Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Transporter pharmacogenomics – the contribution of transporters to variability in drug response (TRANSPORTERPGX)

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: Finland
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1882212.0
EU funding (EUR): 1882212.0
Participants: 1
Project status: CLOSED

The response to drug therapy varies widely between individuals. Proteins involved in the absorption, distribution, metabolism and excretion of drugs play a central role in determining the concentration of a drug at the target site, and thus drug efficacy and toxicity. Transporters are membrane proteins that mediate the translocation of chemicals into and out of cells using active and passive mechanisms. We have identified a single nucleotide variant in the SLCO1B1 gene encoding the organic anion transporting polypeptide 1B1 (OATP1B1), which severely impairs the hepatic uptake of the cholesterol-lowering drug simvastatin leading to an increased systemic exposure to the drug, and a markedly increased risk of simvastatin-induced muscle toxicity. The effects of this variant differ significantly between statins, forming a rational basis for individualized lipid-lowering therapy. In addition to OATP1B1, also OATP1A2, OATP1B3, and OATP2B1 are known to transport several drugs in vitro (e.g., anticancer, cardiovascular and anti-infective drugs). However, the roles of these transporters in the pharmacokinetics of drugs in vivo in humans are unknown. The aim of this project is to systematically search for genetic variants of SLCO1A2, SLCO1B3 and SLCO2B1, which have functional significance in vivo in humans. This project will enable studies to determine the roles of these transporters in the pharmacokinetics of drugs and in the disposition of endogenous compounds in vivo, with implications for drug development and drug safety. Moreover, functionally significant variants in these genes may be used to personalize drug therapies. Overall, the project can significantly facilitate the development of new drugs and can improve the safe and effective use of drugs already in clinical use, thus increasing the health and well-being of mankind and reducing the overall costs of healthcare and drug development.

Keywords: transporter,pharmacokinetics,organic anion transporting polypeptide,oatp1a2,oatp1b3,oatp2b1,slco1a2,slco1b3,slco2b1
NOVEL STRATEGIES FOR BRAIN REGENERATION (BRAINGAIN)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Sweden
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

In contrast to mammals, newts possess exceptional capacities among vertebrates to rebuild complex structures, such as the brain. Our goal is to bridge the gap in the regenerative outcomes between newts and mammals. My group has made significant contributions towards this goal. We created a novel experimental system, which recapitulates central features of Parkinson’s disease in newts, and provides a unique model for understanding regeneration in the adult midbrain. We showed an unexpected but key feature of the newt brain that it is akin to the mammalian brain in terms of the extent of homeostatic cell turn over, but distinct in terms of its injury response, showing the regenerative capacity of the adult vertebrate brain by activating neurogenesis in normally quiescent regions. Further we established a critical role for the neurotransmitter dopamine in controlling quiescence in the midbrain, thereby preventing neurogenesis during homeostasis and terminating neurogenesis once the correct number of neurons has been produced during regeneration. Here we aim to identify key molecular pathways that regulate adult neurogenesis, to define lineage relationships between neuronal stem and progenitor cells, and to identify essential differences between newts and mammals. We will combine pharmacological modulation of neurotransmitter signaling with extensive cellular fate mapping approaches, and molecular manipulations. Ultimately we will test hypotheses derived from newt studies with mammalian systems including newt/mouse cross species complementation approaches. We expect that our findings will provide new regenerative strategies, and reveal fundamental aspects of cell fate determination, tissue growth, and tissue maintenance in normal and pathological conditions.

Keywords: regeneration,salamander,newt,neurogenesis,homeostasis,plasticity,fate mapping,brain,neurodegeneration
Regulation of neuronal connectivity and plasticity by activity-dependent mitochondrial trafficking to synapses (FUELLINGSYNAPSES)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: United Kingdom
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2018-01-31
Duration (months): 72.0
Total project cost (EUR): 1997567.0
EU funding (EUR): 1997567.0
Participants: 1
Project status: CLOSED

Regulated trafficking of mitochondria is essential for providing ATP at the correct spatial location to power neural computation, and for providing calcium buffering at sites of calcium entry or release. In neurons, the concentration of mitochondria in specific regions such as growth cones and synapses is important for correct neuronal function and development. Moreover mutations in proteins regulating mitochondrial trafficking compromise neuronal development and the formation, function and plasticity of synapses, and defective mitochondrial trafficking is increasingly implicated in neurological diseases. Understanding the molecular mechanisms that allow neurons to tailor the distribution of mitochondria to changes in neuronal activity therefore has important implications for our understanding of neuronal function and communication. This proposal will study the mechanisms that control the trafficking of the energy providing mitochondria within neurons, and how this relates to neuronal connectivity and plasticity. Using imaging, electrophysiological, molecular and cell biological techniques, combined with viral transduction and mouse transgenic approaches we will determine the molecular mechanisms underlying the activity-dependent subcellular positioning of mitochondria in neurons. We will examine how the mitochondrial Ca2+-sensing GTPases Miro1 and Miro2 act to regulate mitochondrial movement, distribution and function and how this contributes to neuronal development, synaptogenesis and synaptic plasticity. A key goal will be to determine if different roles exist for constitutive versus activity-dependent control of mitochondrial transport by Miro1 and Miro2 in these processes. These studies will significantly advance our understanding of the molecular mechanisms that control mitochondrial localisation in neurons and the role that activity-dependent mitochondrial trafficking plays in regulating neuronal development, morphogenesis, connectivity and function.

