Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Targeting the reproductive biology of the malaria mosquito Anopheles gambiae: from laboratory studies to field applications (ANOREP)

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: Italy
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-01-01
End date: 2015-12-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Anopheles gambiae mosquitoes are the major vectors of malaria, a disease with devastating consequences for human health. Novel methods for controlling the natural vector populations are urgently needed, given the evolution of insecticide resistance in mosquitoes and the lack of novel insecticidals. Understanding the processes at the bases of mosquito biology may help to roll back malaria. In this proposal, we will target mosquito reproduction, a major determinant of the An. gambiae vectorial capacity. This will be achieved at two levels: (i) fundamental research, to provide a deeper knowledge of the processes regulating reproduction in this species, and (ii) applied research, to identify novel targets and to develop innovative approaches for the control of natural populations. We will focus our analysis on three major players of mosquito reproduction: male accessory glands (MAGs), sperm, and spermatheca, in both laboratory and field settings. We will then translate this information into the identification of inhibitors of mosquito fertility. The experimental activities will be divided across three objectives. In Objective 1, we will unravel the role of the MAGs in shaping mosquito fertility and behaviour, by performing a combination of transcriptional and functional studies that will reveal the multifaceted activities of these tissues. In Objective 2 we will instead focus on the identification of the male and female factors responsible for sperm viability and function. Results obtained in both objectives will be validated in field mosquitoes. In Objective 3, we will perform screens aimed at the identification of inhibitors of mosquito reproductive success. This study will reveal as yet unknown molecular mechanisms underlying reproductive success in mosquitoes, considerably increasing our knowledge beyond the state-of-the-art and critically contributing with innovative tools and ideas to the fight against malaria.

Keywords: mosquito,reproduction,malaria,vector control,male accessory glands,seminal secretions,sperm,inhibitors of fertility
A Chemical Genomics Approach of Intracellular Mycobacterium tuberculosis Towards Defining Specific Host Pathogen Interactions (INTRACELLTB)

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: France
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2015-11-30
Duration (months): 60.0
Total project cost (EUR): 1982371.0
EU funding (EUR): 1982371.0
Participants: 1
Project status: CLOSED

Tuberculosis, caused by Mycobacterium tuberculosis is still a major threat to global health. Because the treatment of an infected individual requires more than six months of chemotherapy, compliance is low, which can result in the development of multidrug resistant (MDR-TB) strains. New drugs and new targets are needed to combat MDR-TB. A critical feature of the Mycobacterium tuberculosis bacillus is its ability to survive and even replicate within macrophages, making these host cells an ideal niche for persisting microbes. The goal of our project is to understand the biological mechanisms underlying the persistence of intracellular mycobacteria and to develop novel approaches to eradicate the bacillus from its hiding spot. To this end, we have been undertaking global approaches using visual phenotypic assays (relying on monitoring by automated confocal fluorescence microscopy) of the trafficking and replication of M. tuberculosis inside macrophages. Screening of a small interfering RNA library, a M. tuberculosis transposon mutant library and hundreds of thousands of small chemical molecules has led to the identification of key host and mycobacterial genes involved in the intracellular fate of M. tuberculosis, as well as chemicals able to prevent intracellular bacterial growth. Building on the considerable data generated and on the powerful high throughput / high content (HT/HC) confocal microscopy, our project is to further explore the signalling pathways used specifically by M. tuberculosis. We will focus on the in depth study of bacterial protein effectors belonging to the ESX and PPE families and of the SOCS family member CISH, which promotes intracellular mycobacterial survival. Finally, chemicals that target cellular partners of M. tuberculosis will constitute a new starting point for the development of drugs able to counteract this host response manipulation without directly targeting the pathogen, thereby overcoming the issue of the emergence of MDR-TB.

