Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
ALK as a common target for the pathogenesis and therapy in lymphoma, lung carcinoma and neuroblastoma (LUNELY)

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: Italy
Call:  (ERC-2009-StG, 2009)
Start date: 2009-11-01
End date: 2014-04-30
Duration (months): 54.0
Total project cost (EUR): 1010000.0
EU funding (EUR): 1010000.0
Participants: 1
Project status: CLOSED

The Anaplastic Lymphoma Kinase (ALK) has been discovered as the result of chromosomal translocations in Anaplastic Large Cell Lymphomas (ALCL) (Chiarle et al Nat Rev Cancer. 2008, 8:11). In ALCL, the role of the ALK oncogenic translocations has been established in vitro and in transgenic mouse models. Recent findings have shown ALK translocations, mutations or amplifications in other types of solid cancers, such as lung carcinoma (Soda et al. Nature. 2007, 448:561) and neuroblastoma (Mossè et al. Nature 2008, 455: 930). However, the role of ALK gene mutations in these solid tumours remains largely undetermined. This lack of knowledge is even worse given the fact that a therapy that targets ALK in these tumours could be feasible. Aim 1. Targeting of ALK in ALCL lymphomas. ALCL ALK positive lymphomas will be tested for small molecule inhibitors of the activity of ALK. In addition, a combination of gene silencing, such as small interfering RNA (siRNA), and vaccination against ALK will be validated as selective ALK therapies. Aim 2. Characterization of the role of ALK in lung cancer through the generation of mouse models. We propose to characterize the pathogenetic role of ALK in lung cancer by in vitro studies and by generating mouse models for ALK positive lung cancers. These mouse models will be fundamental to validate the innovative therapies against ALK positive lung carcinoma. Aim 3. Validation of ALK as an oncogene and a therapeutic target in neuroblastoma. We plan to develop mouse models of neuroblastoma to investigate the pathogenetic role of ALK in the onset and maintenance of neuroblastoma in vivo. These mouse model of neuroblastoma will be used for the validation of ALK specific therapies. Overall, the proposed project will define the role of ALK in lymphoma, neuroblastoma and lungcancer and validate its potential use as a a target for therapy in those tumours. The impact of these novel therapies will be of great value in these deadly tumours.

Keywords: lymphoma,neuroblastoma,lung cancer,kinase inhibitors,vaccination,mouse models
MECHANISMS UNDERLYING CELL FATE DECISION BETWEEN PANCREAS AND LIVER (HEPATOPANCREATIC)

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: Germany
Call:  (ERC-2009-StG, 2009)
Start date: 2009-11-01
End date: 2014-10-31
Duration (months): 60.0
Total project cost (EUR): 1186745.97
EU funding (EUR): 1186745.97
Participants: 1
Project status: CLOSED

Diabetes is a degenerative disease affecting millions of persons worldwide. A cure for diabetes depends on replacing the insulin-producing ²-cells in the pancreas that are destroyed by the disease. An attractive strategy to attain this goal is to convert liver adult cells of the same patient into pancreatic ²-cells. The liver and pancreas share many aspects of their early development and are specified in adjacent regions of the endoderm, possibly from a common bipotent progenitor cell. Therefore, conversion of liver to pancreas is conceivable and should imply only few steps backward to a common progenitor and little epigenetic changes. However, how pancreatic versus hepatic fate decision occurs during development is still poorly understood. The aim of this proposal is two fold: to perform lineage analysis, and to study developmental regulators of pancreatic versus hepatic fate decision. We will use new genetic tools, based on the GFP and photoconvertible Kaede fluorescent proteins, to address: i. if the liver and pancreas arise from a common bipotent progenitor cell; ii. to trace in vivo; and iii. molecularly profile the presumptive precursor cell and its descendants in the mouse embryo. Our previous studies have identified target genes of the GATA factors that might act as intrinsic developmental regulators of the pancreatic versus hepatic fate decision. Both intrinsic factors together with extrinsic regulators, such as BMP, will be studied. We will test their potential to promote lineage reprogramming of liver to pancreas using the mouse as well as mouse embryonic stem cells as model systems. Understanding how distinct cell types arise from common multipotent progenitor cells is a major quest in developmental biology. Our findings will elucidate the spatiotemporal mechanisms that control pancreas versus liver fate decision. In addition, they will provide the blueprint for lineage reprogramming of adult hepatic cells to pancreas in diabetes cell-therapy.

