Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Role of Senescence-associated Cysteine Proteases (SACP)

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-IEF-2008, 2008)
Start date: 2010-03-01
End date: 2010-11-30
Duration (months): 9.0
Total project cost (EUR): 160996.91
EU funding (EUR): 160996.91
Participants: 1
Project status: CLOSED

Despite the importance of senescence in world food production and safety, the proteases responsible for the massive protein degradation during senescence have not been identified. Strong candidates for senescence-associated proteases are members of various cysteine protease families that localize in lytic vacuoles that presumably engulf the chloroplast during senescence. This project aims at identifying the proteases that degrade chloroplasts in the model plant Arabidopsis thaliana. To detect and identify the active proteases during senescence the Activity-based Protease Profiling (ABPP) will be applied. ABPP is a novel functional proteomics technology based on the use of labeled small molecule inhibitors that label proteases in an activity-dependent manner. This technology can be used to show where, when and which proteases are active during senescence, and will reveal proteases that act redundantly. The role of these proteases in senescence will be further studied using reverse genetics and cell biological approaches. This project extends on the expertise and interest of the applicant in senescence and provides an excellent interdisciplinary training in cell biology, molecular cloning and state-of-the-art chemical biology. By performing this work in the Plant Chemetics lab at the Max Planck institute for Plant Breeding Research in Cologne, the applicant will have access to one of the best research and training facilities in Europe and leave at the end of the project with the knowledge and materials to establish an independent scientific career.

Keywords: senescence,arabidopsis thaliana,cysteine proteases,activity-based protease profiling (abpp),natural sciences,plant development
Novel strategies for biomarker discovery and quantification (BIOMAH)

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-IEF-2008, 2008)
Start date: 2009-04-01
End date: 2011-05-31
Duration (months): 26.0
Total project cost (EUR): 181350.76
EU funding (EUR): 181350.76
Participants: 1
Project status: CLOSED

Diagnostics impact our lives in many ways, including disease diagnosis, treatment monitoring and long term environmental biomonitoring. The value of biomarker research in the field of diagnostics and predictive medicine has long been acknowledged. There is an increasing realisation that proteins and peptides mediate a rich information stream reporting on the health of an individual and the emergent techniques of proteomics have made possible the identification, characterisation and quantification of vanishingly low quantities of proteins in complex biological fluids. The analysis of the typical protein pattern from a pathological state by proteomics technology offers the opportunity to discover potentially new biomarkers for premature diagnosis and prognosis. Early developments in proteome analysis were based on protein separation through electrophoresis but it was the development of ‘soft’ ionisation modes and extended mass ranges in mass spectrometry which transformed the subject. Although the hold grail of proteomics (the complete characterisation and quantification of every protein in a cell) has not yet been met, the field has experienced some notable successes, and there has been a remarkable expansion of interest in the ten years passed since the term was first coined, (pubmed: 11 references containing the term ‘proteomics’ in 1996, over 12,000 papers in 2006). One of the areas in which proteomics can contribute a lot is that of biomarkers discovery and quantification. In this project we propose the combination of several novel proteomics approaches namely, positional proteomics, protein equalizer technology and absolute multiplexed quantification (QconCAT), to improve the efficiency of protein and peptide based biomarkers for animal disease diagnosis and monitoring. We will specifically apply these technologies to current challenges in animal health, an area largely left out if compared with human health.

Keywords: animal diagnostics,animal health,biomarkers,proteomics
Mapping Genes involved in Psychiatric Disorders by Admixture Linkage Disequilibrium in Chilean populations (MAPBYADMIXTURECHL)

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: Spain
Call:  (FP7-PEOPLE-IOF-2008, 2008)
Start date: 2009-08-01
End date: 2012-07-31
Duration (months): 36.0
Total project cost (EUR): 272968.4
EU funding (EUR): 272968.4
Participants: 1
Project status: CLOSED