Keywords: chemical genomics high content imaging high throughput technologies
Follow the PAIN: Novel Somatotopically-Based Integrative Approach to Study Mechanisms of Detection, Transmission and Perpetuation of Nociceptive, Inflammatory and Neuropathic Pain (SIAMCP)

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: Israel
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-03-01
End date: 2016-02-29
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

The worst of evils - pain is one of the main reasons for seeking medical help. Chronic pain affects almost one fifth of the population of Europe and leads to exorbitant medical expenses as well as extreme suffering. Despite extensive efforts, effective pain treatment has remained elusive. Inadequate understanding of the mechanisms of pain prevents the development of effective therapies. In order to better understand pain mechanisms, a novel integrative approach is needed. This approach should: to investigate the fundamental site of signal detection; the nociceptive terminals and to establish an understanding of the progression from peripheral nociception to central pain perception. Our project aims to integrate analysis at different levels of pain perception in normal and pathological conditions in order to elucidate mechanisms underlying chronic pain. Our approach propose to study pain related mechanisms along somatotopically define neuroaxis of vibrissae-barrel system. Using this unique system where peripheral receptor directly corresponds to its central analyzer, we will first characterize noxious signal detection by single channels in individual nociceptive terminal. We will follow propagation of nociceptive signal and monitor activity-dependent changes in corresponding circuits at trigeminal nuclei, thalamus and cortex. We will study modulation in of synaptic connectivity in the spino-thalamo-cortical pathway in models of chronic pain. This multi-disciplinary project will incorporate ground-breaking imaging techniques and state-of-the-art electrophysiological, histological and behavioural experiments to study pain-related mechanisms at the molecular and cellular levels as well as at the level of neuronal networks and behaviour.

Keywords: nociception,nociceptor terminals,inflammatory pain,neuropathic pain,whisker,somatosensory
Population transcriptional genomics in humans using high throughput sequencing (POPRNASEQ)

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: Switzerland
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Gene expression is one of the marks of cellular state and function. The relative abundance of transcripts defines and is a result of the differentiation status of a cell. Interrogation of gene expression levels and patterns in the human and other genomes can be informative about perturbations from the average pattern due to external stimuli or internal factors such as genetic variants. Gene expression profiles have been extensively used to assess developmental processes, pathways contributing to cell differentiation, and predicting the outcome of disease status. Understanding the effects of genetic variation in basic cellular processes such as gene expression is key to the dissection of the genetic contributions to whole organism phenotypes. We propose to interrogate the transcriptome of primary fibroblasts, primary T-cells and EBV-transformed B-cell (lymphoblastoid cell lines or LCLs) from umbilical cords of 200 individuals of European descent using next generation sequencing (mRNAseq). A subset will also be interrogated for transcriptionally engaged RNA polymerases (GROseq) and protein abundance. These data will be analyzed for the detection of eQTLs and other genetic effects associated with variation in alternative splicing and other properties of the transcripts and dissection of the genetic effects from primary transcription to protein and their tissue specific effects. These data will be integrated with genome-wide association studies and other efforts to dissect the genetic basis of complex traits and diseases in humans. In addition, we will develop bioinformatic models to understand the fine scale regulatory signals that are responsible for the regulatory patterns observed and how sequence variants have an effect on them.

Keywords: population genomics,functional variation,expression qtls
Control of mouse metabolism by circadian clock-coordinated mRNA translation (CIRCATRANS)

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: 2011-03-01
End date: 2016-02-29
Duration (months): 60.0
Total project cost (EUR): 1475830.8
EU funding (EUR): 1475830.8
Participants: 2
Project status: CLOSED

The mammalian circadian clock plays a fundamental role in the liver by regulating fatty acid, glucose and xenobiotic metabolism. Impairment of this rhythm has been show to lead to diverse pathologies including metabolic syndrome. At present, it is supposed that the circadian clock regulates metabolism mostly by regulating the expression of liver enzymes at the transcriptional level. We have now collected evidence that post-transcriptional regulations play also an important role in this regulation. Particularly, recent results from our laboratory show that the circadian clock can synchronize mRNA translation in mouse liver through rhythmic activation of the Target Of Rapamycin Complex 1 (TORC1) with a 12-hours period. Based on this unexpected observation, we plan to identify the genes rhythmically translated in the mouse liver as well as the mechanisms involved in this translation. Indeed, our initial observations suggest a cap-independent translation during the day and a cap-dependent translation during the night. Identification of the different complexes involved in translation at this two different times and their correlation with the sequence, structure, and/or function of the translated genes will provide new insight into the action of the circadian clock on animal metabolism. In parallel, we will identify the signalling pathways involved in the rhythmic activation of TORC1 in mouse liver. Finally, we will study the consequences of a deregulated rhythmic translation in circadian clock-deficient mice on the metabolism and the longevity of these animals. Perturbations of the circadian clock have been linked to numerous pathologies, including obesity, type 2 diabetes and cancer. Our project on the importance of circadian clock-coordinated translation will likely reveal new findings in the field of regulation of animal metabolism by the circadian clock.

