Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Dynamics of second messengers in axon guidance: decrypting the codes (MESSENGER CODES)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Outgoing Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2007-4-1-IOF, 2007)
Start date: 2008-10-01
End date: 2011-09-30
Duration (months): 36.0
Total project cost (EUR): 239169.49
EU funding (EUR): 239169.49
Participants: 1
Project status: CLOSED

The mature nervous system is an intricate network in which neurons are connected to specific partners. The construction of the network requires directed growth of axons towards their appropriate targets during development and during neuronal regeneration after a lesion. Axons must navigate through a complex environment where they are guided by a combination of attractive and repulsive molecules. Cellular second messengers, particularly calcium and cyclic nucleotides – cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) – are critical for responses to guidance molecules and axonal pathfinding. Recently, the temporal structure of calcium signals has been shown to have a key role in regulating growth cone behaviors, but the temporal components of cAMP and cGMP signals are largely unknown. The present project proposes to investigate the involvement of second messengers during the midline crossing of spinal commissural axons in vivo. We will first identify the crucial second messengers for the guidance of those axons in the Xenopus spinal cord in vivo. Second, we will use newly improved cyclic nucleotide FRET probes and fluorescent calcium sensors to determine the temporal dynamics of cAMP, cGMP and calcium signaling (the frequency of transients and sustained variations in their intracellular concentrations) in vivo in the growth cones of spinal commissural interneurons. We will then investigate the respective roles of temporally restricted and sustained variations of second messengers in the guidance of commissural axons in vivo, by imposing different frequencies of transient or sustained perturbations of cAMP, cGMP and calcium. Finally, we will investigate the interdependence of these signaling pathways by imaging one second messengers while manipulating another. These studies will substantially advance our understanding of signaling necessary for axonal pathfinding by spinal cord neurons.

Keywords: developmental biology,neurobiology,axon guidance,commissural axons,spinal cord,camp,cgmp,calcium,fret,in vivo imaging
Sources of cosmic rays and gamma ray emission from the Galaxy. (DIFFUSEGAMMAEMISSION)

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: Germany
Call:  (FP7-PEOPLE-2007-2-1-IEF, 2007)
Start date: 2008-06-01
End date: 2010-05-31
Duration (months): 24.0
Total project cost (EUR): 150529.9
EU funding (EUR): 150529.9
Participants: 1
Project status: CLOSED

One hundred years after their discovery by the Austrian physicist Victor Hess, the origin of cosmic rays is still unclear. The detection of TeV gamma rays from supernova remnants (SNRs) by the experiment HESS has strengthened the hypothesis that primary Galactic cosmic-ray electrons are accelerated in SNRs up to the knee energy, where the power-law cosmic ray spectrum changes. Despite this extraordinary recent discovery the question of the origin of cosmic rays is still open, and even if the SNRs prove to be sources of cosmic ray electrons, no compelling evidence for the acceleration of hadrons in SNRs has until now been found. The diffuse gamma radiation arising from the interaction of cosmic-ray particles with matter and radiation in the Galaxy is one of the few probes available to study the origin of cosmic rays. Nevertheless the predictions of the gamma ray flux based upon the measured Galactic matter density and the cosmic-ray spectrum and intensity measured at Earth are in disagreement with the measurements obtained by the EGRET and Milagro detectors. The proposed project aims to investigate the features of the gamma ray spectrum from each direction of the Galaxy and to compare the gamma ray data with the ISM data and use the results as a probe of the cosmic ray flux in the different regions of the galaxy. The regions where the galactic gamma ray flux cannot be explained by interactions of a cosmic ray flux similar to that measured close to the Sun with the passive ISM targets, will be interesting probes of the sites of CR injection.

