Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Molecular Studies of Astrocyte Function in Health and Disease (ASTROFUNC)

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: Belgium
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1490168.4
EU funding (EUR): 1490168.4
Participants: 1
Project status: CLOSED

Brain consists of two basic cell types – neurons and glia. However, the study of glia in brain function has traditionally been neglected in favor of their more “illustrious” counter-parts – neurons that are classed as the computational units of the brain. Glia have usually been classed as “brain glue” - a supportive matrix on which neurons grow and function. However, recent evidence suggests that glia are more than passive “glue” and actually modulate neuronal function. This has lead to the proposal of a “tripartite synapse”, which recognizes pre- and postsynaptic neuronal elements and glia as a unit. However, what is still lacking is rudimentary information on how these cells actually function in situ. Here we propose taking a “bottom-up” approach, by identifying the molecules (and interactions) that control glial function in situ. This is complicated by the fact that glia show profound changes when placed into culture. To circumvent this, we will use recently developed cell sorting techniques, to rapidly isolate genetically marked glial cells from brain – which can then be analyzed using advanced biochemical and physiological techniques. The long-term aim is to identify proteins that can be “tagged” using transgenic technologies to allow protein function to be studied in real-time in vivo, using sophisticated imaging techniques. Given the number of proteins that may be identified we envisage developing new methods of generating transgenic animals that provide an attractive alternative to current “state-of-the art” technology. The importance of studying glial function is given by the fact that every major brain pathology shows reactive gliosis. In the time it takes to read this abstract, 5 people in the EU will have suffered a stroke – not to mention those who suffer other forms of neurotrauma. Thus, understanding glial function is not only critical to understanding normal brain function, but also for relieving the burden of severe neurological injury and disease

Keywords: glia,astrocyte,gliotransmitter release
Resolving the Neuropharmacology and Genetics of Zebrafish Sleep (ZFISHSLEEP)

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: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1902750.0
EU funding (EUR): 1902750.0
Participants: 1
Project status: CLOSED

Sleep is a fundamental process, yet the genetic and neural mechanisms that regulate sleep are largely unknown. We have developed the zebrafish as a model system to study the regulation of sleep because it combines the genetics of invertebrates with the basic brain structures that regulate sleep in humans. We previously designed high throughput behavioural assays to measure sleep behaviours in the fish and used genetic tools to demonstrate that the wake-regulating hypocretin/orexin (Hcrt) system is functionally conserved in the zebrafish. We have also used our assays to perform a small molecule screen and identified both conserved and novel candidate regulators of sleep in zebrafish. In Aim 1, we will observe the behaviour of wild type and Hcrt receptor mutants to a panel of small molecules known to alter zebrafish sleep. This aim tests the hypothesis that these compounds exert their effects on sleep and wake through the Hcrt system. In Aim 2, we will follow-up on the compounds that had differential effects in the mutants. We will monitor the activity of Hcrt neurons in response to drugs using a new neuroluminescent technique to observe the activity of neurons in freely behaving zebrafish larvae. This Aim will extend the behavioural data to the level of neural circuits. In Aim 3, we will use new methods to globally observe neuronal activity in the zebrafish brain to extend our analysis to neurons thought to interact with the Hcrt system. By observing activity across the sleep/wake cycle, we may also uncover novel sleep regulating neurons. Overall, this project takes a multidisciplinary approach to the study of sleep and the Hcrt system, leveraging new methods from chemical biology, molecular genetics, and behavioural neuroscience in the zebrafish. As little is known about the mechanisms and sites of action for most sleep-altering compounds, any progress would advance the sleep field and could have clinical relevance to the treatment of sleep disorders.

Keywords: sleep,chemical biology,drug screening,zebrafish,neuropeptides,neuropharmacology,behavioral genetics
A systems and targeted approach to alternative splicing in the developing and diseased heart: Translating basic cell biology to improved cardiac function (CARDIOSPLICE)

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: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2017-06-30
Duration (months): 66.0
Total project cost (EUR): 1499191.0
EU funding (EUR): 1499191.0
Participants: 1
Project status: CLOSED

