COMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAY
COMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAY
17 Projects, page 1 of 4
assignment_turned_in ProjectFrom 2009Partners:COMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAY, LETICOMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAY,LETIFunder: French National Research Agency (ANR) Project Code: ANR-08-PCVI-0009Funder Contribution: 250,000 EURRecent technological advances, such as high magnetic field MR imaging systems, high magnetic field gradient coils and specialized radiofrequency detectors brought the imaging of single biological cells within reach. The application of Magnetic Resonance Imaging (MRI) to the study of small biological systems, in particular single biological cells, requires the acquisition of images not only with very high spatial resolution and but also with adequate contrast to noise ratio. The overall goal of the work proposed here is to develop MR imaging techniques for use in ultra high field MRI systems. In particular, we propose to implement the diffusion enhancement of signal and resolution ("DESIRE") technique, a diffusion based technique which has the potential of highly increasing the contrast in imaging with very high spatial resolution. The DESIRE effect has been demonstrated experimentally in 1 dimension. Here, we propose to implement the DESIRE method in 2, and 3 dimensions. A major portion of this work involves the design and testing of pulse sequences to facilitate the implementation of the technique. In addition, we plan to investigate the contrast associated with diffusion enhanced images and measure diffusion properties in phantoms, single biological cells, and biological tissues at very high magnetic fields.
All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=anr_________::310d07df67fd808877ec0974ee3e17a5&type=result"></script>'); --> </script>
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For further information contact us at helpdesk@openaire.euassignment_turned_in ProjectFrom 2009Partners:COMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAY, LETICOMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAY,LETIFunder: French National Research Agency (ANR) Project Code: ANR-08-BLAN-0327Funder Contribution: 150,000 EURDiffusion-weighted magnetic resonance imaging (DMRI) has become a key tool for investigating the structural organization of the human brain over the past twenty years. First, it has first been used in the clinical context of early detection of acute brain ischemia, but also rapidly provided a way to infer assess anatomical connectivity through the mapping of white matter fiber bundles (see Le Bihan 2003 for a review). It is so far the only technique providing such kind of information in vivo. More recently, the DMRI signal has been shown to reflect brain activity (Le Bihan 2006) and diffusion MRI is becoming another means to look at brain function. Diffusion functional magnetic resonance imaging (DfMRI) seems to reflect more directly the activation process, delivering a peak in the activity earlier than with the classical, hemodynamically driven BOLD (Blood-Oxygen Level Dependant) imaging method. The biological mechanisms underlying this new approach are still debated in the community. Based on extensive literature reports we have hypothesized that some changes in the network structure of cellular water could accompany neuronal activation. In particular two different pools of water molecules have been identified within cells, with a slow diffusing pools which would result from interaction of water molecules with cell membranes (Le Bihan 2007). The purpose of this project is twofold. First we would like to investigate the microstructural changes which occur in brain tissue during activation and correlate them with the observed changes in water diffusion. This part which will be conducted in primates and combine several imaging techniques will provide us with a better characterization of the DfMRI signal in terms of temporal and spatial features. Second, we would like to develop a numerical simulation tool based on an accurate model of the biophysical processes underlying water diffusion in cells and tissues. This tool will give us the opportunity to explain the changes in water diffusion behavior which have been observed in different known physiological (brain activation) or pathological (ischemia) situations and to evaluate assumptions or new conditions which may not be tested in vivo, so as to predict new findings or optimize imaging acquisition parameters. Overall results will be used to optimize DfMRI in human subjects.
