Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
The Role of Beta-Adrenergic Signaling in Cardiac Progenitor Cell Activation after Myocardial Infarction (HEART BETAS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2013-IIF, 2013)
Start date: 2015-04-14
End date: 2017-04-13
Duration (months): 24.0
Total project cost (EUR): 202405.8
EU funding (EUR): 202405.8
Participants: 1
Project status: CLOSED

Cardiovascular diseases are a leading cause of mortality in the industrialized world with myocardial infarction (MI) being one of the common pathological events. Cardiac progenitor cells (CPC) are a progenitor cell population within the myocardium and are activated after MI to proliferate, migrate to the infarct site, and participate in cardiac regeneration. CPC are a current therapeutic target to diminish cardiac injury after a MI. After a MI, the beta-adrenergic system gets activated due to excessive concentrations of catecholamines accumulating in the myocardium. Interestingly, beta-2 adrenergic signaling has been suggested to promote CPC proliferation. It is currently unknown whether resident CPC could be affected by β-adrenergic signaling therapies. We therefore propose the general hypothesis that beta2-adrenergic receptor signaling after a MI favors the activation of endogenous CPC. We will use a mouse model of MI to evaluate the activation of CPC after treatment with beta-adrenergic agonists/antagonists. CPC will be analyzed by flow cytometry and immunohistochemistry. Cardiac outcomes (infarct size and arrhythmic events) will be correlated to the activation of the CPC. We will further investigate the hypothesis that beta2-adrenergic signaling mediates CPC activation through the regulation of intracellular calcium. We will treat murine and human CPC with beta-adrenergic agonists/antagonists and examine changes in intracellular calcium flux. We will correlate the effect of beta-adrenergic signaling on CPC proliferation and migration in vitro to calcium handling. Validation of our hypothesis would begin to dissect the natural molecular signals that are an integral part of myocardial healing.

Keywords: myocardial infarction,cardiac progenitor cells,beta-adrenergic signaling,calcium signaling
The Influence of parvalbumin neurons from the medial setum and diagonal band complex on medial entorhinal cortex activity (SEPTOENTOCIRCUITS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IIF, 2013)
Start date: 2014-04-01
End date: 2016-03-31
Duration (months): 24.0
Total project cost (EUR): 231283.2
EU funding (EUR): 231283.2
Participants: 1
Project status: CLOSED

Cognition and memory result from communication between specific populations of neurons in our brains. In the medial entorhinal cortex (MEC), representations of location that are crucial for spatial cognition and memory are generated by neurons called grid cells. The rate at which these neurons fire action potentials can be decoded into fields that for m a hexagonal grid spanning the environment. In addition to the action potential rate, the information about spatial location is also encoded by the timing of action potentials relative to the phase of local theta frequency oscillations in network activity. The action potential rate and timing codes require synaptic input from a subcortical structure called the medial septum and diagonal band complex (MS-DB). Yet, we know very little about how projections from the MS-DB influence neurons in the MEC. I propose to establish principles whereby a major subtype of MS-DB neurons, which express the inhibitory neurotransmitter GABA, influence activity of neurons in the MEC. I will combine optogenetic tools, to selectively activate GABAergic inputs from the MS-DB, with state of the art in vitro and in vivo electrophysiological recordings to identify and characterize their targets in the MEC. My approach will include the use of a new multi electrode array recording method that I will transfer to Europe, which will allow me to identify targets of MS-DB GABAergic neurons by simultaneously sampling large populations of neurons in the MEC. During my PhD I was the first to publish this method, which is currently not utilized in Europe. The proposal will advance the understanding of cellular and circuit mechanisms for spatial cognition and memory. It will also contribute to identification of design principles for biologically based computational devices for navigational control systems and new approaches to treating disorders such as Alzheimer’s, epilepsy and schizophrenia in which the MEC is implicated.

