Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Microbial Ecology of the DEep Atlantic pelagic realm (MEDEA)

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-2010-AdG_20100317, 2010)
Start date: 2011-07-01
End date: 2016-06-30
Duration (months): 60.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

The project aims at elucidating a major enigma in microbial ecology, i.e., the metabolic activity of prokaryotic communities in the deep sea under in situ pressure conditions, rather than under surface pressure conditions, as commonly done. Analysis of the global data set of prokaryotic abundance indicates that about 40% of prokaryotes reside in depth below 1000m depth with a phylogenetic composition different from that in surface waters. Using a recently fabricated high-pressure sampling and incubation system in combination with advanced tools to assess phylogenetic diversity, gene expression and single-cell activity, we will be able to resolve this enigma on a prokaryotic community level as well as on a phylotype level. This detailed knowledge on the distribution of the auto- and heterotrophic activity of deep-sea prokaryotes under in situ pressure conditions is essential to refine our view on the oceanic biogeochemical cycles, and to obtain a mechanistic understanding of the functioning of deep-sea microbial food webs.

Keywords: marine microbial ecology
Post-copulatory sexual selection in birds: sperm production, sperm selection and early development in birds (PCSSIB)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2017-04-30
Duration (months): 72.0
Total project cost (EUR): 1700000.0
EU funding (EUR): 1700000.0
Participants: 1
Project status: CLOSED

Sexual reproduction is one of the most fundamental of biological processes: (i) the creation of gametes, (ii) their fusion and (iii) the formation of a viable embryo are all shaped by a major evolutionary force: post-copulatory sexual selection comprising sperm competition and cryptic female choice. This project will make substantial advances in all three areas, using birds (mainly zebra finch) as model organisms. (i) Sperm size and shape: A major hypothesis for the enormous variation across species in the design of male gametes is that a trade-off exists between sperm size and number. We will test this, by estimating (for the first time) the energetic costs of making sperm. (ii) Sperm-female and sperm-egg interactions. We will establish, how sperm from different males interact within a female and will do this, uniquely, by using transgenic zebra finches whose sperm flagella are labelled with green fluorescent protein (GFP). This allows us to distinguish (in the oviduct and in ova) the sperm from GFP- and normal males and to visualise how they interact to generate last male sperm precedence. (iii) The genetic and environmental causes of embryo mortality. We will explore the environmental effects of temperature on embryo development and survival and consider the special case of brood parasites that expose their ova to elevated temperatures through ¿internal incubation¿. We will explore the genetic effects of DNA integrity, aneuploidy and compatibility on embryo survival. Together, these three interconnected strands will revolutionise the study of reproduction, answering the most outstanding questions in the field through a combination of novel techniques and novel hypotheses.

Keywords: post-copulatory sexual selection
Synaptic multi-factor learning rules: from action potentials to behaviour (MULTIRULES)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Switzerland
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2449218.0
EU funding (EUR): 2449218.0
Participants: 1
Project status: CLOSED

If we are ever to unravel the mysteries of learning, we need a strong theoretical framework that will enable us to trace behavioural properties of memory formation and action learning back to rules for changes of synaptic connections. Experiments on the cell and microcircuit level need hypothesis from theory in order to drive the experimental search for plasticity rules and organize the vast amount of data collected in different labs across Europe and the world. Potential links between synaptic plasticity rules and behavioural outcomes need to be established by mathematical analysis and computer simulation on the systems level, and could ultimately also lead to novel therapeutical approaches. Both theoretical and experimental approaches to synaptic plasticity have been dominated, in the past 30 years, by Hebb¿s rule but the Hebbian framework is a limitation, because it focuses only on two factors: the activity of the presynaptic (sending) neuron and that of the postsynaptic (receiving) one. Hence it neglects additional factors, such as non-specific neuromodulators or global activity states of brain areas. Only very recently a few experiments have appeared that study STDP in the presence of neuromodulators. In this project, I want to break with the preoccupation of Hebbian rules, and formulate and study rules of synaptic plasticity that combine the two Hebbian activity factors with one or multiple global factors. With the new theoretical framework for multi-factor learning rules, to be developed in this project, I will be able to guide the design of novel experiments so that experimental paradigms probe parameters that are relevant for learning. I will be able to make predictions for functional outcomes of learning on the behavioural level, and possibly provide novel strategies for learning of new memories, or unlearning of unpleasant ones.