Psychiatric disorders show a complex pattern of inheritance with genetic and environmental factors influencing disease risk. Despite the existence of numerous association studies aiming to identify genetic variants involved in these disorders, inconsistencies in replication studies are common and just a few examples of links between gene variants and psychiatric disorders have been accepted. Several factors may be underlying the failure on replication: difficulties on the definition of clinical phenotypes, existence of distinct disease incidences or disease susceptibility variants among populations and, finally, differences in Linkage Disequilibrium and allele frequencies because of diverse population history. Whole genome association studies (WGAS) are powerful methods to map disease genes, however, these expensive techniques have been unsuccessful for psychiatric disorders. An alternative approach could be the use of mapping by admixture linkage disequilibrium (MALD), an efficient and economical method to localize disease-causing variants between two historically separated populations. MALD has already been successful for identification of disease loci in African American populations and, similarly, it is hoped to be a powerful tool in Latin American populations. We propose the design of an admixture panel of SNPs to map susceptibility genes for psychiatric disorders, particularly substance use and attention-deficit hyperactivity disorders, by the analysis of native (Aymara) and recently admixed populations from Chile. Furthermore, we also plan to assess the repercussions that different genetic structures among populations may have on the interpretation of association studies and, finally, we will search for signals of natural selection and adaptation pinpointing potential genes affecting behavioural traits. This collaborative and interdisciplinary project will also focus on the anthropological and cultural implications of the research and results obtained.

Keywords: complex disease,gene mapping methods,genomics,snp,linkage disequilibrium,evolutionary biology,population genetics,child psychiatry,anthropology,adhd,substance use disorder
Coordinated Control of Patterning and Growth: Mechanisms of Transcriptional Regulation and Dynamics of Dpp Signaling in Flies (GROWTH AND PATTERN)

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: Switzerland
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-03-01
End date: 2011-02-28
Duration (months): 24.0
Total project cost (EUR): 191431.3
EU funding (EUR): 191431.3
Participants: 1
Project status: CLOSED

Animals and their organs become patterned as they grow. One of the most intriguing and challenging questions in developmental biology today is how patterning and growth are coordinated in time and space. Dpp, a member of TGF-β superfamily, with its ability to regulate both processes, serves as a paradigm to answer this question. Our first aim focuses on the logic of transcriptional regulation by Smad proteins, the nuclear effectors of the TGF-β pathways. The Drosophila Smad proteins, Mad and Medea, lead to activation of some target genes while inhibiting others. The putative cofactors required for Dpp-dependent activation have not been identified thus far. Here, I will test the hypothesis that T-box containing proteins, Dorsocross 1, 2, and 3, fulfill this function. In the second part, I aim to monitor Dpp signaling dynamics in vivo. I will fuse Dpp responsive elements to cDNA constructs that encode highly unstable versions of GFP or RFP allowing us to detect small and transient fluctuations in Dpp response. These experiments aim to achieve a detailed spatio-temporal analysis of the dynamics of Dpp signaling in growing tissues. Such in vivo studies will allow putting forward or excluding certain models of how Dpp exerts its multiple functions.

Keywords: developmental biology,cell biology,molecular genetics,animal growth,biochemistry,dpp,signaling dynamics,dorsocross proteins,live imaging,patterning,unstable gfp
Identification and Genetic Profile Characterization of Lgr5 positive Colon Cancer Stem Cells (ICSC LGR5)

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: Netherlands
Call:  (FP7-PEOPLE-IEF-2008, 2008)
Start date: 2009-05-01
End date: 2011-04-30
Duration (months): 24.0
Total project cost (EUR): 161162.47
EU funding (EUR): 161162.47
Participants: 1
Project status: CLOSED

In the murine small intestine, the epithelium renews every five days. This vigorous self- renewing process is controlled by several secreted Wnt factors at the base of the crypt-villus axis. Lgr5/Gpr49 gene is a Wnt target gene that displays a complex expression pattern during embryogenesis, yet expression in most tissues subsides around birth. In adult mice, Lgr5 expression is restricted to rare, scattered cells in multiple tissues including the hair follicles, mammary glands and the intestinal epithelium. In the intestinal epithelium, Lgr5 is expressed throughout the proliferative crypt compartment and has been recently identified as a marker of adult stem cells in small intestine and colon. The cancer stem cell hypothesis postulates that a small reservoir of self-sustaining cells is exclusively able to self-renew and generate the heterogeneous cell population that constitutes the bulk of the tumour. Importantly, Cancer Stem Cells (CSC) not only fuel tumour growth but also tumor metastases. In 2002, Lgr5 was identified as a gene expressed in colon cancer. Therefore, the main goal of this project is to identify colon Cancer Stem Cells by using Lgr5 as a marker and compare the expression profile of this CSC cells with normal adult intestinal Stem Cells. First, I propose to analyse the Lgr5 expression pattern in tumours deriving from the intestinal tract, and compare it with the appropriate non-tumor controls. Following, Lgr5 positive cells will be isolated from fresh tumour suspensions, by antibody-based FACS sorting, and tested for Cancer Stem cell potential. Finally, the expression profile of Lgr5 positive colon Cancer Stem Cells will be compared with the genetic profile of Lgr5 normal intestinal Stem cells, to identify the genes implicated in Stem Cell malignant transformation. The results obtained from these studies would allow identifying potential target cells and target genes for the diagnosis and treatment of colon cancer.

