Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Small-molecule Inhibitor Leads Versus emerging and neglected RNA viruses (SILVER)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: France,Germany,Belgium,Netherlands,France,Germany,Netherlands,United Kingdom,Spain,United Kingdom,Austria,Germany,China,Korea, Republic of,Taiwan, Province of China,Italy,Germany,Netherlands,Germany,Switzerland
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-10-01
End date: 2015-03-31
Duration (months): 54.0
Total project cost (EUR): 21899739.32
EU funding (EUR): 12000000.0
Participants: 24
Project status: CLOSED

RNA virus infections kill millions of humans annually, largely due to the lack of suitable vaccines and drugs to control them. This problem is addressed in this FP7 call and in response a consortium of Europe’s and Asia’s leading molecular virologists, structural biologists, medicinal chemists and bioinformaticians has been brought together to generate a state-of-the-art drug discovery and design programme. The project aims to identify Small molecule Inhibitor Leads Versus Emerging and neglected RNA viruses (SILVER). It will focus its activities on selected medically important RNA viruses for which the development of drugs is considered essential (Dengue-, entero- and paramyxoviruses), whereas other relatively neglected and/or emerging RNA viruses will be explored to identify the most promising viral protein targets and antiviral compounds. A pipeline strategy has been developed to enable the inclusion in SILVER of viruses at all levels of existing knowledge. Targets for potential drugs include infectious virus, structurally characterised viral enzymes and other proteins. Leads for currently available antiviral drugs have been identified by screening compound libraries in virus-infected cell culture systems and in vitro assays using purified viral enzymes. Selective inhibitors of viral replication have also been (and are being) derived using detailed structural knowledge of viral proteins and structure-based drug design. Hits will be assayed using individual viral protein targets and replicative proteins in complex with viral RNA. The potential protective activity of the most potent inhibitors, that have a favourable (in vitro) ADME-tox profile, will be assessed in relevant infection models in animals. Licenses on promising compounds or compound classes will be presented to the interested pharmaceutical industry. The SILVER consortium will be well placed to play a major role in contributing to the international effort to develop strategies to improve world health.

Keywords: antiviral drug design,drug discovery,proof of concept
Dissecting the biogenesis of eukaryotic ribosomal subunits (EURIBIO)

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: Switzerland
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-09-01
End date: 2016-07-31
Duration (months): 71.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

In all living cells, the important task of protein synthesis is carried out by the ribosome. A substantial amount of cellular energy and resources is utilized to manufacture ribosomal subunits. In contrast to prokaryotes, eukaryotic ribosome assembly requires a multitude of conserved non-ribosomal trans-acting factors, which transiently associate with pre-ribosomal particles at distinct assembly stages and perform specific maturation steps. Large-scale proteomic approaches in budding yeast, have rapidly expanded the inventory of trans-acting factors (~200). However, little is known regarding their precise site(s) of action and the role(s) of these factors during pre-ribosome assembly. Upon accomplishing their task, majority of the trans-acting factors, are typically released from maturing pre-ribosomes already in the nucleolus/nucleus. Strikingly, a handful of factors remain associated with pre-ribosomes and facilitate their export into the cytoplasm. Release of these factors constitutes “late cytoplasmic maturation events” which render exported pre-ribosomes translation competent. In this proposal we will exploit the powerful model organism budding yeast to: (1) Develop novel biochemical tools to elucidate the molecular environment of trans-acting factors on the surface of pre-ribosomal particles. These analyses will provide us a low-resolution biochemical map of a maturing pre-ribosome. (2) Exploit the powerful combination of genetic and high-throughput visual screening approaches in budding yeast to unravel novel “late cytoplasmic maturation steps” in the 60S biogenesis pathway. Together, my research proposal aims to contribute significantly to our current knowledge regarding the construction and nuclear export of eukaryotic pre-ribosomes. Our analysis will lead us to general principles that underlie the dynamic assembly/dissassembly of large macromolecular ribonucleo-protein complexes.

