Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Parasite population genomics and functional studies towards development of a blood stage malaria vaccine (GENINVADE)

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: United Kingdom,Mali,United Kingdom,Senegal,Ghana
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-07-01
End date: 2017-06-30
Duration (months): 60.0
Total project cost (EUR): 2948083.0
EU funding (EUR): 2948083.0
Participants: 5
Project status: CLOSED

An effective malaria vaccine is needed, particularly against P. falciparum as this species causes more human mortality than all other eukaryotic pathogens combined. An understanding of natural selection operating on parasites in local endemic populations can enable understanding of core molecular mechanisms of global relevance. The objectives are to - Advance understanding of alternative pathways of erythrocyte invasion by malaria parasites - Advance understanding of immune evasion by malaria parasites - Identify optimal combinations of parasite proteins as malaria vaccine candidates - Develop the interface between population genomic and functional studies of malaria parasites The research programme will take an integrated approach to understanding pathogen adaptation, by designing experiments that are based on analysis at the molecular, functional, and population levels. (i) Population genetic analyses of P. falciparum in sites of contrasting endemicity in West Africa, to finely determine signatures of selection with high-resolution throughout the genome, and help refine hypotheses on mechanisms used by merozoites to invade erythrocytes and evade acquired immune responses. (ii) Experimental culture analysis of merozoite invasion into erythrocytes to identify the receptor-ligand interactions used by different parasite populations ex vivo. Novel receptor knockdown assays on cultured erythrocytes will be employed, and parasite adaptation experiments conducted to identify constraints on the use of alternative invasion pathways (iii) Innovative approaches to select individual parasites and characterise cell tropism, transcript profiles, and genome sequences. This is aimed to validate population level findings and revolutionise approaches to genetics and phenotyping of parasites in the future. Candidate molecule discoveries will be taken forwards to receptor-ligand interaction assays, antibody inhibition and immuno-epidemiological studies.

Keywords: erythrocyte invasion,immunity,adaptation,selection
Enzymatic and genomic targets of histone modifying enzymes and their role in liver metabolism and hepatocarcinogenesis. (SET-NET)

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: Greece
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 2499600.0
EU funding (EUR): 2499600.0
Participants: 1
Project status: CLOSED

In this proposal we will study the role of histone methytransferases Set9, PR-SET7, Smyd2, Smyd3 and the demethylase LSD1 in hepatocarcinogenesis and in the regulation of hepatic metabolic pathways. The hypothesis raised here suggests that the function of histone modifying enzymes is realized through 4 overlapping regulatory layers: i. via modifications of chromatin, ii. via modifications of recently identified transcription factor substrates, iii. via influencing the hepatic transcription factor crossregulatory circuitry, and iv. via modification of each other. To dissect the role of these regulatory layers and determine their contribution in the control of hepatic metabolic pathways, and in the development of hepatocellular carcinoma, our activities will involve: i. Generation of relevant KO and transgenic mouse models, ii. Functional characterization of novel non-histone and histone substrates, iii. Analysis of novel cross-regulatory protein modifications affecting the activity of the enzymes and iv. the identification of their genomic targets and associated chromatin modifications using global approaches. The work is expected to provide important insights into a previously unanticipated network of protein methylation-directed regulatory modules, potentially operating in multiple biological pathways such as liver development, metabolism, apoptosis and carcinogenesis. The functioning of such network would be of high biological importance, with far-reaching implications in drug development, rivaling those of phosphorylation or acetylation regulated processes.

Keywords: histone methylase,histone demethylase,liver,epigenetic regulation,hepatocarcinogenesis,hepatic metabolic pathways
Construction of Perception from Touch Signals (CONCEPT)

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: Italy
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-06-01
End date: 2018-05-31
Duration (months): 72.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

