In the first two aims of this proposal, we will investigate mechanistically how transcription factors, non-coding RNAs and chromatin structure might independently or in conjunction establish the conditions conducive to gene targeting by PRC2 and regulate its activity. In the third and fourth aims of this proposal, we will investigate what is the function of PRC2 during tumorigenesis and cell reprogramming and how its function is regulated during these processes.

Keywords: chromatin,polycomb,prostate cancer,histone variant,non-coding rna
Human leukemic stem cells: from identification towards targeting and eradication (HULSCTARGETING)

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: Netherlands
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1499820.0
EU funding (EUR): 1499820.0
Participants: 1
Project status: CLOSED

Human myeloid leukemias are life-threatening disorders. Although with current therapies the bulk of the tumor is readily eradicated, it is particularly the rare population of leukemic stem cells (LSCs) that is relatively quiescent and is very difficult to target. As a consequence, relapse of the disease occurs frequently resulting in poor survival rates. Nevertheless, remarkable differences do exist between subsets of patients. It is important to realize that leukemias are rather heterogeneous disorders that can be caused by a multiplicity of genetic and epigenetic changes. One of the most important challenges in the field today lies in establishing which of the differences between LSCs and normal hematopoietic stem cells (HSCs) provide attractive targets for the identification, targeting and ultimately the selective eradication of LSCs. Given the heterogeneity of the disorder, it will be important to address these aspects in detail in a leukemia subtype-specific manner. Central to this proposal is the establishment of a human xenograft mouse leukemia “clinic” in which all important human leukemia subtypes will be represented. LSCs from patients as well as from cord blood and bone marrow model systems that we have generated will be equipped with luciferase-GFP tracers in order to allow detection of leukemic development in alive immunodeficient mice, as well as with unique barcodes that will allow clonal tracking. Within this mouse clinic, in a leukemia subtype-specific manner, we will be able to: 1) identify (novel) leukemic stem cell markers and evaluate their targetability; 2) evaluate whether stem cell intrinsic versus extrinsic signaling can be used as targets in alternative approaches to eradicate LSCs, and 3) study clonal evolution from de novo to relapsed leukemia. Our studies should provide insight into the biology of leukemia and novel rational approaches to treat leukemia patients more successfully.

Keywords: leukemia,human leukemic stem cells,tumor stem cell targeting
Tolerance Restoration In Autoimmune Diseases by selective manipulation of the CD28 costimulatory pathway (TRIAD)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: France,Netherlands,United Kingdom,France,Brazil,United Kingdom
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2012-01-01
End date: 2014-12-31
Duration (months): 36.0
Total project cost (EUR): 4083712.36
EU funding (EUR): 2959590.0
Participants: 7
Project status: CLOSED

The TRIAD, Tolerance Restoration In Autoimmune Disease, consortium provides an innovative strategy to autoimmune diseases (AID) therapy, based on antibody approach with a well established mechanism of action. The main objective is the evaluation of a selective antagonist of CD28 to prevent, treat and/or cure some AIDs in preclinical models including rheumatoid arthritis, multiple sclerosis, type 1 diabetes, psoriasis, uveitis and arteriosclerosis. The concept is based on rather than suppressing the immune system as a whole, suppressing only the parts of the immune system responsible for the autoimmune attack, while sparing and enhancing regulatory T cells. Costimulation through the CD28/B7/CTLA-4 molecular triad controls the balance effector/regulatory functions after initial antigen exposure. An antagonist anti-CD28 represents a novel drug candidate allowing very specific immunosuppression compatible with regulatory T cells function, immune regulation and therefore tolerance induction/restoration. The TRIAD project will start with the study of the efficacy of a new selective antagonist of CD28 in non-human primate models and the exploration of the potential efficacy of surrogate CD28 antagonist in rodent models. Then will be performed an evaluation of potential immunological toxicity of the antagonist in humanized SCID mice and non-human primate, to exclude agonist activity in vivo. Previously identified mechanisms of action (i.e. costimulation blockade and induction of Tregs) in the context of AID will be confirmed in experimental models. Formulation and preclinical toxicological studies will be run before initiating PhaseI/II trial in patients. TRIAD capitalises on the strong experience available in Brazil and Europe in the field of immunology. It comprises 6 academic institutions and 1 SME being the coordinator of the 3-year project. International cooperation with project is ensured by the integration of a leading Brazilian research centre in the consortium.

Keywords: costimulation,cd28,ctla-4,regulatory t lymphocyte,preclinical development,autoimmune disease
Linking Pathogen Evolution and Epidemiology (PATHEVOL)

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-2011-StG_20101109, 2011)
Start date: 2011-10-01
End date: 2016-09-30
Duration (months): 60.0
Total project cost (EUR): 1498811.0
EU funding (EUR): 1498811.0
Participants: 1
Project status: CLOSED