Keywords: mitochondria,synapse,motor protein,plasticity,organelle,trafficking,transport,cytoskeleton
A BLUEPRINT of Haematopoietic Epigenomes (BLUEPRINT)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Netherlands,United Kingdom,United Kingdom,Switzerland,Germany,Spain,Italy,Germany,Spain,Germany,Germany,Italy,Belgium,United Kingdom,France,Israel,Netherlands,Germany,United Kingdom,Sweden,Denmark,Netherlands,Germany,Germany,Sweden,Germany,Austria,Germany,Sweden
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2016-09-30
Duration (months): 60.0
Total project cost (EUR): 39664716.88
EU funding (EUR): 29996664.0
Participants: 45
Project status: CLOSED

In response to the call for a high impact initiative on the human epigenome, the BLUEPRINT Consortium has been formed with the aim of generating at least 100 reference epigenomes and studying them to advance and exploit knowledge of the underlying biological processes and mechanisms in health and disease. BLUEPRINT will focus on distinct types of haematopoietic cells from healthy individuals and on their malignant leukaemic counterparts. Reference epigenomes will be generated by state-of-the-art technologies from highly purified cells for a comprehensive set of epigenetic marks in accordance with quality standards set by IHEC. This resource-generating activity will be conducted at dedicated centres to be complemented by confederated hypothesis-driven research into blood-based diseases, including common leukaemias and autoimmune disease (T1D), by epigenetic targets and compound identification, and by discovery and validation of epigenetic markers for diagnostic use. By focussing on 100 samples of known genetic variation BLUEPRINT will complete an epigenome-wide association study, maximizing the biomedical relevance of the reference epigenomes. Key to the success of BLUEPRINT will be the integration with other data sources (i.e. ICGC, 1000 genomes and ENCODE), comprehensive bioinformatic analysis, and user-friendly dissemination to the wider scientific community. The involvement of innovative companies will energize epigenomic research in the private sector by creating new targets for compounds and the development of smart technologies for better diagnostic tests. BLUEPRINT will outreach through a network of associated members and form critical alliances with leading networks in genomics and epigenomics within Europe and worldwide. Through its interdisciplinarity and scientific excellence combined with its strong commitment to networking, training and communication BLUEPRINT strives to become the cornerstone of the EU contribution to IHEC.

Keywords: reference epigenome,haematopoiesis,leukaemia,type 1 diabetes,dna (hydroxy)methylation,epi-targets,biomarkers,compounds screening,genome-epigenome variation,training,outreach,mouse models
Safety Evaluation of Adverse Reactions in Diabetes (SAFEGUARD)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Collaborative project
Countries involved: Netherlands,Spain,United Kingdom,Spain,Italy,Czechia,Netherlands,United States,Italy,Germany,Netherlands,United Kingdom
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2015-09-30
Duration (months): 48.0
Total project cost (EUR): 3881341.0
EU funding (EUR): 2997196.0
Participants: 17
Project status: CLOSED

In 2010 a widely marketed drug for the treatment of type 2 diabetes (T2DM) (rosiglitazone) was taken from the market as it was associated with an increased risk of myocardial infarction, a T2DM complication it was actually supposed to prevent. This example shows several things. First, the approval requirements do not guarantee a longer term positive benefit risk profile. Second, large scale postmarketing studies are desperately needed to monitor the benefit risk profile throughout the lifecycle of T2DM drugs, and to achieve the required scale collaboration across countries is mandatory. Many novel T2DM drugs have come to the market, all on the basis of the same surrogate endpoints. New safety issues are constantly arising, such as potential associations with pancreatitis, pancreas cancer, bladder cancer, acute renal failure, etc. In the SAFEGUARD Consortium we have assembled an excellent multidisciplinary group of experts who collaboratively aim to quantify the cardiovascular, cerebrovascular and pancreatic safety risk of the T2DM drugs, in particular the more novel drugs by investigating 1) published clinical trials and observational studies; 2) spontaneously reported adverse event reports in national and international pharmacovigilance databases; 3) data from nine population-based health care databases in six countries capturing longitudinal drug exposure and event data on more than 1.7 million T2DM patients. Data elaboration will be distributed but standardized through common protocols, data models and scripts. To put the epidemiological results into perspective, intensive monitoring mechanistic studies in human will be conducted to further understand how and why these T2DM drugs may affect the cardiovascular, digestive or renal system. The SAFEGUARD consortium will yield a harmonized epidemiological data platform on a large T2DM population, which could easily be used to address newly occurring safety issues in the future.