Keywords: medial septum,entorhial cortex,multi electrode array,in vivo virtual reality,electrophysiology,optognetics,aav.
Post-glacial recolonisation and Holocene anthropization impact on populations of shrews and hedgehogs from Western Europe inferred from zooarchaeology, historical biogeography and ecological modeling (SMALL_MAM_RECOL)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-05-05
End date: 2016-05-04
Duration (months): 24.0
Total project cost (EUR): 194046.6
EU funding (EUR): 194046.6
Participants: 1
Project status: CLOSED

At the end of last glaciation, ca. 15 000 cal. yrs ago, small mammals which had receded in the glacial refuges of southern Europe during the last pleniglacial started to spread again northward. This movement, which lasted several millenia -and which is still operating in a few cases- has been investigated through a number of phylogeographic works relying chiefly on molecular grounds so far. Comparatively few has been done on the basis of actual zooarchaeological data, especially for insectivores, often neglected in palaeoenvironmental and palaeoclimatic reconstructions. Moreover, phylogeographical hypotheses derived from molecular data are strongly limited by human perturbations (e.g. anthropisation of the landscape, introduction of alien species, isolation of ecosystems) which have remodelled the phylogenetic patterns of many European taxa since the appearance of agriculture ca 7500 yrs ago. What we intend to do here is to reconstruct the process of post-glacial recolonisation in several species of shrews and of the European hedgehog in Western Europe on the basis of geo-referenced and well dated occurences. For this we will rely on 1) the I2AF databases, hosted at the MNHN and which holds several thousands of bioarchaeological records, 2) data derived from the literature, 3) the production of new data by the identification of insectivores in key series in Spain, France, Belgium, Ireland and Britain. These data will be modelled using ecological niche modelling and integrating data on climate, vegetal environment and coastlines, which significantly evolved during this period. Thus, we hope to produce a dynamic model contributing 1) to understand how small mammal communites have formed at the beginning of the Holocene, and 2) to reconstruct how was the distribution of insectivore taxa prior to the anthropisation of natural environments which took place during the last 7500 years. This could have important outputs for the management and conservation of the studied species.

Keywords: zooarchaeology,small mammals,western europe,post-glacial recolonisation,databases,phylo-geography,ecological modeling
Synthesis of Two-Photon Optimized 'Caged' Compounds for Neuroscienes (LIGHTLAB-TOOLS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-11-01
End date: 2016-10-31
Duration (months): 24.0
Total project cost (EUR): 194046.6
EU funding (EUR): 194046.6
Participants: 1
Project status: CLOSED

Progress in science requires the development of new or better experimental tools. Photolysis has provided a way to study kinetics of ligand activated signaling in situ at inaccessible intracellular and extracellular receptors for three decades. It can now be combined with laser microscopy to provide high resolution spatio-temporal kinetics of receptors in situ, for photo-stimulation or photo-inhibition to study dendritic integration and networks, or for studying compartmentalization and distribution of receptors. The main obstacles to its improved application in neuroscience are the poor depth of penetration in neural tissue, a few tens of microns with one-photon excitation, and the requirement for better photolysis efficiency. Two-photon photolysis has inherently better resolution deep in tissues but needs much more efficient photolysis to permit brief exposures at low concentrations without phototoxicity. We plan to develop new caged neuroactive amino acids based on Laport symmetry-allowed aminoquinoline constructs with large two-photon cross-sections, high water solubility and minimal pharmacological interference. Preliminary results showed greater efficiencies than existing cages in photochemical studies and fast activation of synaptic glutamate receptors. The synthesis has been rationally simplified by applying novel methods, and the ligand addition forms a last step, allowing considerable flexibility in the range of neuroactive ligands that can be readily functionalized. The optimized molecular tools will be used to investigate glutamate receptor properties in situ in cerebellar Purkinje neurons and the interaction between fast and metabotropic glutamate receptors at the same synapses. Furthermore caged inhibitory amino acids GABA and glycine will be prepared and used to study the effects of photo-inhibition of individual cells, singly and with multi-spot illumination, on network activity.

Keywords: organic synthesis,photochemistry,photolysis,drug delivery,neurophysiology,synaptic transmission
Science for Society Solutions (S4S): Bringing Translational Science for Drylands Earth and Environmental Sciences into the Mainstream (S4S)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2013-IIF, 2013)
Start date: 2014-09-01
End date: 2016-08-31
Duration (months): 24.0
Total project cost (EUR): 223002.2
EU funding (EUR): 223002.2
Participants: 1
Project status: CLOSED

