
UNIVERSITE TOULOUSE III [PAUL SABATIER]
UNIVERSITE TOULOUSE III [PAUL SABATIER]
227 Projects, page 1 of 46
assignment_turned_in ProjectFrom 2011Partners:UNIVERSITE TOULOUSE III [PAUL SABATIER]UNIVERSITE TOULOUSE III [PAUL SABATIER]Funder: French National Research Agency (ANR) Project Code: ANR-11-BSV2-0015Funder Contribution: 500,000 EURThe last decade has been marked by the deciphering of whole genome sequence in numerous species. Recent advances in transcriptomics further reveal that an unexpectedly large proportion of our genome produces atypical RNAs that, unlike mRNAs, do not encode proteins. From seminal works in nematodes, it is well now established that short non-coding RNAs (ncRNA), including microRNAs, play key roles in the control of development and differentiation. In addition, experimental cases show that large (>1kb) non-coding RNAs can contribute as well to various regulatory functions in the control of gene expression. The role and mode of action of large RNAs that do not encode proteins remains however poorly understood. Therefore, a major challenge resides in understanding the molecular and developmental functions of this novel class of RNAs. Most large RNAs nevertheless comprise small Open-Reading-Frames (smORF) that, precisely because of their small size, are generally considered as being non-functional and filtered off from annotations. However, at least some of these smORF may encode peptides, the abundance of which is probably underestimated. We have recently discovered that the Polished-rice (Pri) small peptides (11-32aa) encoded by an alleged “ncRNA” play a critical role in the control of transcriptional programs during the Drosophila development. These atypical small peptides therefore represent the first case of a novel regulatory mechanism. Several evidence support that small peptides encoded by apparently ncRNA fulfill additional roles in regulating development and differentiation, but their abundance, functional repertoire and mode of action remains entirely to be elucidated. We aim to address these questions by a combination of large scale functional and bio-informatics approaches in Drosophila. Our team is a recognized leader in the study of epidermal differentiation during Drosophila embryogenesis, as a paradigm of cell morphogenesis. Previous works have established the importance of the Shavenbaby Transcription Factor that determines, in a robust manner, the precise subset of epidermal cells forming apical extensions, referred to as trichomes. Consistently, independent modifications of Svb expression have caused diversification of trichome patterns throughout the evolution of insects. Shavenbaby directly activates the transcription of various cell effectors, collectively responsible for trichome cell morphogenesis. We have recently found that the transcriptional activity of the Svb protein is controlled by Polished-rice small peptides. During embryogenesis, Pri trigger the N-terminal truncation of the Svb protein, switching its activity from a (full length) Repressor an (truncated) Activator. Importantly, we obtained suitable conditions to transfer this functional interaction between Pri peptides and the Svb Transcription Factor in stable cell lines, providing a unique opportunity to explore the molecular mechanisms underlying this novel aspect of the control of genome expression. Based on accumulated biological tools and a collaborative network with international specialists, this research program aims at unraveling how small peptides control multiple steps of the Drosophila development. Our specific goals are to: 1) provide compelling insights into the molecular determinants and cellular factors mediating Pri peptides activity on the truncation of the Svb transcription factor, 2) identify additional cellular functions and the corresponding regulators that are targeted by Pri peptides during Drosophila development, 3) use Pri as a paradigm to explore the repertoire of small peptides putatively encoded by similar apparently non-coding RNAs.