Cardiovascular disease keeps the top spot in mortality statistics in Europe with 2 million deaths annually and although prevention and therapy have continuously been improved, the prevalence of heart failure continues to rise. While contractile (systolic) dysfunction is readily accessible to pharmacological treatment, there is a lack of therapeutic options for reduced ventricular filling (diastolic dysfunction). The diastolic properties of the heart are largely determined by the giant sarcomeric protein titin, which is alternatively spliced to adjust the elastic properties of the cardiomyocyte. We have recently identified a titin splice factor that plays a parallel role in cardiac disease and postnatal development. It targets a subset of genes that concertedly affect biomechanics, electrical activity, and signal transduction and suggests alternative splicing as a novel therapeutic target in heart disease. Here we will build on the titin splice factor to identify regulatory principles and cofactors that adjust cardiac isoform expression. In a complementary approach we will investigate titin mRNA binding proteins to provide a comprehensive analysis of factors governing titin’s differential splicing in cardiac development, health, and disease. Based on its distinctive role in ventricular filling we will evaluate titin splicing as a therapeutic target in diastolic heart failure and use a titin based reporter assay to identify small molecules to interfere with titin isoform expression. Finally, we will evaluate the effects of altered alternative splicing on diastolic dysfunction in vivo utilizing the splice deficient mutant and our available animal models for diastolic dysfunction. The overall scientific goal of the proposed work is to investigate the regulation of cardiac alternative splicing in development and disease and to evaluate if splice directed therapy can be used to improve diastolic function and specifically the elastic properties of the heart.

Keywords: alternative splicing,pharmacology,cardiac development
Silicon transport proteins in biological nanoscience and synthetic biology (IMPLANT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: United Kingdom
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-10-01
End date: 2016-09-30
Duration (months): 60.0
Total project cost (EUR): 1487476.0
EU funding (EUR): 1487476.0
Participants: 1
Project status: CLOSED

This interdisciplinary proposal will investigate whether the activity of a unique family of membrane transport proteins can be harnessed to develop novel strategies for the bioinspired fabrication of nanoscale materials and provide new directions in synthetic biology. Silicon transporters (SITs) are integral membrane proteins that were first identified in the diatoms, single–celled eukaryotic algae that surround themselves with a cell wall of hydrated silica. The biosynthesis of this ‘glass house’ depends upon the uptake of silicic acid, the soluble form of silica, from the environment. The SITs bind silicic acid with high affinity and transport it across the cytoplasmic membrane into the cell. Under this proposal the SITs will be recombinantly expressed and purified before being reconstituted into synthetic liposomes. The resulting proteoliposomes will be energized to drive SIT-dependent transport of silicic acid into the interior lumen. Since the lumen has dimensions on the nanometer length scale and attolitre volume, the proteoliposomes will act as discrete nanoreactors for the synthesis of silica nanoparticles. Using SIT proteins to deliver silicic acid to the growing nanoparticle offers an unprecedented degree of tunable kinetic control over the synthetic conditions that, together with the lumen microenvironment, may induce novel particle morphologies or properties. This principle will be extended in two further directions. First, encapsulating preformed inorganic nanoparticles in the liposome lumen will lead to the formation of core-shell nanoparticles with a functional core and passive silica shell. Using SITs to control the supply of the synthetic precursor will provide unparalleled tight control over the thickness of the silica shell. A second element will create a diatom protocell by incorporating silica-condensing peptides into the lumen in order to generate silica nanostructures. This will establish a unique new methodology for nanoscale synthesis.

Keywords: nanotechnology,membrane protein,membrane transport
Optogenetic examination of the role of feedback on visual processing and perception (NEUROOPTOGEN)

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: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-07-01
End date: 2017-06-30
Duration (months): 60.0
Total project cost (EUR): 1903114.0
EU funding (EUR): 1903114.0
Participants: 1
Project status: CLOSED

We need to understand the brain mechanisms of perception and cognition in order to develop treatments for disorders in which these abilities fail, such as schizophrenia, attention-deficit-hyperactivity disorder or autism. Over the past half-century neurophysiologists have enormously advanced our knowledge of how the feed-forward connections give rise to the response properties in the visual cortex. However, although we know from anatomy that most afferents in cortex constitute feedback projections, their function is still largely unknown. Visual perception in humans and monkeys depends on context. These perceptual phenomena are thought to be mediated by feedback, and many are altered in schizophrenic patients. Understanding the role of feedback is therefore important not only for unraveling fundamental mechanisms of cognition, but also for addressing their dysfunction in cognitive disorders. Until now technical limitations have made it nearly impossible to test the role of feedback. Novel approaches allow us to examine the role of cortico-cortical feedback in visual perception in the behaving monkey. We will use optogenetic techniques and retrograde viral vectors (lentivirus pseudotyped with rabies glycoprotein) to target specific monosynaptic cortico-cortical projections in vivo. By expressing the light-sensitive proteins channelrhodopsin2 (ChrR2) or archaerhodopsin (Arch) in these projection neurons, we can activate (ChR2) or inactivate (Arch) them with light. We will combine this approach with multi-channel electrophysiology, behavior and computational analyses. We will first quantify the effect of (in)activating cortico-cortical feedback from visual cortex V2 on the neuronal responses in the primary visual, and then on the monkey’s visual perception during tasks manipulating attention. If successful, this work will help advance our functional understanding of feedback, and may open the possibility to examine the function of any connection in the primate brain.