The larger goal of the S4S project is both ambitious and significant: make science more relevant and responsive to society. Despite significant advances in the drylands Earth and environmental sciences, successful application of research findings remains less than ideal. Whether it’s moving research to practice or educating the public on the environmental challenges of our time, our track record is poor. Successful adaptation to environmental change requires a theoretical and practical understanding of coupled natural-human systems as well as advances in bridging knowledge systems and the science-society gap. To be effective, this means a “translational science” approach that promotes the capture and integration of scientific and local knowledge, addresses the influences of scale (biophysically, socially, institutionally), encourages mutual learning among all parties, and builds capacity as part of the process. The facilitation and translation of information and meanings among stakeholders can lead to the co-production of knowledge, more informed decision making, and in a very pragmatic way, more effective use of assessments and other products of scientific discovery. This will be accomplished by reinforcing European research excellence through knowledge sharing with the view to developing mutually beneficial access to the state-of-the-art approaches for effective science translation, knowledge transfer, stakeholder engagement, decision aiding and the diffusion of innovation. How? mobilize both translational scientists and drylands scientists, identify and compile patterns of success in a wiki, create customizable training modules, demonstrate the added value, and facilitate the diffusion of innovation through multiple communication and knowledge management channels. The intended outcome: empower scientists and practitioners (public & private) to make science more relevant and responsive to society.

Keywords: science and society,translational science,knowledge transfer,stakeholder engagement,environmental education,public engagement,diffusion of innovation,decision support,adaptation
Developing smart Coordination Polymer Nanoparticles as Biomedicine for Metastatic Neuroblastoma (NANOCPPS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2015-02-16
End date: 2017-02-15
Duration (months): 24.0
Total project cost (EUR): 173370.6
EU funding (EUR): 173370.6
Participants: 1
Project status: CLOSED

Metastatic neuroblastoma is one of the most challenging malignancies of childhood, being associated with the highest death rate in pediatric oncology (20%). Moreover its prognosis is very poor, practically incurable, what shows the inability of nowadays chemotherapy to eradicate all the illness, underlining the need for novel therapeutic approaches. A current study of the European Group for study of the Neuroblastoma has shown profits in the survival of patients by means of the combination of several drugs (protocol COJEC: vincristine, carboplatin, etoposide and ciclofosfamide). However, such treatment shows a very important deep medullary aplasia as a secondary effect. Our hypothesis is that encapsulation of the NB drug cocktail can significantly improve nowadays disease treatment in such: I) will protect drugs from degradation before reaching cancer cells, II) will ensure their simultaneous actuation and III) last but not least, it will allow us to minimize undesirable medullary aplasia side effects upon specific vectorization of the drug cocktail to the target cells with targeting agents able to address GD2, a glycolipid highly expressed on the cell surface of neuroblastoma. Such exigent specifications require a unique multifunctional system that not all the reported drug carriers can achieve. Our choice is a new family of coordination polymer (CP) nanoparticles rrecently used with this aim by the host group due to their advantages: I) can encapsulate multiple active principles with high yield within the same particle, II) the presence of biocompatible metal ions can add additional fluorescence properties that allow us to follow the cell internalization and biodistribution, III) nanoparticles can be functionalized with specific targeting biomolecules and IV) preliminary in vitro cytotoxicity assays already showed that the encapsulated drugs could be effectively used to induce the cell death.

Keywords: coordination polymer particles,nanoscale materials,drug loaded nanocapsules,neuroblastoma,drug delivery,supramolecular chemistry,in vitro toxicity and biomedicine
A novel Androgen Synthesis Pathway in treatment-REsistant Prostate Cancer (ASPIRE-PC)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-03-01
End date: 2015-07-31
Duration (months): 12.0
Total project cost (EUR): 110803.2
EU funding (EUR): 110803.2
Participants: 1
Project status: CLOSED

Prostate cancer (PC) is the most prevalent non-cutaneous cancer in men and leads to high morbidity and mortality. Disseminated PC is treated by hormonal treatment in order to block intratumoral activation of the androgen receptor (AR) by 5α-dihydrotestosterone (DHT). Despite this treatment, eventually all patients develop castration-resistant disease (CRPC) which is accompanied by poor prognosis. Novel androgen synthesis and receptor inhibitors improve patient survival in CRPC, demonstrating the crucial role of residual androgen presence in PC despite castration. Besides the classic DHT synthesis pathway through testosterone, recent studies in humans have shown formation of DHT through an alternative pathway that does not require testosterone as an intermediate. Activity of this alternative androgen synthesis pathway is dependent on the presence of specific steroidogenic enzymes. Results of preliminary preclinical and clinical research show that levels of alternative pathway intermediates are increased in CRPC. Our goal is to investigate the activity and relevance of this novel pathway during progression of PC. The contribution of the alternative pathway to DHT-initiated AR activation will be explored using previously established in vitro models and sensitive steroid detection methods. This translational study will serve to discover novel targets for inhibition of intratumoral DHT synthesis and subsequent (CR)PC growth.