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For further information contact us at helpdesk@openaire.euassignment_turned_in ProjectFrom 2011Partners:UNIVERSITE TOULOUSE III [PAUL SABATIER]UNIVERSITE TOULOUSE III [PAUL SABATIER]Funder: French National Research Agency (ANR) Project Code: ANR-11-BSV2-0008Funder Contribution: 481,424 EURResident stem cells in adult organs play an essential role in tissue homeostasis. The tissue environment (niche) in which stem/progenitor cells reside plays a decisive role in providing the structural, trophic support and appropriate signals to regulate stem cell function. Genetic and molecular studies in mice have uncovered many signalling pathways involved in the communication between HSCs and their niche. However, our knowledge of the haematopoietic niche plasticity and function remain very fragmentary. Discovery, including by us, of a Drosophila haematopoietic niche, termed PSC, in the larval hematopoietic organ (the lymph gland, LG), has opened the prospect of using this model organism to decipher the basic rules of haematopoiesis and haematopoietic niche function. The PSC is a genetically tractable model to study how different signalling pathways and gene regulatory networks are integrated for maintenance of multipotent progenitors, with developmental and evolutionary perspectives. Not surprisingly, the number of excellent European and non-European laboratories studying Drosophila haematopoiesis has rapidly increased during the last few years. We need to face this intense competition in order to keep a leadership position. Our previous work has shown that Collier, the Drosophila ortholog of mammalian Early B-Cell Factor (EBF) specifies the PSC. We then showed that PSC cells act, in a non cell autonomous manner, to maintain JAK/STAT signalling in pro-hemocytes, thereby preventing their premature differentiation and preserving their multipotent character. It revealed that haemocyte homeostasis is dependent upon interactions between haematopoietic progenitors and their micro-environment in Drosophila, as is the case in vertebrates. Our most recent data (ANR prodrohemo) identified a new mode of regulation of JAK/STAT signalling in pro-hemocytes, an unexpected heterogeneity of these progenitors and the key role of Dpp/BMP signalling in maintaining the PSC size. BMP signalling was previously shown to control the number of osteoblasts, a major component of the HSC niche in the mammalian bone marrow; very recently EBF2 was shown to be required in immature osteoblasts. The striking parallels between the Drosophila PSC and the mammalian HSC niche raise fascinating questions. Our project has three main objectives: A molecular dissection of the PSC maintenance and function in physiological and parasitism conditions. A molecular characterisation of pro-haermocytes and the role of JAK/SAT signalling. A global, integrated view of the reciprocal communications between the PSC and pro-haemocytes. Methodology: Our project will take advantage of the combination of the Drosophila genetic and genomic resources, including dsRNA lines for gene extinction, imaging with new fluorescent reporter proteins, and novel methodologies : Laser micro-dissection of the LG cells and RNA TU-Tagging, followed by high-throughput RNA sequencing will allow to determine with unprecedented precision the molecular signatures of PSC cells and pro-haemocytes in wt larvae, mutant contexts and following parasitism; systematic integration of vertebrate and Drosophila datasets will be performed through external collaborations. Conclusion Deciphering molecular networks involved in maintaining a functional niche and characterizing, at the molecular level, cellular communications involved in the control of Drosophila haematopoiesis should provide important new knowledge on a primary aspect of innate immunity, the control of quiescence/proliferation of haematopoietic progenitors in physiological conditions and in response to immune threats. Together with ongoing studies on the role of EBF2 and various signaling pathways involved in the communications between osteoblasts and HSCs in vertebrates, our new research program should shed novel light on the emergence and diversification of haematopoietic microenvironments during evolution.
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For further information contact us at helpdesk@openaire.euassignment_turned_in ProjectFrom 2007Partners:UNIVERSITE TOULOUSE III [PAUL SABATIER]UNIVERSITE TOULOUSE III [PAUL SABATIER]Funder: French National Research Agency (ANR) Project Code: ANR-07-JCJC-0007Funder Contribution: 90,000 EUR1- Scientific background and objectives The goal of data assimilation is to combine optimally various sources of data, typically a model and observations, to estimate the state of a physical system. One of the main drawbacks of sequential data assimilation methods, such as the Kalman filter, is that they only use the direct model, and hence cannot anticipate the future evolution of the system to improve its estimation at a given time. The goal of this project is to study a method aimed at bypassing this limitation, and in which the assimilation process alternates between the direct and backward models. Such a method will have in particular the main advantage of a very simple numerical implementation, whereas the human implementation cost needed by the current data assimilation methods is increasingly growing. 