The goal of the proposed research is a comprehensive understanding of how evolutionary potential of pathogen populations interacts with epidemiological dynamics in natural populations. The empirical work will be conducted on the specialist fungal pathogen Podosphaera plantaginis and its host plant Plantago lanceolata in a large network of host populations. I will address the key theories of pathogen evolution, involving life-history trade-offs, competition for resources under multiple infection, and sexual reproduction. This project takes advantage of the exceptional research opportunities offered by the focal study species to test models that have not been validated with respect to realized population dynamics and the persistence of pathogen populations. I have studied the coevolutionary dynamics between P. plantaginis and P. lanceolata for several years. Unique epidemiological data have been collected annually on the occurrence of the pathogen in a network of 4000 host populations since 2001. Recently, I have generated an EST library for the pathogen that allows and facilitates genetic studies. In the planned research, I will combine laboratory experiments with large-scale population surveys, genetic studies and mathematical modelling to achieve the objectives of this proposal. The proposed research has potential for groundbreaking results on pathogen evolution and epidemiology through: i) Simultaneous study of multiple forces driving pathogen evolution and their importance in natural populations, with direct connections to epidemiology. ii) Development of new methodology for the study of obligate parasites like P. plantaginis. iii) Construction of a stochastic, spatially explicit epidemiological model predicting pathogen occurrence from one season to the next with applicability to a wide range of pathogens. iv) Identifying critical life-history stages and mechanisms for virulence evolution yield much needed insights and tools into the battle against disease.

Keywords: epidemiology,coevolution,metapopulation dynamics,red queen,virulence evolution
REsearch into POlicy to enhance Physical Activity (REPOPA)

Framework: FP7 — Cooperation
Programme: Health
Destination: Optimising the delivery of healthcare to European citizens
Action type: Collaborative project
Countries involved: Denmark,Netherlands,Finland,Romania,Italy,Canada,Denmark,Netherlands,United Kingdom
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2016-09-30
Duration (months): 60.0
Total project cost (EUR): 3799411.83
EU funding (EUR): 2996462.0
Participants: 10
Project status: CLOSED

In line with the Call’s overall objective, the basic concept of the proposal is to integrate scientific research knowledge (=evidence), expert know-how and the real world policy making processes to increase synergy and sustainability in promoting health and preventing disease among Europeans. The REsearch into POlicy in Physical Activity (REPOPA) consortium will take up this challenge and will bring together scientific researchers from different disciplines and expertise, policy makers as well as stakeholders, including citizens, whom the policies concern. The five project years will be used to build on evidence and experiences, study innovative ‘win-win’ ways to collaborate between academia and policy makers, and establish structures and best practices for future European health promotion. The objectives are: 1) to assess needs, role and use of research evidence in policy making (WP1); 2) to study ways research evidence is combined and negotiated with ‘other kind of evidence’ in cross-sector policy making process with the focus on physical activity policies (WP1, WP2, WP3); 3) via two interventions to explore innovative ways to translate research evidence into policy making process (WP2 & WP3); 4) to further translate the results into guidance and tools for the future enhancement of evidence-informed policy making in Europe (WP4); 5) to disseminate the results and lessons learned widely and to build structures to enhance sustainability in evidence-informed policy making (WP6); and 6) to evaluate the results and processes as well as impact of the REPOPA (WP5). REPOPA consortium brings in scientific excellence in health research, including physical activity and links it with real life experience in policy making and expertise in knowledge translation from different regions and in six countries in Europe and in Canada. Overall, REPOPA is in line with the concept of Health in All Policies.

Keywords: research evidence,policy making,physical activity,health promotion
Defining the Impact of Chromosome Instability in Tumor Initiation, Maintenance and Relapse (MADCIN)

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: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2018-01-31
Duration (months): 72.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 2
Project status: CLOSED

Chromosomal instability (CIN), the inability to correctly segregate sister chromatids during mitosis, is a hallmark of cancer cells. Overexpression of the mitotic checkpoint protein Mad2, commonly found in human tumors, leads to CIN and the development of aneuploid tumors in mouse models. However, recent observations from various laboratories suggest that aneuploidy can promote or suppress tumorigenesis. Therefore understanding the relationship between aneuploidy and tumor formation, identifying in what context aneuploidy acts oncogenically and those in which it acts as a tumor suppressor, is thus vital if we want to make progress in battling cancer. We propose to generate regulatable mouse models that recapitulate the aneuploidy state of human tumors, using state-of–the–art mouse genetic strategies, to investigate the role of CIN in promoting or suppressing tumorigenesis. Moreover, CIN has been shown to facilitate escape from oncogene addiction (the dependence of tumor cells on their initiating lesion for survival) and may be responsible for tumor relapse after targeted therapies. Due to the clinical relevance of these findings, this proposal aims to investigate how CIN potentiates oncogene independence. It is possible that some CIN cells in the primary tumor are already independent of the initiating oncogene prior to treatment. Alternatively, CIN cells are more susceptible of acquiring additional mutations and evolve to become independent of the initiating lesion. We propose to develop a highly innovative three-dimensional in vitro culture system to isolate and characterize these surviving cells to further eliminate them. It is necessary to understand the molecular mechanisms that lead to CIN and the consequences it has in tumor initiation, suppression and relapse, hoping that the genes or proteins identified could be targeted therapeutically. We believe that answers to these specific aims will have important consequences for the treatment of human tumors.

Keywords: chromosome instability,aneuploidy,targeted therapies,oncogene addiction,mitotic checkpoint,mad2