Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Genetic analysis of olfactory processing and function (ODORPROCESSING)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-07-01
End date: 2015-06-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

I am interested in the neural basis of stimulus-driven behaviors. I propose a combination of molecular genetic, in vivo imaging and behavioral approaches to understand the neural processing of olfactory information in the mouse brain. Smell is an essential sense that allows animals to detect food, predators and mates. Olfactory stimuli are recognized by odorant receptors expressed in sensory neurons in the nose. Individual sensory neurons express one of 1300 receptor genes and neurons expressing a given receptor project to a single synaptic structure, called glomerulus, in the olfactory bulb. The patterns of axonal projections are spatially invariant and provide a topographic map of odorant receptor activation in the brain. Information encoded by glomerular activity is transmitted by olfactory bulb projection neurons to several higher olfactory centers in the cortex. Sensory processing at these higher olfactory centers is thought to link odor representations to appropriate behaviors. Central to understanding olfactory processing is the elucidation of the functional properties of the underlying neural circuits. In an effort to address this fundamental problem in sensory biology, I have altered the patterns of neural activity evoked by odors, by generating transgenic mice in which 95% of all sensory neurons express the same receptor. In vivo imaging and behavioral analyses of these mice suggest a model of olfactory processing in which the recognition of patterns of neural activity, or contrast, is critical for odor detection. To test this model, I will exploit a set of defined genetic perturbations I have created in transgenic mice which alter the expression of odorant receptor genes. I will employ state-of-the-art imaging approaches to reveal how genetically defined patterns of glomerular activity are transformed into higher order odor representations, and I will examine the consequences of such perturbations for innate and learned olfactory-driven behaviors.

Keywords: sensory processing,mouse genetics,olfactory-driven behavior
Molecular mechanisms of transcriptional regulation of lymphocyte development by the E2A splice variants E12 and E47 (SPLICE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-03-01
End date: 2015-06-10
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The E2A gene encodes for two alternatively spliced proteins, namely E12 and E47, which belong to the family of basic helix-loop-helix transcription factors. The E2A proteins have been characterized extensively as regulators during various stages of B and T lymphocyte development. Recently, we have generated mice deficient for either E12 or E47 and examined their roles in B cell maturation. We show that E47 is essential for developmental progression at the pre-pro- B cell stage, while E12 is dispensable for early B cell development, commitment and maintenance. In contrast, both E12 and E47 play critical roles in pre-B and immature B cells to promote Igλ germline transcription as well as Igλ VJ gene rearrangement. However, it is unclear which molecular mechanisms are used by E12 and E47 to drive lymphocyte development. Thus, the goals of this study are to 1. identify the signalling events that control transcription and splicing of the E2A gene, 2. define individual target genes and interaction partners of E12 and E47 and 3. to examine the distinct functions for E12 and E47 during T cell development. These goals will be accomplished using the previously generated mouse models, lacking either the E12 or E47 protein in combination with cellular and molecular biology approaches. Additionally, the first goal will be approached in cooperation with the applicant’s previous lab, since this lab has extensive experience with the proposed state-of-the-art whole genome Chromatin Immunoprecipitation combined with deep sequencing (ChIP-Seq) approach. Overall, this project will contribute to our understanding of the molecular mechanisms of transcriptional regulation as well as lymphocyte development.

Keywords: transcriptional regulation,e2a,e12,e47,alternative splicing,b cell development,t cell development,interleukin-7 signaling,histone modifying enzymes
Dissecting the discrete steps of mitochondrial fusion (MITOFUSION)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-04-01
End date: 2015-03-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Mitochondria are not single isolated organelles but constitute a real network comparable to the Endoplasmic Reticulum or the Golgi apparatus. In wild type conditions, this network adopts a tubular morphology that is conditioned by active and constant processes of fission and fusion of mitochondrial membranes. Unlike other organelles, fusion of mitochondrial membranes is not catalyzed by SNAREs but involves two sets of large GTPases, the mitofusins and OPA/Mgm1, involved in fusion of outer and inner membranes, respectively. Consequently, these GTPases not only participate in transmission of mitochondrial DNA and therefore oxidative phosphorylation but also play a major role in apoptosis. In addition, impairment of mitochondrial fusion is directly linked to several neurodegenerative syndromes such as Parkinson and Charcot-Marie Tooth diseases as well as Dominant Optic Atrophy. The importance of elucidating the mechanism underlying mitochondrial fusion therefore becomes evident. We have previously shown that Fzo1, the yeast mitofusin, is subject to exquisite regulation by the Ubiquitin-Proteasome System. Based on this, we will aim at dissecting the involvement of the ubiquitin-proteasome system in movement, tethering and fusion of outer and inner membranes. To reach this goal, multidisciplinary in vivo and in vitro approaches will be employed, including genetics, biochemistry and cell biology imaging techniques. Besides elucidating molecular mechanisms underlying mitochondrial fusion, the present project is likely to generate concepts that may apply to all membrane fusion events within eukaryotic cells. Contributions to understanding of neuropathies directly caused by defects of mitochondrial dynamics are also to be expected.