Keywords: beta-cells,diabetes,liver,pancreas,endoderm,stem cells
Cytosolic recognition of foreign nucleic acids: Molecular and functional characterization of AIM2, a central player in DNA-triggered inflammasome activation (AIM2 INFLAMMASOME)

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: Germany
Call:  (ERC-2009-StG, 2009)
Start date: 2009-12-01
End date: 2014-11-30
Duration (months): 60.0
Total project cost (EUR): 1727920.0
EU funding (EUR): 1727920.0
Participants: 1
Project status: CLOSED

Host cytokines, chemokines and type I IFNs are critical effectors of the innate immune response to viral and bacterial pathogens. Several classes of germ-line encoded pattern recognition receptors have been identified, which sense non-self nucleic acids and trigger these responses. Recently NLRP-3, a member of the NOD-like receptor (NLR) family, has been shown to sense endogenous danger signals, environmental insults and the DNA viruses adenovirus and HSV. Activation of NLRP-3 induces the formation of a large multiprotein complex in cells termed inflammasome , which controls the activity of pro-caspase-1 and the maturation of pro-IL-1² and pro-IL18 into their active forms. NLRP-3, however, does not regulate these responses to double stranded cytosolic DNA. We identified the cytosolic protein AIM2 as the missing receptor for cytosolic DNA. AIM2 contains a HIN200 domain, which binds to DNA and a pyrin domain, which associates with the adapter molecule ASC to activate both NF-ºB and caspase-1. Knock down of AIM2 down-regulates caspase-1-mediated IL-1² responses following DNA stimulation or vaccinia virus infection. Collectively, these observations demonstrate that AIM2 forms an inflammasome with the DNA ligand and ASC to activate caspase-1. Our underlying hypothesis for this proposal is that AIM2 plays a central role in host-defence to cytosolic microbial pathogens and also in DNA-triggered autoimmunity. The goals of this research proposal are to further characterize the DNA ligand for AIM2, to explore the molecular mechanisms of AIM2 activation, to define the contribution of AIM2 to host-defence against viral and bacterial pathogens and to assess its function in nucleic acid triggered autoimmune disease. The characterization of AIM2 and its role in innate immunity could open new avenues in the advancement of immunotherapy and treatment of autoimmune disease.

Keywords: macrophages,dendritic cells,caspase-1,interleukin-1
A study on the interaction among natural selection, mutation and recombination, with Caenorhabditis elegans experimental evolution (EXPTEVOLCELEGANS)

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,Portugal
Call:  (ERC-2009-StG, 2009)
Start date: 2010-02-01
End date: 2016-01-31
Duration (months): 72.0
Total project cost (EUR): 1694000.0
EU funding (EUR): 1694000.0
Participants: 2
Project status: CLOSED

The process of adaptation to novel environments is of extraordinary importance to understand the existence of biological diversity. The development of a theory of adaptation during the last 150 years identified natural selection as its cause, and the conditions under which it depends on the existence of the heritable variation encoded in DNA sequences, introduced in finite populations by mutation, recombination and migration. Despite the considerable knowledge about the mechanism of evolution, an understanding of genetic basis of adaptation remains both a theoretical and an empirical challenge. In this project we propose to conduct an unprecedented large scale evolution experiment with the androdioecious nematode Caenorhabditis elegans, under varying levels of outcrossing rates, initial standing genetic variation and frequency of environmental change. With the integration of information from several levels of structural organization, from fitness-proxy and life-history phenotypes to genome wide RNA expression, it will be possible to determine the several genetic and environmental components of diversity. Furthermore, we will perform whole genome linkage disequilibrium (LD) association mapping with experimental evolution, thus determining at the DNA sequence level how the genome is organized and how it feeds back into the population genetic dynamics. Tests of evolutionary theory will be conducted with the data collected. Directional natural selection is expected to maintain genotype diversity, when there are non-linear interactions among several loci. But predominantly stabilizing selection will erode this genetic diversity. While in the first scenario outcrossing will be favoured, in the second it will be a hindrance to adaptation. After an initial characterization, we will work with ~90 populations and measure &gt;104 phenotypes. For mapping we will assay an estimated 106 genotypes. Most of the analytical tools have already been developed.