Keywords: awake behaving primate,optogenetics,viral vectors
DEFINING THE MECHANISMS OF AGE-RELATED MUSCLE LOSS: FOCUS ON AUTOPHAGY (MYOPHAGY)

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-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1250000.0
EU funding (EUR): 1250000.0
Participants: 1
Project status: CLOSED

Muscle loss occurs in many diseases including cancer, AIDS, diabetes, renal or cardiac failure and sepsis. The wasting of muscle mass is characterized by the activation of an atrophy program that coordinates the ubiquitin-proteasome and autophagy-lysosome systems. The simultaneous activation of these systems allows the breakdown of contractile proteins and the removal of organelles. Ageing sarcopenia and frailty are also characterised by progressive muscle loss. However, the mechanisms that are at the base of this weakness are obscure. Sarcopenia results in a progressive loss of mobility that decreases the quality of life and has major economic and social consequences. In fact the age-dependent muscle atrophy favour traumatic events, accident, fracture or illness which lead to aged person to become hospitalised and bed-ridden or housebound, thus -having a high mortality in the year following their accident. The signalling pathways, which regulate loss of proteins and organelles in muscle fibers, are just at the beginning to be understood. We have recently found that autophagy-lysosome system is critical to maintain muscle mass and that its alteration leads to muscle atrophy, weakness and to several features that are present in ageing sarcopenia. Thus, dissecting the regulation of autophagy system in skeletal muscle and its role in muscle homeostasis is crucial for developing new therapeutic tools to counteract sarcopenia. This project is an effort in this direction. We aim: i) to identify molecular mechanisms and pathways which are responsible for autophagy regulation in skeletal muscle and which may be targeted to combat age related muscle weakness, (ii) to dissect the cross-talk between muscle and nerve, (iii) to determine the cross-talk between autophagy-lysosome and ubiquitin-proteasome, iv) to translate the findings obtained in animal models to human skeletal muscles.

Keywords: skeletal muscle,autophagy,atrophy,ageing
Rapid Adaptive Nonlinear Gradient Encoding for Magnetic Resonance Imaging (RANGEMRI)

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-2011-StG_20101109, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 1497672.0
EU funding (EUR): 1497672.0
Participants: 1
Project status: CLOSED

The project is aimed at the development of novel approaches for flexible signal localisation and encoding in Magnetic Resonance Imaging (MRI) for applications in neuroscience, neurology, oncology and further areas. The Rapid Adaptive Nonlinear Gradient Encoding for Magnetic Resonance Imaging (RANGE) methodology is based on the concept of applying localised, generally nonlinear encoding fields to faster, customised and anatomically-aligned imaging. The increase in encoding efficiency originates from several key factors: (i) local fields can be tailored to reduce peripheral nerve stimulation and power requirements to allow for faster switching; (ii) localised character of the fields requires less encoding steps and (iii) ability to select curved anatomy-adapted regions allows to cover target volumes with less slices; (iv) local encoding along curved surfaces reduces partial volume effects, delivering data of identical quality with lower nominal resolution compared to a standard approach. Each of these aspects is expected to contribute a factor of at least 2 to 3, resulting in a total encoding efficiency boost of an order of magnitude. Flexible fields will also be used for very high order localised dynamic shimming, allowing to further increase acquired data quality. The technological backbone for the RANGE principle will be provided by a novel highly-integrated switchable matrix gradient coil. The new coil type will be able to generate both local nonlinear and global linear fields. Upon proper industrial realisation it is expected to match or even outperform traditional linear gradient coils, while providing an ultimate flexibility in generating rapidly switched localised fields. Hardware, methodology and operator interface to the scanning process will be developed to handle signal selection, localisation and encoding in curved nonlinear coordinates to streamline the application development and facilitate the transfer to clinical practice and neuroscientific research.