Keywords: circadian clock,translation,cell signaling,metabolism
Treatment of reperfusion injury using a mitochondrial targeted approach: towards a better understanding of the disease. (MITOCARE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: France,France,Norway,Denmark,Sweden,Denmark,Sweden,United Kingdom,France,Sweden,Denmark,Sweden
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2011-01-01
End date: 2013-12-31
Duration (months): 36.0
Total project cost (EUR): 8192211.15
EU funding (EUR): 5990959.0
Participants: 17
Project status: CLOSED

Current interventional treatment of acute myocardial infarction (AMI) focused on re-establishing cardiac reperfusion has significantly improved clinical outcome by reducing infarct size and mortality due to cardiac ischemia.It is now recognized that events triggered at reperfusion also result in cell death and may account for as much as 50% of the infarct volume, this being termed ischemia-reperfusion injury (IRI). Mitochondrial permeability transition pore (mPTP) opening appears to be a responsible for IRI and a recent small clinical trial with cyclosporine A shows that it is a feasible target for the development of new therapies to treat it. Since total infarct size is a major determinant of a patients risk to develop heart failure, treating IRI is expected to further reduce morbidity, mortality and the need for regenerative medicine following cardiac ischemia. By harnessing a multi-disciplinary consortium of clinical and basic scientists along with four SMEs, MitoCare brings state-of-the art expertise together to 1) better understand IRI pathophysiology and factors directly or indirectly influencing patient’s recovery or response to treatment; 2) investigate the translational usefulness of preclinical models; and 3) compare selected treatments. These objectives will be reached through the following work plan: A) a medium-scale phase II clinical study will evaluate the efficacy of a novel complementary therapy to PCI, the new mPTP modulator TRO40303, while at the same time 1) perform extensive sampling from subjects in the study for analysis of standard and emerging biomarkers; 2) identify confounding factors influencing patients’ outcomes. B) Parallel investigations in preclinical in vitro and in vivo AMI models. C) Statistical analysis of data from clinical and preclinical studies, to identify better diagnostic and prognostic endpoints in man and assess predictive utility of preclinical models.

Keywords: myocardium ischemia reperfusion injury biomarkers mitochondrial transition pore sme clinical trial translational research percutaneous coronary intervention confounders patients heart failure
Molecular mechanisms controlling leukocyte trafficking in the central nervous system (NEUROTRAFFICKING)

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: Italy
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-10-01
End date: 2014-09-30
Duration (months): 48.0
Total project cost (EUR): 1199880.0
EU funding (EUR): 1199880.0
Participants: 1
Project status: CLOSED

Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) represent the prototype of autoimmune chronic inflammatory diseases of the central nervous system (CNS). Migration of activated T cells across the blood-brain barrier represents a critical step in the pathogenesis of MS and EAE, and inhibition of lymphocyte trafficking in the CNS represents a powerful therapeutic approach in MS patients as well as in animal models of this disease. In recent years growing evidence show that immune cells and inflammation mechanisms play an unexpected role in other neurological diseases such as epilepsy. Our team has recently shown that seizures induce vascular inflammation and enhanced neutrophil and T cell adhesion in brain vessels. Inhibition of leukocyte-vascular interactions dramatically reduced seizures in an experimental model of epilepsy, suggesting leukocyte-endothelial interaction as a potential target for the prevention and treatment of epilepsy. The main goal of this project is to study the mechanisms controlling immune cell trafficking in neurological diseases such as MS and epilepsy in which inflammation has a detrimental role. We will first study novel molecular mechanisms controlling leukocyte-endothelial interactions in CNS microcirculation taking advantage of our established expertise in intravital microscopy studies. Leukocyte trafficking will be further followed inside CNS parenchyma by using two-photon microscopy, which will allow us to characterize leukocyte migration Overall, NEUROTRAFFICKING will generate fundamental knowledge to the understanding of the role of immune system in neurological disease and will unveil novel potential therapeutic targets for CNS inflammatory pathologies.

