Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Exploring the gamma-ray sky: binaries, microquasars and their impact on understanding particle acceleration, relativistic winds and accretion/ejection phenomena in cosmic sources. (GAMMARAYBINARIES)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Systems and communication engineering
Countries involved: France
Call:  (ERC-2007-StG, 2007)
Start date: 2008-07-01
End date: 2013-06-30
Duration (months): 60.0
Total project cost (EUR): 794752.0
EU funding (EUR): 794752.0
Participants: 1
Project status: CLOSED

The most energetic photons in the universe are produced by poorly known processes, typically in the vicinity of neutron stars or black holes. The past couple of years have seen an increase in the number of known sources of very high energy gamma-ray radiation from a handful to almost 50, thanks to the European collaborations HESS and MAGIC. Many of those sources are pulsar wind nebulae, supernova remnants or active galactic nuclei. HESS and MAGIC have also discovered gamma-ray emission from binary systems, finding that some emit most of their radiation at the highest energies. Expectations are running high with the December launch of the GLAST space telescope which will provide daily all-sky information in high energy gamma-rays with a sensitivity comparable to that achieved in years by its predecessor. I propose to explore the exciting observational opportunities in high energy gamma-ray astronomy with an emphasis on non-thermal emission from compact binary sources. Binary systems are intriguing new laboratories to understand how particle acceleration works in cosmic sources. The physics of gamma-ray emitting binary systems is related to that in pulsar wind nebulae or in active galactic nuclei. High energy gamma-ray emission is the result of non-thermal, out-of-equilibrium processes that challenge our intuitions built upon everyday phenomena. The particles are billions of times more energetic than X-rays and can reach energies greater than those in particle accelerators. Binary systems offer a novel, constrained environment to study how the cosmic rays that pervade our Galaxy are accelerated and how non-thermal emission is related to the formation of relativistic jets from black holes (accretion/ejection). The study requires a combination of skills in multiwavelength observations, interdisciplinary experience with gamma-ray observational techniques originating from particle physics, and theoretical know-how in accretion and high energy phenomena.

Keywords: gamma-rays,jets,microquasars,pulsars,accretion,accretion disks
Genetic Record of Atmospheric Carbon dioxidE (GRACE) (GRACE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Products and process engineering
Countries involved: United Kingdom
Call:  (ERC-2007-StG, 2007)
Start date: 2008-09-01
End date: 2015-08-31
Duration (months): 84.0
Total project cost (EUR): 1652907.0
EU funding (EUR): 1652907.0
Participants: 1
Project status: CLOSED

Two key variables, temperature and atmospheric carbon dioxide (pCO2), define the sensitivity of the Earth’s climate system. The geological record provides our only evidence of the past climate sensitivity of the Earth system, but there is no direct quantitative measure of pCO2 or temperature beyond the 650 kyr extent of the Antarctic ice cores. The reconstruction of past climate, on timescales of millions of years, relies on the analysis of chemical or isotopic proxies in preserved shells or organic matter. Such indirect approaches depend upon empirical calibration in modern species, without understanding the biological mechanisms that underpin the incorporation of the climate signal. The intention of this ERC grant proposal is to establish a research team to investigate the “living geological record” to address this major gap in climate research. I hypothesise that direct climate signals of the past are harboured within, and can ultimately be deciphered from, the genetic make up of extant organisms. Specifically, I propose an innovative approach to the constraint of the evolution of atmospheric pCO2 during the Cenozoic. The approach is based on the statistical signal of positive selection of adaptation within the genetic sequences of marine algal Rubisco, the notoriously inefficient enzyme responsible for photosynthetic carbon fixation, but supplemented by analysis of allied carbon concentrating mechanisms. As a calibration, I will characterise the biochemical properties of Rubisco in terms of specificity for pCO2, isotopic fractionation and kinetics, from a range of marine phytoplankton. The prime motivation is a history of pCO2, but the project will yield additional insight into the feedback between phytoplankton and climate, the carbon isotopic signatures of the geological record and the mechanistic link between genetic encoding and specific

Keywords: marine phytoplankton,photosynthesis,genetics,atmospheric carbon dioxide,climate sensitivity.
TARGETING HIV INTEGRATION CO-FACTORS, TARGETING CELLULAR PROTEINS DURING NUCLEAR IMPORT OR INTEGRATION OF HIV (THINC)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Belgium,Italy,Italy,South Africa,Czechia,Switzerland,Belgium,Ireland
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-03-01
End date: 2012-02-29
Duration (months): 48.0
Total project cost (EUR): 3899101.77
EU funding (EUR): 2939672.0
Participants: 11
Project status: CLOSED