Keywords: type 2 diabetes,safety,cardiovascular,pancreas,renal,mechanisms,decision model
Dobutamine for NEOnatal CIRCulatory failure defined by novel biomarkers (NEO-CIRC)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Collaborative project
Countries involved: United Kingdom,France,Germany,Spain,Germany,United Kingdom,Germany,Spain,Romania,Hungary,Hungary,Türkiye,United States,Romania,United Kingdom,Spain
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2018-09-30
Duration (months): 84.0
Total project cost (EUR): 7788724.86
EU funding (EUR): 5999167.55
Participants: 19
Project status: CLOSED

Dobutamine and adrenaline are widely used as second line therapy for systemic hypotension in infants. Dopamine is currently the most widely used first line drug. In neonates, sustained hypotension may, and impaired organ perfusion will, cause brain injury and poor neurodevelopmental outcomes. All three catecholamines are currently used off-label and have different modes of action which may result in potentially harmful haemodynamic effects. No reliable safety or efficacy data exists for the use of these drugs in neonates or newborns. Furthermore, no uniform criteria exist to define hypotension and there is little evidence to support current intervention strategies, which vary widely. Recently, superior vena cava (SVC) flow has been proposed as a more reliable indicator of circulatory failure than low blood pressure and preliminary results suggest Dobutamine is the optimum therapeutic in such cases. NEO-CIRC proposes 1) a randomised placebo controlled trial to provide safety and efficacy data for Dobutamine as a first line inotrope for all gestational ages 2) to perform pre-clinical; pharmacokinetic; pharmacodynamic; metabolomic and pharmacogenomic studies 3) to develop improved biomarkers of hypotension 4) to develop and adapt a formulation of Dobutamine suitable for newborns with the aim to apply for a Paediatric Use Marketing Authorisation. The NEO-CIRC consortium includes international experts in neonatal medicine, pharmacology, pharmacogenomics, drug formulation and pre-clinical neonatal models and an experienced group of experienced multicentre clinical trials NICU’s. Outcomes anticipated include improved biomarkers of organ perfusion; a new consensus definition of neonatal circulatory failure and answers to key clinical practice uncertainties, including variability of response to Dobutamine in common pathophysiologies seen in newborn infants impact on longer term developmental outcomes so important to the patients, families and wider society.

Keywords: dobutamine,clinical trial,randomised,puma,phamacogenomics,pharmacodynamics,neonates,paediatrics,superior vena cave flow,nirs,aaeg
Diagonal Interventions to Fast-Forward Enhanced Reproductive Health (DIFFER)

Framework: FP7 — Cooperation
Programme: Health
Destination: Optimising the delivery of healthcare to European citizens
Action type: Collaborative project
Countries involved: Belgium,South Africa,United Kingdom,India,Kenya,Mozambique
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2016-09-30
Duration (months): 60.0
Total project cost (EUR): 3732146.21
EU funding (EUR): 2940882.0
Participants: 6
Project status: CLOSED

Improving women’s sexual and reproductive health (SRH) requires innovative strategies to maximise potential synergies between components of care. Most adverse reproductive health outcomes stem from unintended pregnancy, and acquisition and transmission of reproductive tract infections. Although proven solutions exist, their implementation has been fragmented, with limited population impact, and little access for populations most at risk, such as sex workers. Integration of SRH services is key to achieving universal access to reproductive health. However, with weakened health systems and an HIV pandemic, the way forward is uncertain. The essential package of services and models for delivering them at high coverage in resource-limited settings are unclear. To address this, we propose a ‘diagonal’ strategy, incorporating both ‘horizontal’ health systems strengthening and more targeted ‘vertical’ approaches. Horizontal programmes can reach large numbers of women, while vertical programs target high-risk populations, difficult to reach through a horizontal approach. The aim is improved SRH services through identifying best practices in delivering a combined package of interventions for general population women and female sex workers. The research will occur in Kenya, Mozambique, South Africa, and Mysore, India by a consortium of 3 African, 1 Indian and 2 European partners. Detailed situation and policy analyses will be conducted in each country, with key stakeholder and community participation, and will inform the design of context-specific interventions to be implemented as feasible and acceptable packages of interventions. We will apply health systems research methodology to evaluate effectiveness and sustainability, and to identify the determinants of successful, sustainable and replicable interventions. This project will help to define packages of SRH services and models for delivery that meet the needs of all women and impact positively on their health.