Keywords: eukaryotic ribosome biogenesis- ribosome export-late cytoplasmic maturation-large subunit maturation
sRNA regulatory networks (MIRNET)

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: United Kingdom
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-11-01
End date: 2015-10-31
Duration (months): 60.0
Total project cost (EUR): 1499999.6
EU funding (EUR): 1499999.6
Participants: 1
Project status: CLOSED

MicroRNAs (miRNAs), a large class of ~22 nucleotide non-coding RNAs (sRNAs) found in many plants and animals act to post-transcriptionally regulate gene expression. Approximately 3% of all known human genes encode miRNAs. Important functions for miRNAs in development, physiology and disease are emerging. Here we propose to identify and characterize miRNA genetic networks by combining forward and reverse genetic approaches, experimental target identification, quantitative cell biology and computational analyses in C. elegans. We will focus our efforts on a set of 14 miRNAs that are conserved between C. elegans and mammals. Specifically, we will test genetic interactions between this panel of miRNA genes and all known genes in C. elegans using synthetic RNAi screens. Based on pilot studies we expect that these screens will identify direct targets of miRNAs as suppressors and genes acting redundantly with miRNA genes as enhancers. In parallel, we will use experimental approaches to identify the direct in vivo targets and upstream transcriptional regulators for these 14 miRNAs. Finally we will use a live assay for miRNA activity to measure the kinetics of the effects of miRNAs on the gene regulatory network. To our knowledge this is the first study to use synthetic genetic screens to uncover genome-wide miRNA regulatory networks. This project is taking advantage of a number of recent advances in C. elegans technology. We will deliver a unique dataset to further our understanding of the biology of individual miRNAs in C. elegans, the characteristics of miRNA regulatory networks in C. elegans and more generally miRNA-dependent control in animals.

Keywords: microrna,mirna,rnai,c. elegans
e-ScienceTalk : Supporting Grid and High Performance Computing reporting across Europe (E-SCIENCETALK)

Framework: FP7 — Capacities
Programme: Research Infrastructures
Destination: Support to policy development and Programme implementation
Action type: Coordination and support actions
Countries involved: Netherlands,United Kingdom,France,Switzerland
Call:  (FP7-INFRASTRUCTURES-2010-2, 2010)
Start date: 2010-09-01
End date: 2013-07-31
Duration (months): 35.0
Total project cost (EUR): 1456245.0
EU funding (EUR): 1300000.0
Participants: 5
Project status: CLOSED

Over the last 10 years, the European Commission and governments have invested substantial funds in scientific grid computing. Scientists have access to state-of-the-art computational and data resources located around the world, putting European research into a leading position to address the greatest challenges facing us today, such as climate change, pandemics and sustainable energy. With the advent of the European Grid Infrastructure and the associated fundamental changes to the way that grid computing will evolve in the future, combined with the blurring of boundaries between grids, clouds, supercomputing networks and volunteer grids, a clear consistent source of information aimed at non-experts is now more important than ever, through dissemination projects that cross national boundaries. e-ScienceTalk will build on the outstanding achievements of the GridTalk project in bringing the success stories of Europe’s e-Infrastructure to policy makers in government and business, to the scientific community and to the general public. E-ScienceTalk will work with the EGI and other collaborating projects to expand the scope of the existing GridTalk outputs, to report on the interactions of grids with e-Infrastructures such as cloud computing and supercomputing, and will also explore options for the sustainability of e-ScienceTalk’s products. e-ScienceTalk will produce a series of reports aimed at policy makers to disseminate key policy issues underpinning grid and e-Infrastructure development in Europe and coordinate e-concertation activities. The GridCafé, GridCast and GridGuide suite of websites will cover new topics and explore novel web technologies, as well as integrating more closely with GridPP’s Real Time Monitor to combine live views of grid activity with the human aspects of computing. The growing weekly publication, International Science Grid This Week (iSGTW) will bring news and events to the existing and potential e-Science community.

Keywords: dissemination,policy,international cooperation,e-infrastructures,grid computing,distributed computing,high performance computing
RNA-mediated virulence gene regulation: Identification of novel antibacterial compounds (RNANTIBIOTICS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Sweden
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-10-01
End date: 2015-09-30
Duration (months): 60.0
Total project cost (EUR): 999996.0
EU funding (EUR): 999996.0
Participants: 1
Project status: CLOSED