Standard therapy of infection with the human immunodeficiency virus type 1 (HIV-1) is based on potent cocktails of drugs targeting viral proteins. This treatment is associated with severe side effects and is almost unaffordable for the patients living in sub-Saharan Africa. Incomplete suppression of HIV replication results in drug-resistance. Therefore, a continued research effort is required to develop more potent, cheaper and less toxic antivirals. The insight has grown that HIV requires cellular proteins to serve as co-factors for viral replication. Our over-all objective is to develop novel drugs by targeting co-factors required for HIV replication. The virus will find it difficult to develop antiviral resistance against drugs targeting interaction between invariable cellular proteins and conserved viral protein domains. We will focus on the cellular proteins that mediate HIV trafficking, nuclear import and integration, such as Lens Epithelium Derived Growth Factor (LEDGF/p75), a novel cofactor of HIV-1 integration. THINC is composed of 3 virologists, 2 medicinal chemists, 1 virologist from South Africa, 1 structural biologist, 1 pharmaceutical company. Our first objective is to identify and validate novel co-factors of HIV trafficking, nuclear import and integration as novel targets for anti-HIV therapy. The second objective is to develop new drugs against the validated cellular target LEDGF/p75. The third objective is to perform this work in the perspective of those who will benefit most: the HIV infected people all over the world. The initial steps of target validation and hit identification will mainly be taken by academic groups, while optimization and (pre)clinical development of drugs requires the participation of Tibotec, a European company devoted to the development of antiviral drugs. The project will also increase our generic understanding of protein-protein interactions (PPI).

Keywords: aids,co-factors,ledgf/p75,antiviral drugs,resistance,integration,import,protein protein interaction
Protein engineering for the study of detoxification enzymes and hub proteins (SULTENG)

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: Israel
Call:  (ERC-2007-StG, 2007)
Start date: 2008-07-01
End date: 2013-06-30
Duration (months): 60.0
Total project cost (EUR): 1000000.0
EU funding (EUR): 1000000.0
Participants: 1
Project status: CLOSED

Proteins that exhibit broad specificity play important roles in different biological processes. These proteins include enzymes that catalyse the chemical transformation of many different substrates and proteins that bind to multiple protein partners. We propose to develop and apply novel directed evolution and chemical genetic methodologies for the study of proteins that exhibit broad specificity, with focus on cytosolic sulfotransferases (SULTs), which detoxify a broad range of xeno- and endobiotics, and proliferating cellular nuclear antigen (PCNA), which binds to multiple protein partners to play a central role in DNA replication and repair. SULTs belong to a large family of detoxification enzymes that exhibit broad specificity and relatively poor catalytic efficiency. It is not clear how SULTs can detoxify a variety of different compounds and what constitutes the molecular basis for their broad specificity. Application of directed evolution methodologies will allow us to identify and isolate SULT mutants with improved catalytic efficiency and novel specificity. These mutants will be thoroughly characterised by applying a variety of biochemical and structural methodologies to provide new insights into the broad specificity, catalytic activity and biological functions of SULTs. In parallel, we propose to develop and apply directed evolution methodologies for the study of PCNA. PCNA is a homotrimeric hub protein that forms a DNA sliding clamp to mediate DNA replication and repair by recruitment of a variety of essential proteins to the DNA template. Very little is known about how these multiple binding choices are regulated or about the importance of the different PCNA-protein interactions at different stages of replication. We propose to generate PCNA mutants with new binding activity and novel specificity, followed by thorough in-vitro and in-vivo characterisation, to study the roles of PCNA-protein interactions in DNA replication and repair.

Keywords: protein engineering,directed evolution,high-throughput screening,broad-specificity,sulfotransferase (sult),proliferating cellular nuclear antigen (pcna),hub proteins,chemical genetics
Genomic stability -chromosome segregation and repair (GENOMIC STABILITY)

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: Sweden
Call:  (ERC-2007-StG, 2007)
Start date: 2008-09-01
End date: 2013-08-31
Duration (months): 60.0
Total project cost (EUR): 900000.0
EU funding (EUR): 900000.0
Participants: 1
Project status: CLOSED