Our sensory systems gather stimuli as elemental physical features yet we perceive a world made up of familiar objects, not wavelengths or vibrations. Perception occurs when the neuronal representation of physical parameters is transformed into the neuronal representation of meaningful objects. How does this recoding occur? An ideal platform for the inquiry is the rat whisker sensory system: it produces fast and accurate judgments of complex stimuli, yet can be broken down into accessible neuronal mechanisms. CONCEPT will examine the process that begins with whisker motion and ends with perception of the contacted object. Understanding the general principles for the construction of perception will help explain why we experience the world as we do. The main hypothesis is that graded neuronal representations at early processing stages are “fractured” to generate discrete object representations at late processing stages. Of particular interest is the emergence of object representations as the meaning of new stimuli is acquired. We will collect multi-site single-unit and local field potential signals simultaneously with precise behavioral indices, and will interpret data through advanced computational methods. We will begin by quantifying whisker motion as rats discriminate texture, thus defining the raw material on which the brain operates. Next, we will characterize the transformation of texture along an intracortical stream from sensory areas (where we expect that neurons encode whisker kinematics) to frontal and rhinal areas (where we expect that neurons encode objects extracted from the graded physical continuum) and hippocampus (where we expect that neurons encode objects in conjunction with context). We will test candidate processing schemes by manipulating perception on single trials using optogenetic methods.

Keywords: neocortex,hippocampus,tactile
Mismatch repair interactome and mutagenesis (MIRIAM)

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: Switzerland
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-04-01
End date: 2016-08-31
Duration (months): 53.0
Total project cost (EUR): 2208084.0
EU funding (EUR): 2208084.0
Participants: 1
Project status: CLOSED

The mismatch repair (MMR) system has evolved to correct errors of DNA replication and prevent recombination between non-homologous sequences. Correspondingly, MMR malfunction leads to increased mutation rates and illegitimate recombination, and individuals with inherited MMR gene mutations are predisposed to cancer of the colon and other organs. However, MMR has recently been implicated in processes ranging from DNA damage signaling and drug sensitivity to antibody maturation, some of which contradict and even subvert the classical role of MMR as a guardian of genomic integrity. We suspect that the latter processes are linked to a new, non-canonical MMR (ncMMR) pathway that can be activated outside of the S- and G2 phases of the cell cycle by a variety of lesions and structures. ncMMR lacks strand directionality, involves long stretches of DNA degradation, and our preliminary in vitro evidence suggests that resynthesis of these repair tracts can be mediated not only by high-fidelity, replicative polymerases, but also by error-prone enzymes. In this scenario, ncMMR would actually contribute to mutagenesis. I plan to deploy proteomic, genomic and imaging technologies to identify the components of the ncMMR “mutasome” and to reconstitute the system from purified recombinant components. Furthermore, I wish to study the “action radius” of MMR proteins by characterizing their interactome and analyze its dependence on endogenous states (e.g. cell cycle stages) and exogenous stimuli (e.g. drug treatments) in human and chicken (DT40) cells, and Xenopus laevis egg extracts. I intend to exploit a new system of inducible protein replacement that was recently developed in my laboratory, to stably express MMR, replication, repair and recombination proteins (both wild type and variants). This program should increase our understanding of the pivotal role of MMR in DNA metabolism and its involvement in human disease and cancer.

Keywords: mismatch repair,mutagenesis,base excision repair,genomic instability,somatic hypermutation,class switch recombination.
Assembling the puzzle of the operating auditory hair bundle (HAIRBUNDLE)

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: France
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-12-01
End date: 2018-08-31
Duration (months): 69.0
Total project cost (EUR): 2495000.0
EU funding (EUR): 2495000.0
Participants: 1
Project status: CLOSED

The hair bundles of the sensory cells play a central role in the processing of sounds by the cochlea. Various performances of auditory perception depend upon what biophysical and physiological environment the operating hair bundle can provide to its mechanoelectrical transduction (MET) channels. The project aims at building a more integrated view of the way the hair bundle works. Reaching this goal, requires to understand the interdependence of its functional building blocks and their dynamic interplay. To this purpose, the objectives of the work are : 1. To assemble components of the basal MET machinery The work aims at a) identifying the molecular players of the basal MET machinery, most of which are still unknown b) deciphering their functional interactions, c) developing a simple and efficient tool to validate candidate components of the MET machinery. 2. To elucidate the coupling between MET and stereocilia F-actin polymerisation The work aims at a) characterising this coupling, both in development and in steady-state condition, b) deciphering the role of tip-link tension and Ca+2 influx through the MET channel, c) developing a coarse-grained mathematical model of this coupling, experimentally testable. 3. To understand the interplay between MET, waveform distortions, and masking The work aims at a) deciphering biochemical characteristics of the top connectors, b) explaining why large waveform distortions vanish in the absence of top connectors, c) determining how the operating outer hair cell (OHC) hair bundle contributes to the masking effect in auditory perception. The hair bundle is a highly vulnerable structure, actually the main target structure of noise-induced hearing loss and hereditary deafness forms. As such, advances in the understanding of the mechanisms underlying its functioning will pave the way for the development of therapeutic approaches.