Keywords: computational neuroscience,modeling,theory,learning rules,hebbian learning,spike-timing-dependent plasticity,neuromodulator,reward,associative memory
APL a model for oncogene-targeted leukemia cure (STEMAPL)

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: France,Lebanon
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-07-01
End date: 2017-06-30
Duration (months): 72.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 2
Project status: CLOSED

Acute promyelocytic leukaemia, APL, is probably one of the best-understood malignancies and the only one where highly efficient oncogene-targeted therapies (retinoic acid and arsenic) actually cure the disease. Our recent studies have addressed the molecular basis for transformation and demonstrated the essential role of sumoylation of the PML moiety of PML/RARA, relaxed DNA-binding specificity, binding to RXRA, for both transcriptional repression and transformation in primary cells, uncovering an unexpected level of complexity for in vivo transformation. We have also explored PML nuclear bodies (NB) formation, enigmatic structures that are disrupted by PML/RARA expression, restored by either RA or arsenic and may thus contribute to transformation/response. Exploring the actual basis for therapy response, we have provide some evidence that PML/RARA degradation and loss of leukaemia-initiating cells, rather than differentiation, is key to APL clearance. We propose to address the following issues: i) genetically uncouple differentiation from APL eradication ii) model transformation and therapy response iii) analyse the regulation and role of PML NBs iv) explore other models where degradation of the driving oncogene may eradicate the disease through loss of LIC activity. These studies should not only provide a complete model for APL pathogenesis and treatment response, but also open new avenues in the field of PML nuclear body biogenesis and function, as well as transcriptional activation/degradation coupling. The proposed research could provide generally applicable strategies for a variety of malignancies that are similarly driven by fusion proteins. As previously, in the APL and Adult T cell leukaemia models, our studies could also yield new directly clinically applicable therapeutic strategies.

Keywords: proteolysis,nuclear organisation,nuclear receptors,therapeutic modeling in vivo,translational research
The Evolution of Human Languages (MOTHERTONGUE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 1999973.0
EU funding (EUR): 1999973.0
Participants: 1
Project status: CLOSED

Human languages evolve by a process of cultural evolution in which linguistic varieties compete for our attention and adapt to the environment of our minds. This has produced a remarkable cultural replicator whose fidelity of transmission can rival that of some genes. Yet progress in understanding this defining human trait is impeded by an influential view that the processes of linguistic change are so rapid, idiosyncratic and many that general evolutionary rules and laws describing language evolution and language histories will not be found. That perspective can be contrasted with results emerging from recent empirical studies that point to simple and general rules of language evolution that have held throughout human history. This research programme is designed to bridge the gap in these perspectives. Our goal is to build and apply to real-world data, statistical models of linguistic evolution that will put the study of language change on a footing comparable to that of molecular evolution. Micro-evolutionary studies will formulate and test population-linguistic models of cultural selection acting on words competing within populations of speakers. Macro-evolutionary or comparative studies will build a novel probabilistic model of sound changes and apply it to reconstructing ancestral lexical forms (the proto-language) and language histories. Shared-process studies link these two levels, investigating how common patterns of word-usage and sound changes mediate language evolution around the globe. Our studies are relevant to questions of language competition and extinction and we will investigate how words evolve, reconstruct proto-languages and infer deep linguistic histories -- such as the linguistic settlement of Eurasia, and search for evidence of a Mother Tongue.