Keywords: cell biology,molecular genetics,proteomics,microbiology,molecular biology,molecular biophysics,biochemistry
Extrinsic Geometric Flows on Foliated Manifolds (EGFLOW)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: European Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Israel
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-06-01
End date: 2014-05-31
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

The project investigates the extrinsic geometry of foliations (expressed by the 2nd fundamental form of leaves) using the approach of the geometric flows. We propose to study not just a single foliated manifold (M, F, g), but rather – assuming a suitable local existence theory – a foliation with a one-parameter family of F-truncated metrics gt parametrized by a ‘time’ t. The research objectives are to develop Extrinsic Geometric Flow (EGF) on foliated manifolds recently introduced by the applicant (commonly with P. Walczak, arXiv:1003.1607v1) for codimension-one foliations as a new research tool for studying the extrinsic geometry of foliations. We shall also use the methods of geometric analysis and PDE’s, theory of Riemannian submanifolds, integral formulae for foliations, topology and dynamics of foliations, and computer simulations. The (hoped for) results concern (i) Development of EGF for a foliation of codimension-1 and of arbitrary codimension: existence and uniqueness theorems, converging as , behavior of curvature, singularities, extrinsic geometric solitons (for totally umbilical metrics, foliated surfaces and 3-manifolds), F-truncated variations of related total quantities and geometry of stable critical metrics etc; (ii) Applications of EGF to solutions of various problems (by Gluck-Ziller, Walczak, Toponogov etc) concerning the extrinsic geometry of foliations: minimizing functions like volume and energy defined for plane fields on Riemannian manifolds, the extrinsic Ricci and Newton transformation flows, foliated Riemannian submanifolds, combining integral formulae for real and complex foliations with the approach of EGF etc. The topic belongs to differential geometry and topology, subjects of pure mathematics.

Keywords: riemannian metric,foliation,extrinsic geometric flow,integral formula,mixed curvature,higher mean curvature,hyperbolic pde,soliton solutions,totally umbilical,variation formula
Mechanisms of transport across biological membranes (BIOL-TRANSP-COMPUT)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-04-01
End date: 2015-03-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Living cells depend on the correct functioning of proteins that transport cargo across the membranes. We will use computer simulations to understand the mechanisms employed by three proteins that mediate transport across biological membranes. Each of these three proteins is important for physiology and disease. A large part of the research planned aims at understanding the SecA motor protein. SecA is an essential component of the Sec translocation system in bacteria, where it couples the hydrolysis of adenosine triphosphate (ATP) with remarkable protein conformational changes to transport newly synthesized proteins across the plasma membrane. Key open questions concern the mechanism of the chemical-mechanical coupling employed by SecA, and how SecA works together with the SecYEG protein channel to translocate proteins. We will address these questions by performing molecular dynamics computations at the classical and combined quantum mechanical/molecular mechanical levels, and bioinformatics analyses. The plasma membrane proton pump is a member of the P-type ATPases family, complex enzymes essential for maintaining the plasma membrane potential and for secondary transport systems in eukaryotes. We will assess the dynamics of the AHA2 plasma membrane proton pump in a hydrated lipid membrane, the mechanism of long-distance conformational coupling, and the functional role of specific amino acids. Channelrhodopsin-2 is a light-gated cation channel that can be expressed in mammalian neurons and used as a powerful tool to probe neuronal circuits. Comparison of the sequences of channelrhodopsin-2 and other microbial-type rhodopsins raises intriguing questions about the functional roles of specific amino acids. To contribute to the general understanding of the principles that govern the design of membrane transporters, we will combine homology modeling of channelrhodopsin-2 with molecular dynamics of channelrhodopsin-2, bacteriorhodopsin, and sensory rhodopsin.