Keywords: cochlea,human hereditary hearing impairment,hair cells,mechano-electrical transduction
Next generation disease resistance breeding in plants (NGRB)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: United Kingdom
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-04-01
End date: 2017-03-31
Duration (months): 60.0
Total project cost (EUR): 2496835.0
EU funding (EUR): 2496835.0
Participants: 2
Project status: CLOSED

Plant diseases represent a significant threat to global food security. One of the most notorious plant pathogens is the Irish potato famine organism Phytophthora infestans. P. infestans, the causal agent of potato and tomato late blight, continues to cost modern agriculture billions of euros annually. The most sustainable strategy to manage late blight is to breed broad-spectrum disease resistance into potato and tomato. However, current disease resistance breeding approaches are slow, inefficient, and have taken little advantage of emerging knowledge of pathogen mechanisms. Resistance genes have been identified, bred, and deployed in agriculture without detailed knowledge of the effectors they are sensing – a ‘blind’ approach. The overall aim of this proposal is to exploit state of the art findings on pathogen effector biology to drive the development of new approaches to breeding disease resistant crops. Our long-term objective is to generate late blight resistant crop varieties. The central hypothesis of the proposed research is that mutations in plant resistance and effector target genes can result in broad-spectrum resistance to late blight. The rationale behind this research is based on exciting preliminary data that demonstrated (i) there is a core set of effectors in P. infestans; (ii) plant proteins targeted by P. infestans effectors are important components of the immune response; and (iii) single amino acid changes in a potato resistance protein can result in expanded effector recognition. To achieve our goal, we plan to pursue the following specific objectives: 1. Understand the molecular details of how three P. infestans effectors modulate plant immunity. 2. Generate synthetic plant resistance genes with expanded recognition of P. infestans effectors. 3. Generate synthetic plant effector targets with modified interaction with P. infestans effectors. 4. Use the synthetic genes to engineer broad-spectrum late blight resistance.

Keywords: applied life sciences and biotechnology
EPidemiological Left ventriclar Outcomes Research in Europe (EPLORE)

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: Belgium
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-07-01
End date: 2017-06-30
Duration (months): 60.0
Total project cost (EUR): 2391440.0
EU funding (EUR): 2391440.0
Participants: 1
Project status: CLOSED

Heart failure (HF) affects 15 million Europeans and entails higher mortality and health care costs than cancer. EPLORE addresses this issue by prospective epidemiological research in 4 European countries and by a proof-of-concept clinical trial. WP1 will for the first time at the population level document the incidence and progression of subclinical LV dysfunction and clarify whether asymptomatic LV dysfunction, as picked up by the newest echocardiographic techniques, predicts cardiovascular (CV) outcomes, including HF. WP2 will investigate the contribution of ventricular-arterial coupling disease and mechanical LV dyssynchrony to subclinical LV dysfunction. WP3 will identify a set of urinary polypeptides that signify early LV dysfunction and validate these biomarkers by showing that they predict deterioration of LV function, progression to HF and the incidence of CV complications over and beyond established risk factors. WP3 will also search for novel panels of circulating biomarkers, of which combined measurement will add information (accuracy, sensitivity and specificity) to established biomarkers (e.g., NT-proBNP) and identify genetic variants involved in the progression of LV dysfunction, either causally or as biomarker. WP4 consists of a randomised clinical trial to translate in a high-risk high-gain setting the results of WPs 1-3 into clinical practice and to identify a new treatment modality that potentially slows progression of diastolic LV dysfunction. Dissemination in WP5 will contribute to new guidelines for the prevention and treatment of HF. WP6 includes governance, monitoring research strategies and output, and protection of IPR. In conclusion, EPLORE will advance risk stratification and the early diagnosis of subclinical HF. The project will potentially result into specific treatments for diastolic LV dysfunction and inform guidelines for prevention and treatment of HF. It will benefit 20% of Europeans who currently have subclinical LV dysfunction.