2- Description of the project, methodology The first aspect of the project is to establish the properties and conditions for convergence of the system. The backward model is in general unstable (as illustrated by the diffusion equation), but thanks to assimilation, the observations can be used to constrain the backward model within a realistic range. It has already been proved (both theoretically and numerically) on a toy model (simplified oceanic model, large network of observations, degraded Kalman filter) that the backward model can be stabilized by adding a constraint that forces the data assimilation back to the observations. It remains necessary to extend this preliminary result to a more realistic case (primitive equations model, incomplete observations, SEEK filter). This step will be carried out by replacing the problem of data assimilation and BFN algorithm into the more general framework of the observation problem for dynamical systems developed the last fifty years in the automatic and control theory field. In these two domains, the observation and filtering problems are closely linked, and the recent development of nonlinear filters and observers provides an additional theoretical basis to this project, as it has recently allowed us to prove some theoretical convergence results on simple nonlinear EDO systems. The second aspect is to continue the numerical tests for simple models (Burgers equation, or baroclinic quasi-geostrophic ocean model), and with a simplified sequential assimilation method: Newtonian relaxation from the model to the observations (nudging). It will then be compared with the two classical assimilation methods (4D-Var and Kalman filter) in several twin experiments (the observations are extracted from the model runs, and the time and spatial distributions can be set arbitrarily) in which the observation network will be more and more sparse, which make it harder to control the backward model. Statistical interpolation and the Kalman filter, which are more sophisticated than simple nudging, will be tested in order to possibly address the deficiencies of nudging and improve assimilation. This numerical validation will be jointly carried out with the theoretical aspect mentioned in the previous paragraph. We will study at the same time the effect of the presence of data and/or model errors in the identification process. The third aspect is to implement the method for a general oceanic circulation model (OPA). This will be done in twin experiments, first with a complete observation network, then in the partial case; and first using nudging, then using the Kalman filter developped at LEGI (SEEK filter). Finally, the implementation will be carried out with real data. The results will be compared to those of 4D-Var and standard SEEK. It is also clear that this will be jointly carried out with the theoretical study of back and forth algorithms applied to oceanic circulation models. 3- Expected results The long-term objectives are on one hand to obtain convergence results for the various existing direct and backward methods, and compare this new class of algorithms to classical assimilation methods on the OPA model, the goal being to identify the real trajectory of the system at least as accurately and as efficiently as those methods. By obtaining theoretical results of convergence (possibly in simplified cases) and especially by the numerical validation with real sets of observations, it will be possible to achieve the development of this new class of data assimilation algorithms. The numerical validation should confirm the preliminary results of quite good identification of the model/data errors. This will provide to the oceanographic (and more generally geosciences) community an alternative class of realistic data assimilation algorithms, with a very simple implementation.
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For further information contact us at helpdesk@openaire.euassignment_turned_in ProjectPartners:UNIVERSITE TOULOUSE III [PAUL SABATIER]UNIVERSITE TOULOUSE III [PAUL SABATIER]Funder: French National Research Agency (ANR) Project Code: ANR-11-JS04-0008Funder Contribution: 195,560 EURThe CAPhyP project aims at developing and optimizing a novel apparatus to measure very small optical anisotropies, and more precisely directional anisotropies. Based on a very high finesse ring cavity, it is inspired by modern techniques from frequency metrology to reach, in its preliminary version which is still rather basic, a sensitivity on the order of 10^-18, which is already approaching the state-of-the-art values. Our first results, combined with recent ones from other groups, make us confident that once it is optimized, our apparatus should be sensitive enough to test for example the predictions of QED in quantum vacuum or some fundamental symmetries of physics, such as Lorentz invariance. While developing and improving the experiment, we will measure its progress by studying in gases two magneto-electro-optical effects that exist in all media, in the presence of transverse magnetic and electric fields, either parallel or crossed: the Jones birefringence, with eigenaxes rotated by +/-45° with respect with the applied parallel fields, and the directional anisotropy, corresponding to the fact that the velocity of light propagating orthogonally to the applied crossed fields is not the same in both directions. Predicted about 30 years ago, these two magneto-electro-optical effects have been first observed in 2002 in dense media. Thanks to our apparatus which final sensitivity will improve the state of the art by about 2 orders of magnitude, a few months ago we were able to observe for the first time that in the presence of transverse and orthogonal electric and magnetic fields, light does not propagate with the same velocity in both directions, even in gases without any intrinsic anisotropy! The studies that we plan in the project will provide us with previously inaccessible experimental data, in order to deepen the understanding of the light-matter interaction beyond the electric dipole approximation. Besides, the directional anisotropy in solids is presently studied by several groups in view of practical applications such as magnetically controlled non reciprocal retardation plates. With only slight changes, our apparatus will also allow us to explore this phenomenon in dense media.
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For further information contact us at helpdesk@openaire.euassignment_turned_in ProjectFrom 2007Partners:UNIVERSITE TOULOUSE III [PAUL SABATIER]UNIVERSITE TOULOUSE III [PAUL SABATIER]Funder: French National Research Agency (ANR) Project Code: ANR-07-JCJC-0009Funder Contribution: 148,300 EURA key question in the formation and evolution of galaxies is the epoch and mechanisms of mass assembly. Proging the dynamics, and hence the gravitational mass, of high-redshift galaxies is crucial for this purpose but is limited, up to now, to a few limited-size samples. We propose in this project to measure the velocity field of a large sample of star-forming galaxies in the redshift range 1.0
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