Keywords: physical sciences,galactic gamma ray astronomy
TCF4 transcriptional program in crypt stem cells and resulting differentiated cells (GUT GENE REGULATION)

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: Netherlands,Netherlands
Call:  (FP7-PEOPLE-2007-4-2-IIF, 2007)
Start date: 2008-03-01
End date: 2010-02-28
Duration (months): 24.0
Total project cost (EUR): 227373.86
EU funding (EUR): 227373.86
Participants: 2
Project status: CLOSED

The Wnt pathway is a key regulatory pathway in development and carcinogenesis. Many of the components of the pathway connecting Wnt to the transcription factor TCF4 have been identified. However, our knowledge of the regulation of TCF4 promoter and enhancer elements in response to the Wnt signal, resulting in development from a stem cell to a differentiated cell, is limited. Largely due to technical constrains it has not been possible to identify TCF4 bound DNA enhancer elements or protein complexes associated with them which dictate specificity of the Wnt signal in the developing tissue. The mouse intestinal epithelium is a rapidly renewing tissue under the control of the canonical Wnt pathway, and therefore ideal to study the above mentioned questions. The proposed project combines state of the art ChIP on chip Genome wide Agilent DNA arrays, Mass Spectrometry, Flow Cytometry, as well as conventional Biochemistry and Molecular Biology to examine Wnt/TCF4 controlled intestinal development in mice. Using these techniques I will identify distal TCF4 regulatory elements, the associated promoters and the protein complexes responsible. Study of the associated complexes and epigenetic marks will help to identify mechanism of activation and repression of the Wnt pathway resulting in the differentiation from a stem cell to a differentiated cell. Stem cells and their development or the misregulation resulting in tumor growth are of major interest to the academic as well pharmaceutical world for their potential use in treatment (stem cells) or the need for a cure (cancer). Therefore it is important to understand how these processes are regulated in vivo. Research in this ever expanding field is very important to maintain Europe’s scientific excellence in the future.

Keywords: tcf4,stem cell,differentiation,intestine
Biopolymer-Based Nanoparticle “Smart” Drug Delivery Systems and their Biopharmaceutical Application by Oral Administration (BIONANOSMART_DDS)

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-2007-4-2-IIF, 2007)
Start date: 2008-10-01
End date: 2010-09-30
Duration (months): 24.0
Total project cost (EUR): 216049.07
EU funding (EUR): 216049.07
Participants: 1
Project status: CLOSED

This initiative aims to gain both fundamental understanding and applied knowledge on novel polysaccharide-based nanoparticles to be utilized as ‘smart’ advanced delivery systems of therapeutic biomacromolecules for oral administration. To this end, nanoparticles will be harnessed from chitosan and other polyionic polysaccharides of biomedical use, cross-linked with a natural non-toxic biocompatible agent. Sensitivity to changes in temperature and pH will be conferred by modifying the surface charge (zeta potential) by modifying the local hydrophilic/hydrophobic balance the nanoparticle surface. While sensitivity towards two biomolecules of therapeutic significance will be achieved by modifying the nanoparticle surface by molecular imprinting, using a non-covalent approach. Phase transitions in these systems will be investigated by means of biophysical techniques including dynamic light scattering and SAXS (small-angle X-ray scattering). The adsorption capacity and selectivity of the molecularly imprinted surface will be studied by quartz crystal micro balance with dissipation mode (QCM-D) techniques. The in vitro release profile will be evaluated as a function of the presence of the external stimuli (temperature, pH and concentration of specific molecules). Citotoxicity and cell uptake will be evaluated in Caco-2 cell monoculture and the biopharmaceutical performance will be evaluated for selected prototypes after oral administration in a rat model.the biopharmaceutical performance will be evaluated after oral administration in a rat model.

Keywords: biopolymer,polysaccharide,'smart' nanoparticles,drug delivery,chitosan,alginate,genipin,hyaluronic acid,molecular imprinting,insulin,d-glucose,oral administration
Quantitative Genetics of Caste in Social Insects (GENETICS OF CASTE)

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: Denmark
Call:  (FP7-PEOPLE-2007-4-2-IIF, 2007)
Start date: 2008-09-01
End date: 2010-08-31
Duration (months): 24.0
Total project cost (EUR): 212823.92
EU funding (EUR): 212823.92
Participants: 1
Project status: CLOSED