Keywords: left ventricular function,heart failure,population science,urinary proteomics,proof-of-concept clinical trial,morbidity,mortality
International Foresight Academy (IFA)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Research Staff Exchange Scheme
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Austria,Austria,Switzerland,Romania,United Kingdom,Finland,Israel
Call:  (FP7-PEOPLE-2011-IRSES, 2011)
Start date: 2012-05-01
End date: 2015-04-30
Duration (months): 36.0
Total project cost (EUR): 391300.0
EU funding (EUR): 368500.0
Participants: 7
Project status: CLOSED

The proposed International Foresight Academy is the first organization to bind together Foresight activities around the globe and from contrasting cultural and political contexts. As the Mapping Report of the European Foresight Monitoring Network (2009) has documented, Foresight is used differently in various regions of the world. Foresight activities vary according to sponsors and customers, methods used, topics explored, actors involved etc. They vary also with regard to their functions in political strategy formulation of modern democracies. During the past 30 years in Europe, Foresight has become an unconventional means of political priority setting and strategic decision making that affect a wide set of societal stakeholders. The added value of foresight is seen in the shared goals and visions among a group of participating actors from different sectors, the development of networks, and the combination of relevant information on current trends and future developments with actor-based information and attitudes. Many foresight practitioners value the possibility granted by foresight exercises to bring topics on the political agenda that need to be discussed not behind closed doors but with broad public involvement. The proposal for the IFA consists two parts: a research part dedicated to the issue of FS as a format of participation in different democratic traditions; and a second part that manages the networking of the partners doing research on the FS field with regard to democracy and participation. The network will involve activities such as mutual exchange among the partners, summer/winter schools for early stage researchers, seminars and academic workshops. The outreach of some of these activities will address additional actors as well, e.g. stakeholders, organizers, practitioners of FS exchanging knowledge in the envisaged conferences.

Keywords: foresight,innovation,participation,comparative research,social sciences
CHARACTERIZATION AND SUSTAINABLE USE OF EGYPTIAN DEGRADED SOILS (SUDSOE)

Framework: FP7 — Capacities
Programme: Activities of International Cooperation
Destination: Reinforcing cooperation with Europe's neighbours in the context of the ERA
Action type: Coordination and support actions
Countries involved: Egypt,Spain,Sweden,Czechia
Call:  (FP7-INCO-2011-6, 2011)
Start date: 2012-01-01
End date: 2014-12-31
Duration (months): 36.0
Total project cost (EUR): 531777.88
EU funding (EUR): 499195.0
Participants: 4
Project status: CLOSED

SUDSOE intends to increase the scientific regional leadership, to pursue, transfer, and provide the most advanced technology in the fields of remote sensing and peaceful application of space sciences applied to the characterization and sustainable use of Egyptian degraded soils, and build the self-capability to utilize these technologies to support the National development activities. Such challenges will be achieved through reinforcing its excellence and creativity contributing to regional economy and social welfare in line with EU2020 Strategy, which sets priorities on developing an economy based on knowledge and innovation. NARSS demonstrate high level of human, material and organizational capacity as well several collaboration experiences with European and African countries, but SWOT analysis indicates some weaknesses to be faced in order to reach the scientific regional leadership. Based on the SWOT analysis and in accordance with the Work Program of the call, coherent set of measures are elaborated. Full research potential will be realized in close cooperation with 3 outstanding EU partnering organisations (POs) in the same S&T domain. The NARSS human will be enhanced by: developing strategic partnership with POs, by transferring and sharing of experience and knowledge; - recruitment of experienced researchers to prevent brain drain; - dissemination and promotion of acquired knowledge at national, regional and international level, especially in the MED region. SUDSOE outcome is related to diverse beneficiaries, such as scientific community, general public, local authorities, policy makers and diverse stake-holders.

Keywords: capacity building,sustainable use of degrade soils,characterization of polluted soils,heavy metals,nanotechnology,humic and fulvic acids,regional leadership,remote sensing sciences