Keywords: reproductive and sexual health targeted interventions integration novel
Gaining sage on the Epoetins' saga: assessing long term risks and advancing towards better Epoetin driven treatment modalities (EPOCAN)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Collaborative project
Countries involved: Israel,United Kingdom,Switzerland,Germany,Spain,Netherlands,Netherlands,Austria,Austria,Germany,Germany
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2014-09-30
Duration (months): 36.0
Total project cost (EUR): 3927556.8
EU funding (EUR): 2995103.6
Participants: 13
Project status: CLOSED

EpoCan aims to develop and implement a comprehensive interdisciplinary strategy to assess the long-term risks of erythropoietin (EPO) and its derivatives (epoetins) on tumour growth progression and thromboembolic events in cancer patients, cardiovascular events, and the development of cancer in chronic kidney disease. Approximately 400,000 patients across Europe receive epoetins treatment each year. Recent meta-analysis data have raised concerns over increased mortality in some patient groups. Hence the urgent need to evaluate the risk-benefit ratio of epoetin treatment and its potential long-term effects. EpoCan brings together a multidisciplinary consortium of 12 world leading academic, industrial and medical partners, with long-standing, complementary expertise in haemostasis, oncology and EPO biology. EpoCan aims to (1) Identify, detect and measure possible long-term hazards of epoetin treatment; (2) Develop novel prognostic tools and new complementary therapeutic reagents: (3) Evaluate the risk-benefit ratio to pave the way for new safety and efficacy criteria. EpoCan will: (a) Utilize a wide array of cellular models to thoroughly analyze EPO/EPO receptor(EPO-R)interaction and signalling, to define the relationship between EPO-R expression in tumour samples and the clinical outcome in cancer patients; (b) Establish and test new, personalized, predictive tools (EPO-R peptide antagonists, novel specific anti-EPO-R monoclonal antibodies, thromboembolic tests); (c) Create new murine models as hosts for tumour implantation subjected to EPO and derivatives established above; (d) Screen and analyze clinical databases; (e) Define models to predict hazardous versus safe/beneficial roles of epoetins in the treatment of cancer and kidney failure associated anaemia. Data obtained will be integrated into coherent models using novel computational algorithms developed for EpoCan. Results are expected to have broad ramifications, with special relevance for clinical oncology.

Keywords: cancer,tumor,thrombosis,cardiovascular events,epoetin treatment
Trusted Computing for European Embedded devices (TOISE)

Framework: FP7 — Cooperation
Programme: Joint Technology Initiatives (Annex IV-SP1)
Theme: Public-private partnerships
Destination: Electronic Numerical Integrator and Computer
Action type: Collaborative project
Partnership: ENIAC (Art-185)
Countries involved: Spain,France,France,Greece,Italy,Belgium,France,France,Spain
Call:  (ENIAC-2010-1, 2010)
Start date: 2011-01-01
End date: 2013-12-01
Duration (months): 35.0
Total project cost (EUR): 245845524.0
EU funding (EUR): 3617522.0
Participants: 20
Project status: CLOSED

For the future European applications such as Smart Grids for electricity network, smart low energy controlled home appliance, smart logistics and monitoring of goods, environmental or infrastructure sensor networks, and more generally more wireless communications and more networking functionalities, a number of technologies need to be developed and put in place to make the solutions smarter and more secure. TOISE proposes to address the secure tamper resistant solutions needed by the related embedded applications. Trusted Computing now in practise for the PC and workstation area provides a proven approach face to new attacks, by implementing a chain of authentication and integrity from the boot of the computing platform to the applications set up. The objective of TOISE is to define, develop and validate trust hardware and firmware mechanisms applicable both to lightweight embedded devices and as security anchors within related embedded platforms. The aim is to maintain Europe as a worldwide player in the field of efficient implementation of secure integrated devices to address the future European applications. A large initiative is proposed to align a common European position in the area. This will be actually a effort from major European semiconductor, fables and foundry players (Austriamicrosystems, Atmel, Infineon, Numonyx, NXP and STMicroelectronics), four IP providers (Intrinsic-ID, Magillem, Secure IC, Virage Logic) for PUF and secure IP infrastructure, two SME experts in Security solutions or evaluation labs (Brightsight, Fox-IT), five SME experts in Power line communications (AZCom), Metering (Elster), Energy management (MW Energie AG, Mixed Mode), Wireless network for Energy management and Public Health and Administration (TST), competent research groups in the participating countries to support related R&D (Cea Leti and Telecom ParisTech, CNM and UC, FHG SIT and RWTH, ICCS, PoliMi and UniMiB, TUE, BUT),and leaders in the market of secure and safety

Keywords: smart grids,secure communicationst,smart logistics,trusted computing,secure anchors,lightweight secure ic