Keywords: prostate cancer,steroidogenesis,(dihydro)testosterone,alternative pathway,castration resistance
Astrocyte regulation of circadian behavior (ASTROCLOCK)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Italy
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-05-01
End date: 2016-04-30
Duration (months): 24.0
Total project cost (EUR): 241567.6
EU funding (EUR): 241567.6
Participants: 1
Project status: CLOSED

The human brain contains more than 100 billion cells, the majority being non-excitable glial cells, remarkably coordinated by an intrinsic clock that produce a circadian rhythm in their physiology and behavior. Circadian alterations affect human performances, productivity and are associated to increased risk of human-error related accidents and to a variety of brain disorders (e.g. sleep disorders). However, neuropharmacological R&D faces the lack of knowledge on how this clock signaling is hierarchically orchestrated within so many brain cells to lead to the cycle-to-cycle precision of circadian rhythmicity. Recent studies suggest that astrocytes (the most abundant cells of the brain) actively participate in the modulation of physiological and circadian behavioral processes in invertebrates. Although astrocytes are directly involved in the regulation of synaptic neuronal signaling (“tripartite synapse”), the role of astrocytes in controlling circadian behavior in mammals is largely unknown. This projects converges an original multidisciplinary research program, spanning the fields of molecular neurobiology, neuroelectronics and circadian biology, to unravel the molecular and functional mechanisms by which neurons and astrocytes cooperate to influence circadian rhythmicity in mammals. To do so, innovative genetics, molecular profiling (deep sequencing), behavioral, imaging and electrophysiological approaches will be used. The results of this proposal will lead to a deeper understanding on circadian rhythms in the brain and to the potential identification of new cellular and signaling targets for neuropharmacology.

Keywords: mouse,brain,circadian biology,astrocytes,astrocytes to neuron communication,in vivo neurophysiology,neurotechnology,neurobehaviour,molecular and cellular mechanisms,deep-sequencing mirna
Assessing suppression of methanogenesis in wetlands by electron accepting and polyphenolic moieties in natural organic matter (NOMSUPPRESSCH4)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Switzerland
Call:  (FP7-PEOPLE-2013-IIF, 2013)
Start date: 2014-04-01
End date: 2016-03-31
Duration (months): 24.0
Total project cost (EUR): 207928.8
EU funding (EUR): 207928.8
Participants: 1
Project status: CLOSED

Wetlands store between 15 and 30% of the global soil carbon pool as dissolved and particulate organic matter (DOM and POM). Wetlands are also the largest natural source of atmospheric methane (CH4) and given the high warming potential of CH4, formation and loss processes of CH4 in wetlands have received considerable research interest. Yet, our understanding of methanogenesis in wetlands is incomplete. Recent studies have implicated DOM and POM in two processes that suppress methanogenesis in wetlands. The first is utilization of DOM and POM as terminal electron acceptors (TEAs) in anaerobic microbial respiration. Electron transfer to OM is thought to competitively suppress methanogenesis. The second process is the direct inhibition of methanogens by polyphenolic DOM constituents. The goal of the proposed research is to quantify the importance of these two processes by incubating natural wetland samples in the laboratory and selectively perturbing them to study the two processes. The importance of DOM and POM as TEAs will be assessed by quantifying changes in their redox states during anoxic incubations using analytical electrochemistry combined with monitoring the formation of CH4 and carbon dioxide. Incubation experiments with alternating anoxic and oxic conditions will be carried out to determine whether electron transfer to OM samples is reversible and, thus, whether suppression of methanogenesis via this process is sustained over repeated redox cycles in periodically anoxic wetlands. The potential inhibitory effects of polyphenolic DOM on methanogens will be assessed by measuring changes in methanogenesis in anoxic samples after addition of both natural and model polyphenols. The proposed research will derive a mechanistic understanding of the two studied processes. This understanding will allow transfer of the results from the lab-scale investigations to processes at the field scale and will help to improve wetland management policies.

Keywords: dissolved organic matter,particulate organic matter,wetlands,anaerobic respiration,methanogenesis,redox,analytical electrochemistry,polyphenolic substances,ombrotrophic bogs