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For further information contact us at helpdesk@openaire.euassignment_turned_in ProjectFrom 2009Partners:LETI, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE ILE-DE-FRANCE SECTEUR PARIS B, COMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAYLETI,CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE ILE-DE-FRANCE SECTEUR PARIS B,COMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAYFunder: French National Research Agency (ANR) Project Code: ANR-08-SYSC-0007Funder Contribution: 215,049 EURAll Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=anr_________::40277829fddc7983f65a7869243f1648&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eumore_vert All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=anr_________::40277829fddc7983f65a7869243f1648&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euassignment_turned_in ProjectFrom 2009Partners:LETI, COMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAY, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE ILE-DE-FRANCE SECTEUR SUDLETI,COMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAY,CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE ILE-DE-FRANCE SECTEUR SUDFunder: French National Research Agency (ANR) Project Code: ANR-08-BLAN-0229Funder Contribution: 433,228 EURTranscription is the first step of gene expression. As such, it is essential that organisms tightly regulate this process to ensure that the genetic programs are performed harmoniously and allow the proper synthesis of the components that the cell requires at a given time and in a given developmental situation. In eukaryotes, three RNA polymerases (Pol) transcribe the genome. Pol II is responsible for the transcription of messenger RNAs and many small non-coding RNAs. As such, it has to respond to the large number of situations encountered by the cell and to adapt the level of transcription of tens of thousands of genes. In eukaryotes, hundreds to a couple of thousands of transcription activators, recognizing sequences located in enhancers or upstream activating sequences, trigger the transcription of the adjacent genes. A large protein complex, the Mediator of transcription, also called Mediator for short, is responsible for the recruitment of Pol II in response to the transcription factors and, together with the general transcription factors, for the assembly of preinitiation complex and ultimately transcription initiation. Mediator is constituted of at least 25 subunits that are engaged in numerous contacts within the complex. Mediator also interacts with partners belonging to other components of the transcription machinery, including general transcription factors and co-activators that modify the chromatin, and with other complexes involved in various nuclear processes. Mediator can thus be compared to an antenna, capable of receiving the activation signals through protein-protein interactions with the hundreds of transcription activators of the eukaryotic cell, integrate these signals and activate transcription by triggering the recruitment of Pol II and possibly some of the general transcription factors. While Mediator has been studied intensively, its complexity has precluded a detailed understanding of how it responds to activators in connection with co-activators, of what is its role in preinitiation complex formation and of how it ultimately recruits Pol II in vivo. The general objectives of this proposal are, using Saccharomyces cerevisiae as a model system, (i) to investigate in vivo how the protein-protein interactions within Mediator transmit the activation signals from activators to the GTFs and Pol II; (ii) to identify the subunits of Mediator that directly contact Pol II and investigate the role of these contacts and; (iii) to understand how Mediator and co-activators cooperate to activate transcription and stimulate preinitiation complex formation. The rationale of the project will be to identify which subunits of Mediator interact with Pol II using a new in vivo cross-linking methodology. We will then produce collections of temperature sensitive mutants in essential subunits of Mediator, targeting in particular those that interact with Pol II. The effect of the mutations on the interactions of the subunits with all their known partners will be tested. In parallel, we will look at the effect of the mutations on the expression of specific genes using RT-qPCR or genome-wide using DNA micro-arrays. We expect that some of the mutations will lead to genome-wide defects while other will impair transcription of subsets of the genome only. Incidentally, microrarrays will allow the identification of the genes that are the most strongly affected, facilitating the characterization of the impaired mechanism. We will also investigate the effect of the Mediator mutations on the association of Mediator itself, the co-activators, the general transcription factors and Pol II on specific genes (in particular those of the methionine regulon) or, when needed, genome-wide. In this project, we would like to concentrate at first on five essential Mediator subunits: Med4, Med7, Med8, Med10 and Med21. Med7 and Med8 were chosen because our preliminary cross-linking results suggest that they interact directly with Pol II and could thus play a major role in its recruitment. In summary, this project aims at gaining an integrated view of the mechanisms of transcription activation and at understanding how Mediator performs this central function in gene expression in vivo. We will look at this process from the initial step of the recruitment of Mediator by activators to Pol II recruitment taking advantage of the huge power of yeast genetics, molecular biology and functional genomics. We anticipate that our work might have implications for the understanding of human diseases that are the consequence of altered regulation of gene expression.
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For further information contact us at helpdesk@openaire.euassignment_turned_in ProjectFrom 2008Partners:INRIA, LETI, SNCF, COMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAYINRIA,LETI,SNCF,COMMISSARIAT A LENERGIE ATOMIQUE - CENTRE DETUDES NUCLEAIRES SACLAYFunder: French National Research Agency (ANR) Project Code: ANR-08-SEGI-0009Funder Contribution: 730,324 EURAll Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=anr_________::d53f86d674cd9200703784a6618a8436&type=result"></script>'); --> </script>
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