Keywords: experimental evolution,c. elegans,ld association mapping,rna expression,life-history
Immune mechanisms of osteopontin-mediated protection in allergic airway disease (OPN-IMMUNOREGULATION)

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: Greece
Call:  (ERC-2009-StG, 2009)
Start date: 2009-12-01
End date: 2015-11-30
Duration (months): 72.0
Total project cost (EUR): 1511200.0
EU funding (EUR): 1511200.0
Participants: 1
Project status: CLOSED

In allergic asthma, an important health problem, disease is driven by allergen-specific Th2 immune responses. Differentiation of Th2 cells depends on their early interactions with antigen presenting cells, such as dendritic cells (DCs), and cytokines are crucial for this process. Osteopontin (Opn) was originally identified as an important cytokine for Th1 immunity and autoimmunity. Our group recently demonstrated that Opn is highly expressed in the lungs of asthmatic patients and of mice with Th2-mediated allergic airway inflammation. Our work revealed anti-allergic effects of Opn on airway disease during secondary pulmonary antigenic challenge mediated by regulation of DC subsets. In addition, intranasal administration of recombinant Opn during pulmonary exposure to the allergen protected mice from allergic airway disease suppressing all features of disease, recruitment of Th2 cells and allergen-specific Th2 responses. Our previous experiments, as well as preliminary studies presented in this proposal, point to an important novel immunoregulatory role for Opn in the Th2 setting. However, most aspects of the Opn-mediated immune mechanism of protection remain unclear. With this proposal, we aim at elucidating the immunoregulatory/protective mechanisms of Opn utilizing immunologic, molecular and genomic approaches as well as in vivo mouse models of allergic airway inflammation. We propose to investigate the mechanisms mediating Opn-effects on: (1) DC subsets and Treg cells that confer protection during pulmonary allergen challenge (2) recruitment and function of allergen-specific Th2 (generated during sensitization) as well as of newly-activated Th effector cells and their interactions during pulmonary allergen challenge and (3) antigenic tolerance induction in the Th2 setting. The studies proposed here will provide new insight into the biology of Opn-dependent regulation of DC subsets, Th2 responses and DC-T cell interactions opening new important questions in im

Keywords: cytokines,osteopontin,th2,plasmacytoid dendritic cells,conventional dendritic cells,t helper cells,t regulatory cells,allergic airway inflammation
Transport related Air Pollution and Health impacts – Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM)

Framework: FP7 — Cooperation
Programme: Environment (including Climate Change)
Destination: Climate change, pollution, and risks
Action type: Collaborative project
Countries involved: United Kingdom,Netherlands,Netherlands,Norway,Finland,Germany,Belgium,Greece,European organisations area,United Kingdom,Sweden,Germany,Denmark,United Kingdom,Switzerland,Lithuania,Germany,Czechia
Call:  (FP7-ENV-2009-1, 2009)
Start date: 2010-01-01
End date: 2014-06-30
Duration (months): 54.0
Total project cost (EUR): 9227610.28
EU funding (EUR): 6915553.92
Participants: 21
Project status: CLOSED