The social insects are established model systems for the study of social evolution and are emerging model systems for studying the evolution of behaviour, aging, and complex social phenotypes. However, we know very little of the genetic basis of social insect phenotypes. This is a major limitation because the genetic architecture underlying traits determines how traits respond to selection. The purpose of the proposed research is to develop and implement novel approaches to study the evolution of social insect phenotypes. The two main research objectives are to compare the genetic architecture of two fungus growing ant species that differ in social complexity and to use artificial selection to study how different components of pharaoh ant phenotypes independently respond to selection. While Europe has emerged as a centre of social insect research, it has lagged behind the United States in the field of quantitative genetics, the study of the genetic basis of phenotypes. The researcher (Dr. Linksvayer) has been trained in quantitative genetics at leading institutions in the United States and has pioneered the application of quantitative genetic approaches to social insect systems. The host institution, the Centre for Social Evolution at the University of Copenhagen, is a leading European institution for the study of social insect evolution and has unique facilities, personnel, and experience with the two proposed study systems; the host (Prof. Boomsma) is one of the leading scholars in the field. The proposed research is an ideal match of the unique attributes of the host institution and researcher, and thus provides a perfect opportunity for the transfer of knowledge between Europe and the United States. The study of the genetic and molecular bases of traits is rapidly expanding, and the proposed research will strongly contribute to the establishment of European excellence and competitiveness in this field.

Keywords: evolutionary biology,social evolution,quantitative genetics,entomology
Toward Biodiversity Conservation, Sustainable Use and Benefit-Sharing in Latin America and the Caribbean. (BIOLAC)

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: Italy
Call:  (FP7-PEOPLE-2007-4-2-IIF, 2007)
Start date: 2008-11-01
End date: 2010-10-31
Duration (months): 24.0
Total project cost (EUR): 154821.03
EU funding (EUR): 154821.03
Participants: 1
Project status: CLOSED

A key component of the Millennium Ecosystem Assessment is continued global biodiversity loss and the implications of this for human well being. Biodiversity is a complex resource that demands a multi-disciplinary ecological and economic approach. Solutions to biodiversity loss will come both from better biological models and from a better understanding of the socio-economic factors that benefit from biodiversity, negatively impact its losses and can be directed to sustainable use by appropriate public policies. The continued biodiversity loss of the Latin American and Caribbean (LAC) region is seen as one of the world’s principal environmental problems, with a regional approach to biodiversity yet to be adopted. The role of biodiversity in the provision of ecosystem goods and services to the stakeholders of the LAC, the integration of biodiversity into the region’s peculiar economic structures, the development of economic incentives and payment mechanisms towards regional biodiversity conservation, sustainable use and benefit-sharing, and the production of a generic template for integrated ecological-economic stakeholder-based biodiversity research in the region are the primary objectives of this proposal. These objectives will be achieved through the execution of 5 Modules and 12 associated Work Packages over a 24 month period. Module 1 develops the conceptual framework for the ecological-economic BIOLAC model. Module 2 applies this framework to a selected regional case study. Module 3 calculates the welfare losses at stakeholder levels of biodiversity loss. Module 4 develops payment mechanisms for ecosystem services at a regional level. Module 5 develops a generic framework for the application of the BIOLAC model to other case studies of the region. Each Work Package is sanctioned by deliverables that mark the project’s progress. Dissemination of the project’s methods and results to regional stakeholders and decision-makers is the critical, final deliverable.

Keywords: natural resource economics,environmental policies (environmental protection),ecological economics,resource studies,biodiversity,sustainable exploitation,causes and mechanisms of loss
Small Molecule Antagonists of chromatin modifying enzymes for Regulation of Transcription, proliferation and differentiation (SMART)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Outgoing Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Austria
Call:  (FP7-PEOPLE-2007-4-1-IOF, 2007)
Start date: 2008-08-01
End date: 2011-07-31
Duration (months): 36.0
Total project cost (EUR): 229666.39
EU funding (EUR): 229666.39
Participants: 1
Project status: CLOSED

Chromatin modifying enzymes play important roles in the regulation of gene expression, the establishment and maintenance of distinct cell types during development and the control of cellular proliferation. All of these features make them interesting targets for small molecule inhibitors that can function as probes for basic biological questions but also as lead compounds for drug development. Indeed the first compounds inhibiting histone deacetylases and DNA methyltransferases have been approved for treatment of proliferative disorders. For other equally important classes of chromatin modifying enzymes, in particular histone methyltransferases (HMTases) and histone demethylases (HDMs), currently only few or no small molecule antagonists are available. Here we propose to identify and generate such compounds and test them together with RNAi libraries for their ability to control cell fate decisions and proliferation in two important medical areas, diabetes and cancer. In diabetes therapy, reestablishment of pancreatic beta cell mass is an important clinical goal. We will address the contribution of chromatin modifying enzymes to beta cell proliferation and trans(differentiation) into beta cells, and then use this knowledge to generate and improve small molecules targeting these pathways. While inducers of proliferation are desirable for beta cell expansion, proliferation control is essential for treatment of cancer. Different chromatin modifying enzymes have been implicated as tumor suppressor genes and oncogenes, making compounds targeting these enzymes promising for cancer therapy. We will identify inhibitors of proliferation in several cancer cell lines that show increased expression of chromatin modifying enzymes. Furthermore, the genetic and epigenetic contributions to cancer development and the synergism between signaling and chromatin modification pathways will be addressed in leukemia cells overexpressing Bcr-Abl.