The eukaryotic genome combines a highly dynamic nature with stable transmission of genetic information from mother to daughter cells. This is achieved by a plethora of protein networks regulating processes such as chromosome duplication, segregation and repair. The principal aim of our research is to determine the molecular interplay between chromosome segregation and repair. Accurate execution of these two events is crucial for the maintenance of genome stability, which in turn is essential for life. Additionally, erroneous segregation or repair leads to chromosomal aberrations that are linked to tumor formation and human developmental syndromes. Thus, our investigations are not only crucial in a basic research perspective, but important also for the understanding of the causes of human disease. The research is based on the budding yeast model system, and combines genome-wide analysis of protein-chromosome interactions with cell-based experimental systems. Our investigations have until now revealed that chromosome segregation and repair are directly linked through two evolutionary conserved SMC (Structural Maintenance of Chromosomes) protein complexes, Cohesin and the Smc5/6 complex. The project now further explores the molecular details of this connection, bringing light into this unexplored area of research, and deciphering the cellular defense against genomic alterations connected to cancer and developmental diseases.

Keywords: genome stability,chromosome segregation and repair,genome-wide analysis
ANTIBODY DERIVATIVES AS MOLECULAR AGENTS FOR NEOPLASTIC TARGETING (ADAMANT)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Italy,Switzerland,Germany,United Kingdom,Belgium,Netherlands,Italy
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-04-01
End date: 2011-03-31
Duration (months): 36.0
Total project cost (EUR): 3918400.0
EU funding (EUR): 3000000.0
Participants: 9
Project status: CLOSED

The selective delivery of bioactive agents (cytotoxics, radionuclides, cytokines) at the tumor site, while sparing normal tissues, represents one of the most promising avenues for the development of anticancer therapies with unprecedented efficacy and tolerability. Monoclonal antibodies represent the preferred vehicle for the targeted delivery of bioactive agents to cancer sites, as they can display a preferential accumulation in primary and metastatic tumor lesions already few hours after intravenous administration. Certain monoclonal antibody derivatives can remain on the neoplastic mass for several days, thus enabling the slow release of potent cytotoxics or the continuous action of bioactive agents such as cytokines or therapeutic radionuclides. The ADAMANT Project aims at the generation of anticancer agents of superior quality, which rely on the antibody-based delivery of cytotoxics, radionuclides or immunostimulatory cytokines to either vascular tumor antigens or to tumor cell membranes. While clinically-validated antibodies will allow the rapid development of therapeutic strategies based on novel antibody derivatives, innovative perfusion-based chemical proteomic technologies will facilitate the discovery of accessible and abundant tumor-associated antigens, ideally suited for the targeted delivery of bioactive agents to cancer sites. Imaging methodologies will guide us in the selection of antigens, antibodies and therapeutic agents with optimal pharmacokinetis and pharmacodynamics. Finally, therapy studies in tumor-bearing mice, featuring the use of antibody-derivatives in combination with other anti-cancer drugs (cytotoxic, biological, vascular disrupting agents) will provide insights about how to best translate the results of the ADAMANT Project to clinical development. The Project will be truly successful if at least one antibody-based tumor targeting agent enters full-blown industrial development programs by the end of the ADAMANT Project.

Keywords: antibody-drug conjugates,radioimmunotherapy,immunocytokines,vascular tumor targeting,combination therapy.
Unravelling the molecular basis of common complex human disorders using the dog as a model system (LUPA)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Belgium,Sweden,United Kingdom,Finland,Denmark,Norway,Netherlands,Switzerland,United Kingdom,France,France,France,Spain,Ireland,Germany,United Kingdom,United Kingdom
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-01-01
End date: 2012-06-30
Duration (months): 54.0
Total project cost (EUR): 15677376.24
EU funding (EUR): 11997994.0
Participants: 23
Project status: CLOSED

Despite major efforts, identifying susceptibility genes for common human diseases - cancer, cardiovascular, inflammatory and neurological disorders - is difficult due to the complexity of the underlying causes. The dog population is composed of ~ 400 purebred breeds; each one is a genetic isolate with unique characteristics resulting from persistent selection for desired attributes or from genetic drift / inbreeding. Dogs tend to suffer from the same range of diseases than human but the genetic complexity of these diseases within a breed is reduced as a consequence of the genetic drift and – due to long-range linkage disequilibrium – the number of SNP markers needed to perform whole genome scans is divided by at least ten. Here, we propose a European effort gathering experts in genomics to take advantage of this extraordinary genetic model. Veterinary clinics from 12 European countries will collect DNA samples from large cohorts of dogs suffering from a range of thoroughly defined diseases of relevance to human health. Once these different cohorts will be built, DNA samples will be sent to a centralized, high-throughput SNP genotyping facility. The SNP genotypes will be stored in central database and made available to participating collaborating centres, who will analyze the data with the support of dedicated statistical genetics platforms. Following genome wide association and fine-mapping candidate genes will be followed up at the molecular level by expert animal and human genomics centers. This innovative approach using the dog model will ultimately provide insights into the pathogenesis of common human diseases – its primary goal.