Keywords: natural sciences,protein secretion,proton pump,proton channel,protein dynamics,protein:lipid interactions,molecular dyanamics,combined quantum mechanics/molecular mechanics computations
Elucidating mechanisms of dopaminergic neuronal degeneration using C. elegans and high-throughput genetic approaches (NEURODOPA DEGEN)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Norway
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-07-01
End date: 2014-06-30
Duration (months): 36.0
Total project cost (EUR): 75000.0
EU funding (EUR): 75000.0
Participants: 1
Project status: CLOSED

BACKGROUND: Parkinson’s Disease, characterized by the progressive degeneration of dopaminergic neurons, afflicts millions of people. Yet, no effective therapeutic strategies are available. This work uses Caenorhabditis elegans to study dopaminergic degeneration. C. elegans is a small nematode, highly amenable to genetics and high-throughput approaches, with a simple nervous system that is highly conserved at the level of gene expression and pathology with humans. This study also utilizes a mutant in a Transient Receptor Potential (TRP) channel, trp-4(d), in which dopaminergic neurons properly specify but later on progressively degenerate. OBJECTIVES: 1. Understand the molecular mechanisms of dopaminergic neurodegeneration 2. Identify potential therapeutic targets 3. Uncover novel causes of neuronal cell death STRATEGIES: 1. Using a candidate approach I will investigate which of the known cell death pathways (apoptosis, autophagy, necrosis) mediate trp-4(d) dopaminergic degeneration. 2: I will perform a suppressor screen on trp-4(d) mutants to identify genes that can stop dopaminergic cell death. High-throughput genetic approaches (automated screening and Whole Genome Sequencing) will be employed for mutant isolation and identification. Characterization of the retrieved genes will elucidate molecular mechanisms that can block dopaminergic degeneration. 3. It is conceivable that more genes exist that when mutated have, like trp-4(d), detrimental effect to the survival of DA neurons. I will take an unbiased high-throughput forward genetic screening approach designed to selectively isolate dopaminergic degeneration mutants to reveal novel causes of neuronal cell death. RELEVANCE:The expected outcomes are of high medical significance and relevance to human neurodegenerative conditions. The proposed work, employing state of the art methodology, will not only enhance European competitiveness in disease related research but also contribute to its technological excellence.

Keywords: neurobiology,laboratory animal science,neuronal degeneration,dopaminergic neurons,transient receptor potential (trp) channels,forward genetic screen,high throughput,c. elegans
RTP801, A NEGATIVE REGULATOR OF mTOR AND AKT, AS A TARGET OF PARKIN (RTP801 PARKIN)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-04-01
End date: 2015-03-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

In this proposal, we hypothesize that RTP801, a neuron-death associated protein, is a target for parkin in cellular and animal models of Parkinson's disease (PD). We will test whether parkin regulates the proteasomal degradation of RTP801 and whether parkin loss of function elevates RTP801 to mediate neuron death in cellular and animal models of PD. RTP801 is elevated in cell and animal models of PD and in affected neurons of PD patients. In PD models, RTP801 up regulation leads to inactivation of mTOR and Akt, and therefore neuron death. Parkin is a PD-associated gene that, when mutated, triggers juvenile recessive-autosomal forms of PD. Controversially, mutations in only one allele of parkin gene can be a risk factor for Parkinsonism. Our preliminary results suggest that RTP801 is degraded by the ubiquitin proteasome system and that parkin impairment leads to RTP801 accumulation in vitro. We will investigate whether parkin loss of function triggers toxic accumulation of RTP801 at a transcriptional level and/or at the protein level, due to degradation impairment. We will analyze the toxicity of different parkin mutations and if so, whether they induce cell death through RTP801. In this context, we will also investigate whether the mTOR /Akt survival pathway is impaired. Moreover we will investigate whether mutant Parkin -Q311X mice show RTP801 accumulation in the Substantia Nigra (SN). Finally, and if available, we will explore the levels of RTP801 in human tissue from patients with several parkin mutations to see if the samples exhibit elevated levels of RTP801 in the affected neuromelanin neurons in the SN. The final goal of these experiments will be a better understanding of neural degeneration in the disease and will help to design effective therapeutic approaches to treat neural degeneration in PD.