Keywords: magnetic resonance imaging,mri,functional mri,fast imaging,spatial encoding,cardiac imaging,abdominal imaging
Dengue research Framework for Resisting Epidemics in Europe (DENFREE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: France,United Kingdom,Germany,Thailand,Cambodia,Spain,France,Portugal,Finland,Cuba,French Polynesia,United Kingdom
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 8373688.07
EU funding (EUR): 5999062.0
Participants: 15
Project status: CLOSED

WHO estimates that one of the main consequences of global warming will be an increased burden of vector-borne diseases. Among these, dengue appears to be particularly problematic, with tens of millions of cases of dengue fever estimated to occur annually, including up to 500,000 cases of the life-threatening dengue hemorrhagic fever/dengue shock syndrome. In recent years, the global burden of dengue disease has been rising dramatically and this prolific increase has been connected to societal changes such as population growth, urbanization and the transport of infected hosts and vectors. In addition, rising temperatures and global climate change may lead to the expansion of the range of major mosquito vectors, extension of the transmission season in areas with currently circulating dengue virus and increase in the mosquito spp. vectorial capacity. Active surveillance to detect in-coming dengue virus (DENV) in regions at the limits of DENV circulation are an important initial step in the prevention of dengue epidemics in Europe. Asymptomatic infections likely play a crucial role in the initial invasion process and DENV transmission and, although hitherto ignored, must be addressed. Using retrospective and prospective data from Asia, the main objectives of the program are (1) to identify key factors determining dengue transmission, outcome of infection and epidemics; (2) the development of novel diagnostic tools to detect asymptomatic infections. We will estimate the risk of DENV spreading to uninfected areas, especially in Southern Europe where susceptible vector exists. The major tools generated will be predictive models that enable specific interventions to reduce epidemic probability and diagnostic methods for surveillance. Inherent in this approach is the belief that improved surveillance and diagnosis of the asymptomatic dengue carriers will contribute to effective intervention, especially during early stages of pathogen invasion into a naïve region.

Keywords: diagnostics,surveillance,dengue transmission,epidemiological models,asymptomatic infection
Resistance in Gram-Negative Organisms: Studying Intervention Strategies (R-GNOSIS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Netherlands,Switzerland,Belgium,Israel,France,France,United Kingdom,United Kingdom,Spain,Germany,France,Spain,Denmark,United Kingdom,United Kingdom,United Kingdom,Netherlands
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2017-03-31
Duration (months): 66.0
Total project cost (EUR): 15654161.2
EU funding (EUR): 11999999.0
Participants: 24
Project status: CLOSED

Antibiotics are a mainstay of public health, but their use has increased exponentially leading to the emergence of antibiotic resistance. The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) project combines 5 international clinical studies, all supported by highly innovative microbiology, mathematical modelling and data-management, to determine - in the most relevant patient populations - the efficacy and effectiveness of cutting-edge interventions to reduce carriage, infection and spread of Multi-Drug Resistant Gram-negative Bacteria (MDR-GNB). All work-packages will progress science beyond the state-of-the-art in generating new and translational clinically relevant knowledge, through hypothesis-driven studies focussed on patient-centred outcomes. The 5 clinical studies will investigate the following interventions: •A Point-Of-Care-Testing guided management strategy to improve appropriate antibiotic prescription for uncomplicated UTI in primary care. •Gut decolonization in outpatients with intestinal carriage of MDR-GNB. •A “test and prescribe” strategy, based on rapid diagnostic testing of faeces for MDR-GNB to optimize antibiotic prophylaxis in colo-rectal surgery. •Contact Isolation of patients with ESBL-producing Enterobacteriaceae in general hospital wards. •Three Decolonization strategies in ICUs. Seven laboratories across Europe will perform microbiological analyses, as well as unique quantitative experiments. All information will be integrated by 3 groups of mathematical modellers into highly innovative models to better understand and predict future trends and effects of interventions. The studies and analyses proposed in R-GNOSIS will generate a step-change in identifying evidence-based preventive measures and clinical guidance for primary care and hospital-based physicians and health-care authorities, to combat the spread and impact of infections caused by MDR-GNB in Europe.

Keywords: carriage,infection,spread multi-drug resistant gram-negative bacteria,decolonization,icu,antibiotic prophylaxis,contact isolation