Keywords: language evolution,cultural evolution,adaptation,ancestral states,proto-language,word-use,'population linguistics',bayesian modelling,natural selection
The genomic blueprint of macrophages: dissecting players and mechanisms through an integrative approach (NORM)

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: Italy
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2016-05-31
Duration (months): 60.0
Total project cost (EUR): 2436200.0
EU funding (EUR): 2436200.0
Participants: 1
Project status: CLOSED

Macrophages are highly specialized cells widely distributed in tissues and active both as immune effectors and as housekeeping phagocytes responsible for maintenance of tissue integrity. Macrophages display a striking heterogeneity that reflects a complex interplay between different micro-environmental signals provided by various tissues (as well as by microbial and endogenous stress signals), and a robust differentiation program that determines macrophage identity. Terminal differentiation depends on the implementation of cell type-specific gene expression programs driven by fate-determining transcription factors (TF). However, the intermediate events linking lineage-specific TFs to the acquisition of the 1- and 3-dimensional genomic organization characteristic of a given cell type (and essential to configure its specific properties and its ability to properly react to the environment) are largely unknown. The objective of this project is to understand how macrophage identity, functional specialization and plasticity are controlled by their specialized genomic organization, which is encoded in mammalian genomes, controlled by specific TFs, and modulated by the microenvironment. By integrating cutting-edge biochemical and genomic techniques, genetics in the mouse, computational approaches and equilibrium thermodynamics, the project aims at describing, and mechanistically deciphering, the specific organization and usage of the genome that is characteristic of macrophages and underlies the acquisition of their functional properties. The output of the project will include concepts and paradigms widely exportable to other cellular systems.

Keywords: macrophages,inflammation,gene expression,enhancers,equilibrium thermodynamics,pu.1
The Role of Arl Proteins in Retinal and other Ciliary Diseases (ARCID)

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: Germany
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-04-01
End date: 2016-03-31
Duration (months): 60.0
Total project cost (EUR): 2434400.0
EU funding (EUR): 2434400.0
Participants: 1
Project status: CLOSED

Arl (Arf-like) proteins, GTP-binding proteins of the Ras superfamily, are molecular switches that cycle between a GDP-bound inactive and GTP-bound active state. There are 16 members of the Arl subfamily in the human genome whose basic mechanistic function is unknown. The interactome of Arl2/3 includes proteins involved in retinopathies and other ciliary diseases such as Leber¿s Congenital Amaurosis (LCA) and kidney diseases such as nephronophthisis. Arl6 has been found mutated in Bardet Biedl Syndrome, another pleiotropic ciliary disease. In the proposed interdisciplinary project I want to explore the function of the protein network of Arl2/3 and Arl6 by a combination of biochemical, biophysical and structural methods and use the knowledge obtained to probe their function in live cells. As with other subfamily proteins of the Ras superfamily which have been found to mediate similar biological functions I want to derive a basic understanding of the function of Arl proteins and how it relates to the development and function of the ciliary organelle and how they contribute to ciliary diseases. The molecules in the focus of the project are: the GTP-binding proteins Arl2, 3, 6; RP2, an Arl3GAP mutated in Retinitis pigmentosa; Regulators of Arl2 and 3; PDE¿ and HRG4, effectors of Arl2/3, which bind lipidated proteins; RPGR, mutated in Retinitis pigmentosa, an interactor of PDE¿; RPGRIP and RPGRIPL, interactors of RPGR mutated in LCA and other ciliopathies; Nephrocystin, mutated in nephronophthisis, an interactor of RPGRIP and Arl6, mutated in Bardet Biedl Syndrome, and the BBS complex. The working hypothesis is that Arl protein network(s) mediate ciliary transport processes and that the GTP switch cycle of Arl proteins is an important element of regulation of these processes.

Keywords: gtp binding protein,structure-function
The Genetics and Physiology of Growth and Size Determination (GROLEO)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: ERC Advanced Grant Interdisciplinary Panel
Countries involved: France
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-07-01
End date: 2016-06-30
Duration (months): 60.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