Keywords: cancer stem cells,intestine,health sciences
Developing a 4000-year East African fire history from the Kilimanjaro ice core (PALEOFIRE)

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-IIF-2008, 2008)
Start date: 2009-11-01
End date: 2011-10-31
Duration (months): 24.0
Total project cost (EUR): 173825.86
EU funding (EUR): 173825.86
Participants: 1
Project status: CLOSED

Tropical savanna fires currently comprise approximately two thirds of the global fire budget, making these fires a dominant factor in global carbon emissions, yet little is known how fires have varied through time. This project aims to create a fire history of the East African savanna region over the past 4000 years through the direct determination of levoglucosan in the Kilimanjaro ice core (3º04’S; 37º21’E; 5893 masl, 49 m depth). Levoglucosan is an atmospherically stable molecular tracer of biomass burning which does not degrade when deposited on ice surfaces and is an ideal proxy for quantifying fire activity. The host organization has developed an original method for measuring low concentrations (pg/mL) of levoglucosan in Antarctic ice samples using high-performance liquid chromatography/ electrospray ionization triple quadrupole mass spectrometry. Preliminary analyses on the Kilimanjaro core demonstrated the repeatability and applicability of the technique for tropical glacier ice. A history of fire emissions provides insight into changes in climate, vegetation, and human impacts. Savanna fires tend to be small and numerous which diminishes the likelihood that a single fire event will skew centennial variability and instead the record responds to major climate trends. The impacts of recent pollution emissions will be investigated through measuring anthropogenic atmospheric particular matter including polycyclic aromatic hydrocarbons (PAHs) and heavy metals in the Kilimanjaro ice for the past 200 yrs. Future climate projections suggest increased aridity in the African savanna region which highlights the necessity of understanding past fire activity to place present variability into perspective. The research will increase international cooperation through integrating a novel technique developed in a world-class laboratory with the only existing African ice core to provide a climate record with direct implications for the global carbon cycle.

Keywords: paleoclimate (climate change),aerosols (climate change),carbon cycle (climate change)
North Atlantic Climatic Sedimentary Archives. Provenance and Transport Controls. (NACSA)

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: Spain
Call:  (FP7-PEOPLE-IOF-2008, 2008)
Start date: 2010-02-01
End date: 2011-08-31
Duration (months): 19.0
Total project cost (EUR): 148964.95
EU funding (EUR): 148964.95
Participants: 1
Project status: CLOSED

North Atlantic deep-water formation is the starting step of the Meridional Overturning Circulation (MOC), which redistributes heat from low to high latitudes. Therefore, this region is a key modulator of Earth climate. Changes in this system by external forcings will easily propagate by the MOC, ultimately impacting global climate. Hence, the North Atlantic sedimentary record is an ideal archive of past climate changes. Paleoclimate reconstructions rely critically in accurate determinations of the sedimentary fluxes and the timescales of the mechanisms that trigger and propagate climate changes, yet important timescales such as the transport time of the sediments are still difficult to determine. U-series isotopes disequilibria provide an effective tool for reconstructing these fluxes and constraining these timescales. The time-dependence of 234U depletion relative to 238U in silt sized sediments provides a measure of the comminution age; the time elapsed since their production and final deposition. This can be used as a proxy for climate-induced changes in provenance and deep-current circulation. This proposal aims to reconstruct a high-resolution record of the comminution age, sediment fluxes and focusing, and post-depositional history of the last glacial cycle of ODP site 984 (Bjorn Drift, S Iceland). This interdisciplinary approach will involve U-series isotopes, magnetic properties, composition and sedimentological characteristics of these sediments. This project will test the hypothesis of an alternating source of sediments from Europe to Iceland in phase with glacial and interglacial periods, respectively, rather than a change in bottom currents activity. At the same time, it will provide further grounds for analyzing the response of this proxy in time-scales ranging from abrupt climate forcings to millennial-scale cyclicity during the last glacial cycle, which will help understand the role of the North Atlantic in the Quaternary climatic variability.