TRANSPHORM brings together leading air quality and health researchers and users to improve the knowledge of transport related airborne particulate matter (PM) and its impact on human health and to develop and implement assessment tools for scales ranging from city to Europe. Over four years, TRANSPHORM will aim to develop and implement an integrated methodology to assess the health impacts of PM air pollution covering the whole chain from emissions to disease burden. The objectives will be: (i) To improve our understanding of transport sources of size-resolved and speciated PM air pollution including non-exhaust, shipping, aviation and railways; (ii) To improved emission factors of ultrafine particle number (PN0.1) and mass fractions of PM1, PM2.5 and PM10 for key transport sources; (iii) To conduct targeted measurements in Rotterdam, Helsinki and Thessaloniki for source apportionment, exposure assessment and model evaluation; (iv) To quantify exposure to airborne PM in urban environments resulting from traffic, road, shipping, rail and aviation; (v) To improve and integrate air quality dispersion and exposure models for urban and regional scales including long-range transport; (vi) To develop new concentration-response (CRF) linking long and short-term ambient residential exposure to size-resolved and speciated PM with key health endpoints; (vii) To develop and implement integrated assessment tool to investigate and analyse the whole chain of processes for selected cities and Europe; (viii) To incorporate micro-environmental PM concentrations, time-activity patterns, and estimates of internal dose into the health impact assessment; (ix) To conduct integrated health assessment of selected European cities; (x) To design and implement mitigation and adaptation strategies for European and international policy refinement and development; (xi) To exploit the results of TRANSPHORM through global dissemination and interactions with stakeholders.

Keywords: transport,air pollution,particulate matter,health impacts,integrated assessment,full chain,exposure,modelling,concentration-response functions,ultrafine,pm1,pm2.5,pm10,particle number
Developing novel intelligent labels for chilled and frozen food products, promoting the influence of smart labels application on waste reduction, food quality and safety in the European supply chains (IQ-FRESHLABEL)

Framework: FP7 — Capacities
Programme: Research for the benefit of SMEs
Destination: Research for SME associations
Action type: Research for the benefit of specific groups
Countries involved: Germany,Finland,Germany,Greece,Germany,France,Romania,Poland,Norway,Israel,Sweden,Germany
Call:  (FP7-SME-2008-2, 2008)
Start date: 2010-08-01
End date: 2014-01-31
Duration (months): 42.0
Total project cost (EUR): 2481595.69
EU funding (EUR): 1857470.0
Participants: 18
Project status: CLOSED

IQ-FRESHLABEL will develop two novel innovative intelligent labels. One will monitor the time and temperature of frozen products, the other also the oxygen content in modified atmosphere packed fresh food. Controlling post production life cycle of food is important element of food supply chain. Improper handling of product during transport, storage and in households results in quality defects, increases risk of microbial growth, subsequent spoilage and edible waste of food. The FRESHLABEL project succeeded in development of the first generation of commercially available and applied Time-Temperature-Indicators (TTIs) for fresh products. FESHLABEL demonstrated that number of rejected products and, thus, economical losses within a supply chain can be considerably reduced. However, the project showed that there are still many unexploited application areas for smart labels, which IQ-FRESHLABEL will reduce by the development of novel intelligent labels for the packaging of meat and fish products. IQ-FRESHLABEL will develop TTIs for the application on frozen fish products. These TTIs have to meet different demands compared to the TTIs for fresh products. Storage time is much longer and the temperature difference between optimal storage and risky high temperatures is much higher, but quality deterioration occurs already at slightly increased temperatures. Furthermore, IQ-FRESHLABEL will develop intelligent labels for modified atmosphere packaged (MAP) fresh poultry meat. These labels will show a colour change when the modified atmosphere, which has most cases a high level of carbon dioxide and a low level of oxygen is changing. This can happen when packages are damaged. Next to the research on novel intelligent labels, IQ-FRESHLABEL will conduct consumer and retailer behaviour study with respect to intelligent labels application in order to support design of novel TTIs in a unique approach. Cost benefit analysis will be conducted to estimate cost of smart labels application.