All kingdoms possess a large fraction of RNA-based regulation. We identified several small non-coding regulatory RNAs (ncRNAs) in the human bacterial pathogen Listeria monocytogenes that controlled virulence by a direct RNA:RNA interaction. My group have also identified several 5´-untranslated RNAs (5´-UTRs) known to control expression of their downstream mRNA by a switch mechanism triggered by certain metabolites, specific compartments of the host or by different temperatures. In the suggested project, we will analyze the mechanism by how various RNA-species function on a molecular level by biochemical and genetic approaches. By constructing mutations (deletion and base-substitutions), the role of the regulatory RNAs and their targets during pathogenesis will be pin-pointed using different virulence model organisms. For 5´-UTRs binding specific metabolites, we will add non-metabolic analogs to examine if such molecules can block the function of the 5´-UTRs and hence infection. The core structure of one identified ncRNA will be used as a scaffold to develop an RNA interference system in bacteria. At least one RNA-helicase has been shown to be essential for bacterial motility and growth at 4°C. It is being purified to test its in vitro properties at mRNA targets and at different temperatures. Its in vivo role will be analyzed by genetic techniques. Bacterial resistance against different antibiotics is an increasing problem worldwide. We have identified one pyridine molecule specifically targeting listerial virulence gene expression and its mechanism of action will be revealed by genetic and biochemical techniques. A diffusible, although yet unknown molecule, with bacteriostatic activity was observed and its nature and mechanism will be revealed mainly by biochemical experiments. Our work will give important knowledge of how the bacterium uses RNA to sense its surroundings, but will also identifiy new types of antibacterial agents.

Keywords: rna-regulation,ncrnas,srnas,5'-untranslated rna,listeria,virulence,novel antibiotics,antibacterial agents,virulence inhibition,blue-light receptor
The impact of Regulation (EC) No 1394/2007 on the development of Advanced Therapy Medicinal Products (ATMPs): an academic perspective (ACADEMIC GMP)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Coordination and support actions
Countries involved: Germany,Sweden,United Kingdom,Austria,United Kingdom,Germany,Germany,Germany
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-09-01
End date: 2013-05-31
Duration (months): 33.0
Total project cost (EUR): 557520.0
EU funding (EUR): 498747.0
Participants: 9
Project status: CLOSED

Advanced Therapy Medicinal Products (ATMPs) are medicinal products for human use, based on gene therapy, somatic cell therapy or tissue engineering. A rapidly growing area in translational research, they represent the ‘next generation’ of complex medicines for complex diseases and pose particular challenges to medicines regulation. Regulation (EC) No 1394/2007 has been designed to ensure the free movement of ATMPs within the European Union (EU), to facilitate their access to the EU market and to foster the competitiveness of European pharmaceutical companies while guaranteeing the highest level of health protection for patients. The regulation extends standards of current Good Manufacturing Practice (cGMP) to ATMPs to ensure their quality, safety and efficacy. Academic cGMP facilities are major contributors to the development of ATMPs. They respond to clinical needs and provide medicinal products in an environment which, albeit compliant with industrial standards, is by definition not industrial. They find themselves in a challenging position between various, sometimes conflicting interests in the transition of ATMPs from bench to bedside. European investigator-initiated multicenter trials on ATMPs critically depend on academic cGMP facilities. We will assess the impact of Regulation (EC) No 1394/2007 on academic cGMP facilities by: a) conducting a European survey among non-industry facilities in this sector; b) organising workshops and a major conference for targeted, collaborative discourse; c) establishing a web-based platform for information exchange; d) analysing publications and guidance from the perspective of better regulation principles; e) analysing innovation statistics in relation to ATMPs. These activities will yield comprehensive evidence and concrete suggestions to policy makers. The project will in itself foster a dialogue that will strengthen networks of translational research and thus contribute to research excellence in Europe.

Keywords: current good manufacturing practice (cgmp),advanced therapy medicinal products (atmp),academic cgmp facilities
Dissecting a minimal genome: a physical investigation of DNA transactions in mitochondria (PHYSGENE)

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: Netherlands
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2015-12-31
Duration (months): 60.0
Total project cost (EUR): 1497868.0
EU funding (EUR): 1497868.0
Participants: 2
Project status: CLOSED

I propose to unravel parts of the mechanochemistry of two key genome transactions: replication and transcription using an array of single-molecule techniques. To this end, I propose to study the minimal genomic machinery of mitochondria. Mitochondria are organelles in eukaryotic cells that contain their own DNA (mtDNA). Significant understanding of the biochemistry of DNA transactions in mitochondria is obtained from the in vitro reconstitution of mitochondrial replication and transcription. However, elucidating the physics of these molecular mechanisms has only just started. A major challenge of the coming decades will be dissecting and quantifying biological systems to such an extent that it makes predictive modeling possible. Single-molecule tools play a major role in this development. Hence, I plan within the scope of this proposal, to combine optical manipulation with powerful fluorescent techniques. This combination of single-molecule manipulation and fluorescence has much more potential than has been explored, so far. With the development of such tools complex biological systems can not only be controlled and measured but also visualized at the same time. The human mitochondrial genetic machinery is an ideal system for such an approach, because replication and transcription can be re-created in vitro with only seven proteins. Hence, this proposal represents a unique opportunity to quantitatively dissect a genetic machine that is actually accessible by biophysical tools. Finally, about 1 in 5000 humans suffers from a disease caused by mutations of in the mtDNA. The research proposed here will permit direct observation of proteins in action. Normal and dysfunctional proteins can thus be compared, permitting insight in the mechanistic basis of a disorder.