Keywords: health sciences,neurosciences,neurobiology,neurochemistry,neurology,parkinsons's disease,mtor,parkin,rtp801/redd1,neuron cell death,apoptosis
Understanding the roles of mammalian sialidases in glycolipid catabolism (CATABOLIC SIALIDASES)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Türkiye
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-04-01
End date: 2015-03-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Sialidases are widely distributed in nature, from microorganisms to mammals. Mammalian sialidases differ in their tissue distribution, subcellular localization, substrate specificity and pH optimum. To date, several mammalian sialidases have been cloned; a lysosomal form (Neu1), a cytosolic form (Neu2), a plasma membrane-associated form (Neu3) and a lysosomal/mitochondrial form (Neu4). Defining the functional impact of sialidases on complex physiological and cellular processes should uncover the biological significance of sialidase-susceptible sialic acids on glycoproteins and glycolipids. Our goal has been to clarify biological functions of mammalian sialidases. Recently we investigated the role of lysosomal/mitochondrial sialidase Neu4 in glycolipid degradation using mouse model with the combined deficiency of β-hexosaminidase A (HexA) and sialidase Neu4. Our mouse model progressed toward the neuropathological abnormalities of human Tay-Sachs patients. The appearance of epileptic seizures and increased glycolipid storage demonstrated the predicted increased severity of disease indicative of the importance of Neu4 in glycolipid degradation but it is clear from the much milder than expected phenotype that other sialidases such as Neu1 and Neu3 also contribute to catabolism reactions. We now propose to investigate the intralysosomal mechanism by which glycolipids are degraded by sialidase Neu1 using mouse models. Therefore, the main objectives of this proposal are: (1) to generate first Neu1-/- knockout mouse models (2) to generate Neu1-/-HexA-/- (3) to generate Neu1-/-Neu4-/-HexA-/- triple knockout mouse models. If successful, our studies will significantly increase the state of knowledge of sialidase contribution in glycolipid degradation and can suggest new therapeutic approaches for Tay-Sachs disease based on the Neu1 and Neu4-catalyzed metabolic bypath.

Keywords: sialidase,glycolipid,mouse model,tay-sachs disease
BIODIVERSITY AND ECOSYSTEM FUNCTIONING: individual-based modelling to understand and predict the consequences of biological invasions (INVABIOECOF)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: European Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2012-02-01
End date: 2015-01-31
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

Human activities and global changes are increasingly impacting biodiversity and the functioning of ecosystems. The ability of ecologists to determine how threatened communities and ecosystems will respond to these changes is crucial for conservation management and the setting of European environmental policy. Yet, our ability to determine how ecosystems may respond to such changes is limited, despite ecologists frequently being requested to provide policy makers with predictions. The aim of the project is to understand how non-random alteration of biodiversity by perturbations may affect ecosystem functioning, using invasive top-predatory fish as a non-random perturbation. Given their crucial role in food-webs and their high economical and social value, they are excellent candidates to investigate this question. The specific objectives are to use individual-based modelling to investigate some hypotheses related to biodiversity and ecosystem functioning and generate empirically testable predictions. After testing these predictions, the model will used to determine the consequences of scenarios of biological invasions. To achieve these objectives, model simulations, field investigations and experimentations in small lakes will be conducted. Data collection will be based on an innovative approach utilising state-of-the-art techniques (individual tagging, telemetry and stable isotope analyses). To maximize the opportunity for successful completion, the Fellowship will be nested within, and will receive complementary skills from the host organization, Universite Paul Sabatier (Toulouse, France). Using skills acquired during the previous Marie Curie fellowship and continuing collaboration with the previous host institution (Bournemouth University, UK), completion of the fellowship will facilitate knowledge transfer across the EU and develop the fellow into a world-class, European-based researcher while complementing European priority research areas.

Keywords: biodiversity,ecosystem management,aquatic ecology,anthropogenic impact on ecosystems,invasion,applied ecology,freshwater ecology,modelling and modelling tools (fisheries science)