Keywords: inteligent packaging,smart labels,tti,oxygen indicator,critical temperature indicator
New manufacturing infrastructure for the production of high quality Natural Fibres (ULTRAFIBRE)

Framework: FP7 — Capacities
Programme: Research for the benefit of SMEs
Destination: Research for SME associations
Action type: Research for the benefit of specific groups
Countries involved: Italy,France,United Kingdom,Netherlands,Germany,United Kingdom,Poland,Türkiye,United Kingdom,Italy,United Kingdom
Call:  (FP7-SME-2008-2, 2008)
Start date: 2010-01-01
End date: 2012-12-31
Duration (months): 36.0
Total project cost (EUR): 2228313.0
EU funding (EUR): 1742245.0
Participants: 14
Project status: CLOSED

Natural fibres offer a route to the production of sustainable composites, replacing inorganic and petrochemical based fibres with high-embodied energy. One of the main obstacles to the exploitation of natural fibres is the limited consistency of supply, with batch-to-batch variations in quality. Retting – a process whereby plant stems are left to weather in the fields – has been identified as being the weak point in fibre processing in the as a result of variable weather conditions during the retting period. Mechanical decortication – the removal of the outer layers – is often damaging to the fibres. UltraFibre will develop a clean processing technology called ‘hydroacoutstic decorticaton’ to extract the fibre from the plant after harvesting avoiding reliance on degree of dew retting. The fibre produced will be of much higher quality, without the physical damage caused by mechanical decortication, circumventing reliance on unpredictable weather for completion of dew retting in fields. Chemical treatments have been used to modify fibres to improve matrix to fibre adhesion in composite materials. However, these chemical treatments use hazardous materials, are time-consuming and create a significant level of waste. Therefore, a treatment process that does not pose a threat to the natural environment and that is reproducible, whilst creating little or no hazardous waste, would be extremely advantageous. To achieve this end, UltraFibre will develop a ‘soft plasma’ treatment process that will integrate with the hydroacoustic decortication process to produce high quality fibre for the rapidly expanding composites materials sector.

Keywords: natural fibres,composites,polymer processing,clean technology,ultrasonics
A Platform Power Management System and Low Voltage Drive Train for Hybrid and Electric Vehicles (SAFEDRIVE)

Framework: FP7 — Capacities
Programme: Research for the benefit of SMEs
Destination: Research for SME associations
Action type: Research for the benefit of specific groups
Countries involved: France,France,Belgium,United Kingdom,Croatia,Switzerland,United Kingdom,Spain,United Kingdom,United Kingdom,Czechia,United Kingdom
Call:  (FP7-SME-2008-2, 2008)
Start date: 2010-08-01
End date: 2013-12-31
Duration (months): 41.0
Total project cost (EUR): 3083088.4
EU funding (EUR): 2294422.66
Participants: 14
Project status: CLOSED

The European hybrid, electric and fuel cell vehicle industry represents 1,600 SME manufacturers and suppliers. They commercialise small volumes of low-emission vehicles, including taxis, delivery vans, factory vehicles and domestic cars. However with current technologies their market is limited and their development has been split between low-cost mass market and expensive high-performance vehicles. These vehicles do not meet customer performance demands, at a price point which is competitive with IC engines. Large vehicle manufacturers overcome this gap and reduce their development costs by platform sharing component technologies. However due to the lack of collaboration within our industry, this platform technology is not available. This proposal addresses this technology gap though the development of an open platform power management system, with customisable performance and efficiency. The platform will be supported by a modular platform drive motor topology, based on a fully scalable axial flux design (100Nm to 1,200Nm cont. torque). The low cost technology will be sufficiently high torque to drive the wheels at a high speed, without requiring an intermediate gearbox. To further drive down cost we will use the housing of the liquid cooled drive motor, as a heat sink for a high current power convertor. This will be achieved by applying a circuit board directly onto the motor housing, using a thermal spraying technology. The project will benefit Europe through increased sales of low-emission vehicles and enable our members to reduce development time by 20% and component cost by 40%. The modular drive motor platform will enable our members to manufacturer desirable vehicles at a competitive price and reduce the total vehicle cost by up to 13%. In addition we will offset imports by EU manufacturing of new drive motors, increasing European revenues by €257 million and profits by €51 million.

Keywords: platform power management drive motor