Keywords: paleoceanography,paleoclimate (climate change),abrupt climate change,geological oceanography
Requirement for hair cell electrical activity in the auditory sensory map formation: Assessment by genetically controlled inhibition of synaptic activity in mice (SYNACTAUD)

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-IIF-2008, 2008)
Start date: 2010-01-19
End date: 2012-01-18
Duration (months): 24.0
Total project cost (EUR): 228759.18
EU funding (EUR): 228759.18
Participants: 1
Project status: CLOSED

Humans are able to discriminate sounds with frequencies that are separated by no more than 0.1%. This level of performance arises from the exceptional sensory capacities of our cochlea, which detects stimuli through an array of sensory hair cells, spatially organized to follow a gradient of preferred frequency (a tonotopic map). This map is conserved downstream of the cochlea, implying that cochlear neurons must connect hair cells to the cochlear nuclei in the brain with high precision so as to retain the performance of the auditory system. This project addresses the question as to how this precision is achieved. In particular I propose that hair cell activity - both prehearing spontaneous, and stimulus dependent - might play a fundamental role in the fine tuning of this wiring. I will silence hair cell activity and measure the effect of this on their afferent innervation. To do this, I will express exogenous hyperpolarizing channels in the hair cells, using a hair cell specific promoter to prevent any effect on other cell types. Activity dependent plasticity might be temporally delimited in development. I will therefore render our hair cell specific promoter inducible by using a tetracycline responsive element, so as to restrict silencing to a defined time frame. Furthermore, I will make stochastic mosaics using X-chromosome inactivation to randomly silence half the hair cells. I will then test if the silencing of a given hair cell affects the afferent innervation of its neighbors, which would mean that hair cells compete for innervation through their activity. These experiments will provide a new framework to study the wiring of the cochlea, through which new questions may be addressed at the level of the afferent neurons and downstream. The medical implications of this are two-fold: it will help us understand pathologies related to the improper innervation of the cochlea and to develop strategies to improve the wiring of cochlear implants in the brain.

Keywords: neurosciences
Vascular inflammation and atherosclerosis (ATHEROMOTO)

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-IEF-2008, 2008)
Start date: 2009-09-01
End date: 2011-08-31
Duration (months): 24.0
Total project cost (EUR): 239551.42
EU funding (EUR): 239551.42
Participants: 1
Project status: CLOSED

Atherosclerosis is an immunoinflammatory disease of the arterial wall that carries an important socio-economic burden. Atherosclerotic lesions contain activated T cells and specific cytokines along with immunoglobulins. Several studies have shown that atherosclerotic patients develop a perturbed inflammation toward arterial proteins suggesting that autoimmune processes may play a role in atherosclerosis progression. Moreover, patients with aggressive inflammatory diseases such as autoimmune diseases, including SLE, rheumatoid arthritis and type I diabetes, exhibit a higher incidence of atherosclerosis and are at significant risk of premature cardiovascular disease. The continued emergence of cardiovascular diseases and accelerated atherosclerosis in a wide variety of autoantibody-driven diseases emphasizes the need to identify early diagnostic markers and immunotherapeutic targets for the treatment of these complications. The specific hypothesis is that the initiation and progression of atherosclerosis is regulated by autoantibodies directed toward vascular wall components, defects in immune complex (IC) and autoantibody clearance. Our long term goal is to understand the cellular and humoral immunity/autoimmunity basis of atherosclerosis. We will focus our study on analyzing the inhibitory Fc type IIB receptor of immunoglobulin G (FcgRIIB) for the creation of the mouse line of autoimmunity. FcgRIIB is critical in controlling excessive antibody production by B lymphocytes, regulating macrophage reactivity and controlling autoimmunity. We propose to modulate the expression of this “suppressor” of autoimmunity in a hyperlipidemic mouse background. Our specific aims are: Aim I- To create a mouse model that combines of autoimmunity and hypercholesterolemia by silencing the FcgRIIB gene expression in LDLR-/- mouse background. Aim II- To identify panels of antigens that elicit an autoimmune response in this mouse model using a proteomic approach.

Keywords: health sciences,genetically modified organisms,laboratory animal science,proteomics,immunology,cardiology