Keywords: genome wide association,snps,complex traits,disease mapping,human disease
European Network for Genetic and Genomic Epidemiology (ENGAGE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Finland,United Kingdom,Germany,United Kingdom,United Kingdom,Netherlands,Germany,Sweden,Sweden,Sweden,Norway,Estonia,Iceland,Canada,Spain,United Kingdom,Germany,Australia,Latvia
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-01-01
End date: 2012-12-31
Duration (months): 60.0
Total project cost (EUR): 16307324.2
EU funding (EUR): 12000000.0
Participants: 26
Project status: CLOSED

ENGAGE (European Network for Genetic and Genomic Epidemiology) has, as its central objective, the translation of the wealth of data emerging from large-scale research efforts in molecular epidemiology into information of direct relevance to future advances in clinical medicine. ENGAGE will do this through the integration of very large-scale genetic and phenotypic data already available from a substantial number of large and well-characterised European (and other) sample sets of various types. The initial focus will be an integrated analysis of &gt;80,000 genomewide association scans available to the consortium, thereby identifying the large number of novel disease-susceptibility variants undetectable in individual studies. Early studies will concentrate on metabolic and cardiovascular phenotypes, with subsequent expansion to apply the methods developed and lessons learned in other disease areas. The ENGAGE framework has been designed to be adaptable to advances that enable global analyses of other sources of genomic variation (eg structural and epigenetic variants), and to broadening of the phenotypic spectrum (to genomic endophenotypes in particular). The clinical and public health relevance of the novel disease- and trait-susceptibility variants we identify will be evaluated using the breadth and diversity of ENGAGE cohorts (DNAs and serum/plasma samples from over 600,000 individuals). The final step will be to effect responsible clinical translation of our major findings. As well as advances in the understanding of disease pathogenesis which may underpin novel therapeutic advances, we expect to provide clear proof-of-principle that genetic and genomic discoveries can be translated into diagnostic indicators for common diseases with the capacity to stratify risk, monitor disease progression and predict and monitor therapeutic response. ENGAGE has assembled the best researchers, clinical samples and statistical and technical expertise in Europe to realise these goals.

Keywords: molecular epidemiology,genomics,population cohorts,clinical translation,human health
Prostate cancer: profiling and evaluation of ncRNA (PROSPER)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Finland,Netherlands,United Kingdom,Sweden,Finland,United Kingdom,Denmark
Call:  (FP7-HEALTH-2007-A, 2007)
Start date: 2008-02-01
End date: 2012-07-31
Duration (months): 54.0
Total project cost (EUR): 3971688.64
EU funding (EUR): 2986216.0
Participants: 8
Project status: CLOSED

Annually, over 200 000 new prostate cancer cases are diagnosed in Europe. This number is expected to further increase due to widespread use of prostate specific antigen (PSA) tests on asymptomatic men and an aging population. This leads to high rate of over-detection, where most cases will never experience cancer symptoms during their lifetime. Hence, our current lack of means to predict prostate cancer prognosis will have devastating impact on both life-quality and health care expenditures. Molecular mechanisms of the development of prostate cancer are largely unknown apart from the recognized role of androgens. Lack of knowledge on mechanisms leading to the development and progression of this cancer hampers development of efficacious prevention, specific diagnostics, prognostic, and therapeutic tools. Based on the emerging knowledge on the function of non-coding RNAs (ncRNAs) as regulators of key cellular mechanisms and our own preliminary data on expression of ncRNAs in prostate cancer, it is very likely that ncRNAs are involved in the tumorigenesis and progression of prostate cancer. Our planned studies of ncRNAs can contribute major breakthroughs to optimize individualized prostate cancer treatment by providing both novel biomarkers and drug targets. In this project, we will pursue two major clinical problems: 1) early identification of cases requiring aggressive curative treatment, and 2) develop efficient therapies against hormone-refractory prostate cancer. The project will cover all phases of translational research, from discovery to validation and implementation. We will identify novel ncRNAs, investigate their expression, genetic/epigenetic alterations, and function. We will develop diagnostic tools, identify and validate therapeutic targets. To assure the success of the project, our consortium consists of leading translational prostate cancer research centers in Europe and companies committed to develop ncRNA detection technologies and novel drugs.

Keywords: prostate cancer,ncrna,mirna,expression,biomarker,therapy,prognosis,prediction,diagnosis,targeted drugs,genetics,epigenetics,translational