Keywords: single-molecule biophysics,optical tweezers,mitochondria,dna-protein machinery
Treat Infections in NeoNates 2 - Evaluation of an infective agent (azithromycin) for the treatment of infections in preterm and term neonates (TINN2)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Collaborative project
Countries involved: France,United Kingdom,United Kingdom,United Kingdom,Netherlands,Germany,Italy,Luxembourg,Germany,Sweden,Belgium,Hungary
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2011-01-01
End date: 2015-12-31
Duration (months): 60.0
Total project cost (EUR): 6540008.8
EU funding (EUR): 5000000.0
Participants: 16
Project status: CLOSED

The aim of TINN2 is to evaluate azithromycin, included in the EMEA priority list of the therapeutic areas that need specific drug evaluation in preterm and term neonates. Azithromycin is a macrolid antibiotic with anti-inflammatory properties active against Ureaplasma. It might be effective in reducing the severity of bronhopulmonary disease in which Ureaplasma infection and inflammation play a role. TINN2 involves European leaders in neonatology, paediatric pharmacology, methodology and SMEs that will establish links with ethical bodies and regulatory authorities. The programme will perform in silico experiments and evaluate formulations for neonates. The randomized placebo-controlled trial will be optimized using age-appropriate state-of-the-art methods adapted to neonates (including in silico experiments, pharmacokinetics and pharmacogenetics) to validate the components of a Paediatric Investigation Plan. It will be performed by neonatologists trained in paediatric pharmacology and clinical research in line with guidelines on Good Clinical Practice. All the ethical issues will be considered, including pain and distress, blood sampling (number and volume) and informed consent. Parent information sheets and consent form will be submitted to parents’ associations for approval. TINN2 will include short term safety and potential for long term adverse reactions. Results will be reported in order to allow a PUMA application and to improve neonatal care. Therefore, TINN2 will validate the appropriate use of azithromycin in neonates which will be of direct benefit to children, their families and health professionals. TINN2 will strengthen paediatric drug evaluation across Europe, support recent initiatives from the European pharmaceutical industry and build up a network of units with experience in clinical research that will be used for additional drug evaluation in neonates.

Keywords: paediatrics,azithromycin,emea list,puma,pip,clinical trial,preterm and term neonates,pharmacokinetics,pharmacogenetics
Modulation of synaptic plasticity and circuit function by regulation of neurotrophin exocytosis (SYT ACTIVITY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: ERC Starting Grant Interdisciplinary Panel
Countries involved: Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-04-01
End date: 2016-03-31
Duration (months): 60.0
Total project cost (EUR): 1484000.0
EU funding (EUR): 1484000.0
Participants: 1
Project status: CLOSED

A fundamental question in neuroscience is how individual synapses and neurons act in concert to create functional circuits. While the basic mechanisms of synaptic transmission between neurons are well understood, much less is known about how individual synapses, neurons, and circuits dynamically adjust their transmission properties in response to perturbations in network activity. During the past few years I have begun a new line of research: the regulation of neurotrophin vesicle release and its effect on synaptic plasticity and learning and memory. These discoveries come at a crucial time, given mounting evidence that BDNF and other neurotrophins and neuropeptides affect synaptic plasticity, while at the same virtually nothing is known about the regulation of their release and the mechanisms by which they affect synapse and circuit function. To continue this research I would like to form my own research group. I am interested in the mechanisms by which individual synapses and neurons respond to changes in activity to modify circuit function and ultimately behavior. I investigate the mechanisms of activity-dependent plasticity at three different levels: single synapses, single cells and neuronal networks, using a combination of manipulation of protein expression and function, biochemistry, electrophysiology and live imaging approaches in neuron cultures and brain slices. My overall goal is to understand how neurons communicate changes in activity to affect circuit function.

Keywords: molecular & cellular neuroscience,synaptic transmission & plasticity,neurotrophins,exocytosis