Keywords: leukocyte trafficking,experimental autoimmune encephalomyelitis,epilepsy,two-photon microscopy,intravital microscopy
Identifying mechanisms of information encoding in myelinated single axons (ENCODING IN AXONS)

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: Netherlands
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-04-01
End date: 2016-03-31
Duration (months): 60.0
Total project cost (EUR): 1994640.0
EU funding (EUR): 1994640.0
Participants: 1
Project status: CLOSED

A major challenge in neuroscience is to understand how information is stored and coded within single nerve cells (neurons) and across neuron populations in the brain. Nerve cell fibres (axons) are thought to provide the wiring to connect neurons and conduct the electrical nerve impulse (action potential; AP). Recent discoveries, however, show that the initial part of axons actively participates in modulating APs and providing a means to enhance the computational repertoire of neurons in the central nervous system. To decrease the temporal delay in information transmission over long distances most axons are myelinated. Here, we will test the hypothesis that the degree of myelination of single axons directly and indirectly influences the mechanisms of AP generation and neural coding. We will use a novel approach of patch-clamp recording combined with immunohistochemical and ultrastructural identification to develop a detailed model of single myelinated neocortical axons. We also will investigate the neuron-glia interactions responsible for the myelination process and measure whether their development follows an activity-dependent process. Finally, we will elucidate the physiological and molecular similarities and discrepancies between myelinated and experimentally demyelinated single neocortical axons. These studies will provide a novel methodological framework to study central nervous system axons and yield basic insights into myelin physiology and pathophysiology.

Keywords: myelin,cortex
Integration of Chikungunya research (ICRES)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: United Kingdom,Sweden,Estonia,Finland,France,France,Germany,Germany,Malaysia,United Kingdom,Spain,United Kingdom,Australia,Singapore
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2010-12-01
End date: 2014-11-30
Duration (months): 48.0
Total project cost (EUR): 5055096.51
EU funding (EUR): 2999938.6
Participants: 15
Project status: CLOSED

Since 2005 Chikungunya fever has affected millions of people producing a high fever and a debilitating arthralgia which can persist for months and progress to chronic arthritis. Chikungunya virus has been associated with periodic outbreaks of human disease and is spread by mosquitoes. The current epidemic rose to prominence in 2005/6 following infection of >250,000 people on La Réunion. The virus rapidly spread to other islands in the Indian Ocean, India and SE Asia. Chikungunya cases in returning travellers have been reported. In summer 2007 a traveller from India to Italy initiated a locally transmitted outbreak which included one death from encephalitis. The mosquitoes transmitting this infection are spreading and increasing in Europe and could spread as far north as the British Isles. There are diagnostics tests, these require standardisation. The pathogenic mechanisms leading to myalgia, arthralgia, rare encephalitis and chronic arthritis are unknown precluding rational therapeutic intervention. There are no antivirals. There is no licensed vaccine. This project will integrate the expertise of EU laboratories with a long and strong track record of research on alphaviruses with EU laboratories that started work on CHIKV following the outbreak in La Réunion and laboratories from SE Asia working on this virus. The project will generate new molecular and cellular tools for research and applied studies, including high-throughput screening and vaccines; standardise, quality assure and distribute key diagnostic tests and develop new ones; determine virus genetic changes across time, geographical regions and species; discover interactions between virus and human cells to inform rational design of therapeutics; study immune responses in the chronic disease in humans, including whether virus persists in joints, the cell types involved and the relationship to immune responses; characterise rodent and non-human primate models of acute and chronic infection to further study the pathogenesis and provide models for antiviral and vaccine screens; screen libraries of characterized pharmaceutical and bioactive compounds for antiviral activity and develop a vaccine which at the end of this project is ready to enter clinical trials.

Keywords: chikungunya,arbovirus,vaccine,antiviral,diagnostics,arthralgia,pathogenesis