Keywords: oncology,diabetology,cell biology,molecular biology,biochemistry,enzimology
Solid state NMR study of small multidrug resistance proteins (SMRSSNMR)

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: Germany
Call:  (FP7-PEOPLE-2007-2-1-IEF, 2007)
Start date: 2008-09-01
End date: 2010-08-31
Duration (months): 24.0
Total project cost (EUR): 166982.27
EU funding (EUR): 166982.27
Participants: 1
Project status: CLOSED

Small multidrug resistance proteins (SMR) were proven to be one of the responsible factors for drug resistance of bacteria, which represents an actual and serious problem in the therapy of several infectious diseases. Despite of the recent extensive biochemical investigations of SMR proteins the mechanism of substrate recognition and translocation is not yet clearly understood. The aim of the proposed project is the investigation of substrate-protein interaction between a selected SMR protein (e.g. EmrE or TBsmr) and various substrates using solid state NMR and complementary biochemical and biophysical methods. This means investigation of the changes in protein structure and dynamics on interaction with the substrate molecule and assessment of the substrate binding sites. The results are expected to gain an insight into the structure and transport mechanism of SMR proteins. Three different technical and methodological aspects are essential for the progress of this project. 1. Expression and isotop labeling of proteins with protocols already available in the host laboratory which can be optimised for the selected protein if necessary. 2. Reconstitution of proteins into lipid vesicles, in order to obtain the protein as close to its naturally active form as possible and in sufficiently high concentration. 3. Study of substrate-protein interaction with different MAS NMR methods and complementary techniques (if necessary) such as fluorescence spectroscopy. On the last few month of the fellowship first experiments will start on a selected zinc transporter protein (expression and reconstitution), which will be continued after the return of the applicant to the home university in Szeged, Hungary. The project will provide the applicant with training in expression and handling of membrane proteins and in solid state NMR. The aquired skills and knowledge will help the applicant to resume her research career after a break and in obtaining a permanent university position.

Keywords: multidrug transporters,drug resistance,solid state nmr,protein overexpression,cell free expression,isotop labelling,protein reconstitution
Molecular analysis of single-strand break repair (SSBR) in human cells (SSB REPAIR)

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-2007-2-1-IEF, 2007)
Start date: 2008-07-01
End date: 2010-06-30
Duration (months): 24.0
Total project cost (EUR): 178307.05
EU funding (EUR): 178307.05
Participants: 1
Project status: CLOSED

DNA single-strand breaks (SSBs) can arise directly by the action of free radicalsor indirectly as intermediates of base excision repair or topoisomerase I activity. Moreover, replication can convert a SSB into a double-strand break (DSB), one of the most severe DNA lesions that can occur in living cells. Single-strand break repair (SSBR) is therefore crucial to ensure cell survival and the maintenance of genome stability. In addition, SSBR defects have been associated with some neurodegenerative diseases.The main goal of this project is to study the molecular mechanism/s of SSBR in human cells. Our primary focus will be to develop a novel system to induce a site-specific SSB in human cells. This will allow, for the first time, direct analysis of the assembly/disassembly of protein complexes at the SSB reaction by ChIP analyses, in addition to measuring the repair event itself. For example, we will examine the sequence of recruitment of the individual SSBR proteins, as well as identifying which proteins are required for assembly/disassembly/remodelling of protein complexes at chromosomal SSBs. This approach will also provide a system to examine possible SSBR defects in neurodegenerative diseases. We are particullary interested in defining the molecular role of APLF (aprataxin and PNK like factor), a SSBR protein recently identified in this laboratory.

Keywords: health sciences,molecular biology,mammalian cell biology,single-strand break repair,genome stability,neurodegenerative disease