Animal growth is a complex process that is intimately linked to the developmental program in order to form fit adults with proper size and proportions. Genetics is an important determinant of growth, exemplified by the role of local diffusible molecules in setting organ proportions for a given species. In addition to this genetic control, organisms use adaptation mechanisms allowing modulating the size of individuals according to environmental cues, among which nutrition. Therefore, sophisticated cross-talks between local and global cues are at play for the determination of the final size of an individual. The major objective of this project is to tackle the mechanisms involved in coupling growth control with environmental cues, as well as the mechanisms participating in growth arrest and the determination of final size. Our project proposes a blend of physiological and genetic approaches on the Drosophila model, with the use of tissue-targeted loss-of-function to unravel some of the important cross-talks existing between organs for the control of growth at the global level. We will develop these approaches to (i) unravel the molecular nature of tissue cross-talks involved in nutrient sensing and the control of insulin/IGF secretion; (ii) tackle the feed-back mechanisms linking the developmental clock to the growing state of tissues and organs. These projects should bring new contributions in two separate fields related to growth control, Developmental Biology and Physiology, in an attempt to merge these complementary approaches into a broader vision of this fascinating biological question.

Keywords: growth control,insulin,insulin-like growth factors,ecdysone,genetics,development,physiology,drosophila
Interplay of genetic, nutrient and lifestyle factors on incidence of coronary disease: EPIC-Heart (EPICHEART)

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,United Kingdom,Norway
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2017-04-30
Duration (months): 72.0
Total project cost (EUR): 2499154.4
EU funding (EUR): 2499154.4
Participants: 3
Project status: CLOSED

A major new frontier in biomedicine is to identify interactions of specific components of nature and nurture in determining risk of complex diseases. Coronary heart disease (CHD) - the single leading cause of death in Europe - is jointly determined by genetic and lifestyle factors. It is unknown, however, how diet, nutrients, and lifestyle factors modulate genetic susceptibility. For scientific and public health reasons, there is a strategic need to study such interactions reliably. There is a unique opportunity for a cost-effective and powerful study because we have: -conducted detailed assessment of diet and other lifestyle factors in 520K participants in a pan-European prospective study -identified >12K incident CHD cases accrued during >5M person-years at risk -identified a random sub-cohort of >15K participants without CHD to serve as referents -commenced assay of lipid and other markers in 12K cases and 15K referents -prepared DNA for genetic assay. In 12K CHD cases and 15K referents, we will assay: >217K genetic variants contained in the state-of-the-art metabochip; 37 fatty acids; and vitamin D metabolites. Analyses will focus on: discovery of interactions; causal evaluation of biomarkers; CHD risk scores. The findings should open new horizons and contribute towards: 1) explaining missing heritability 2) shaping nutritional guidelines 3) personalising preventive medicine 4) defining approaches to modify genetic susceptibility by avoiding deleterious lifestyles 5) identifying biomarkers that are priority therapeutic targets and 6) innovative prognostic tools. Gene-lifestyle interplay is a major future growth area. This world-leading study will enhance Europes strengths in public health, nutrition and genetic epidemiology, and create a valuable future resource.

Keywords: epidemiology,cardiovascular,risk factors,interactions
Resistance systems and population structure of parasites (RESIST)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: Switzerland
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2100000.0
EU funding (EUR): 2100000.0
Participants: 1
Project status: CLOSED

The study of parasitism is important for human welfare but also addresses basic scientific questions cutting across biological disciplines. Traditionally, studies of host-parasite interactions have used various scenarios of how genotypes of the two parties interact based on well-developed theory. Yet, one of the most striking observations is the huge variation in resistance systems across organisms. We lack an appreciation of the diversity of these resistance systems and how they affect, in turn, the parasites. Here, it is proposed to investigate the hypothesis that variation in gene expression is a key element that defines an alternative, flexible and highly adaptable resistance system. The project attempts to unify genomic studies of defence mechanisms with questions of evolutionary ecology of host-parasite interactions. Therefore, the study focuses on an ecologically well-studied system of hosts (Bombus spp.) and their prevalent trypanosome infections (Crithidia). In this system, a highly genetically polymorphic parasite is kept in check by a host with seemingly conserved immune effectors (e.g. anti-microbial peptides, AMPs). Their expression varies depending on the host-parasite pairing, suggesting that variation of the synergistic mixture of expressed defence elements might be crucial and could affect parasite population structure in turn. In the project, experiments and cutting-edge molecular methods will be applied to a natural host-parasite system.

Keywords: host-parasite interaction,ecological immunology,anti-microbial peptide,expression,pollinator,trypanosome