Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Hepatocyte Growth Factor and Insulin Resistance (HGF-INSR)

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,Spain
Call:  (FP7-PEOPLE-2009-RG, 2009)
Start date: 2010-06-01
End date: 2014-05-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 2
Project status: CLOSED

Insulin resistance is a hallmark of human diseases, including diabetes and obesity, which lead to abnormal glucose and lipid metabolism as a result of impaired metabolic response to insulin. The mechanism underlying the development of insulin resistance remains incompletely understood. Excessive production of pro-inflammatory cytokines by the adipose tissue is linked to insulin resistance. Hepatocyte Growth Factor (HGF) is an adipocytokine elevated in obese subjects, which strongly correlated with the metabolic syndrome. However the role of HGF in the etiology of the insulin resistance remains unknown. Recently, we have demonstrated that HGF is a potent activator of glucose transport and metabolism, and also a strong inhibitor of fatty acid oxidation in rodent myotubes (Perdomo et al., J. Biol. Chem., 2008). In addition, we have generated (i) a conditional transgenic mouse of HGF in the skeletal muscle, and (ii) a conditional knockout mouse of the HGF receptor (c-met) in skeletal muscle. We hypothesized that HGF ameliorates skeletal muscle insulin resistance in vivo. To test this hypothesis, we propose two aims: 1) To investigate the relationship between plasma HGF levels and insulin resistance in humans. 2) To investigate the role of HGF in the insulin-resistant skeletal muscle. Accomplishing this project will elucidate the relationship between plasma HGF levels and insulin resistance in humans and determine its contribution to the etiology and pathophysiology of insulin resistance. A mechanistic understanding of insulin resistance will facilitate the development of therapeutic strategies and identification of new drug targets in the prevention and treatment of diabetes and obesity. Finally, my preliminary data have provided feasibility for the project.

Keywords: diabetology,nutrition related disorders,skeletal system
Functional analysis of the neonatal B cell compartment (NEONATAL B CELLS)

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-2009-RG, 2009)
Start date: 2010-06-01
End date: 2014-05-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Neonatal life is characterized by heightened sensitivity to infectious agents. The sensitivity to infectious diseases is caused by an immaturity of the immunes system which could be due to either qualitative or quantitative differences of neonatal and adult immune cells. In respect to the B cell compartment, several differences have been observed between adults and neonates, including differences in T cell dependent and independent immune responses. To better understand the differences between human neonatal and adult B cells one key question is whether these differences are caused by a different composition of the B cell subpopulations or whether single B cell subsets are intrinsically immature resulting in defective function. B cells have different functions that contribute to regular immune responses. The probably best studied function is the generation of antigen-specific antibodies. In addition to antibody production, B cells can also secrete cytokines and serve as antigen presenting cells. It has been demonstrated in mice that different developmental B cell stages possess very distinct functional characteristics. Much more limited data exist in respect to human B cells. Analysis of human cord blood has demonstrated that it mainly consists out of transitional B cells. Some mature B cells can also be identified based on phenotypical characteristics. But it remains controversial if they are already functionally mature suggesting that there might be also age-dependent functional differences in corresponding B cell subpopulations between neonates and adults. This indicates that it is crucial to understand the functional differences of both adult and neonatal B cell subpopulations when analyzing the mechanisms contributing to the immaturity of the neonatal B cell compartment. Thus, in the current proposal, B cell subpopulations from both neonates and adults will be investigated in respect to early proximal signaling, activation, production of immunoglobulins and cytokines, and the role of BAFF signals.

Keywords: health sciences,immunology,b cells,neonates,infectious diseases
Molecular regulation of blood coagulation factor V: from snakes to humans (MOREFV)

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: Netherlands
Call:  (FP7-PEOPLE-2009-RG, 2009)
Start date: 2010-09-01
End date: 2014-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The overall goal of this proposal is to provide new information on the molecular mechanisms that regulate the cofactor function of blood coagulation factor V (FV). Shedding light on these processes may provide a framework for developing novel strategies for prevention and treatment in cases of disregulation of the blood coagulation response. This is a uniquely complex process that protects organisms from significant blood loss following vascular damage. A failure of this system to respond or to restrict its response can result in life-threatening bleeding disorders or thrombosis. Coagulation FV plays an important role in the clotting system as precursor of FVa, the cofactor for the serine protease FXa that converts prothrombin to thrombin, a key regulatory enzyme in the formation of a blood clot. Interaction of FXa with FVa dramatically enhances its catalytic rate, highlighting the biological significance of FV. Factor Va only interacts with FXa on a phospholipid surface, such as that of platelets or ruptured atherosclerotic plaques. The exact mechanism underlying the membrane-dependence of this interaction is, despite three decades of FV structure-function research, still poorly understood. In the current project, we aim to address this longstanding question using a novel strategy based on a naturally occurring FV variant found in the venom of the Australian snake P.textilis (pt-FV), which has evolved to circumvent the membrane-dependence in FXa binding. We will target several unique structural features of pt-FV that we speculate are involved in its membrane-independent FXa interaction, which will be a) removed from pt-FV and b) introduced into human FV. By characterizing this recombinant FV panel, we anticipate to gain critical insight into the FVa-FXa enzyme complex that is central to coagulation and also into the biology of other macromolecular coagulation complexes, which represents information vital to the engineering of improved therapeutic proteins.

Keywords: thrombosis and hemostasis,coagulation,blood coagulation factor v,protein structure-function analysis,prothrombinase complex assembly
Antigen processing and T cell recognition of intravacuolar parasites (APATRIVAP)

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-2009-RG, 2009)
Start date: 2010-06-28
End date: 2014-06-27
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Antigen recognition by CD8 T cells enables us to combat infectious pathogens, such as viruses and parasites. This feature represents the groundwork for vaccine efficacy. Immune surveillance is achieved by screening short peptides presented by major histocompatibility complex (MHC) class I molecules on the surface of infected cells. Recognition of foreign peptide-MHC I complexes triggers cytokine production and cytotoxicity towards the infected target. CD8 T cells are key for protection against intravacuolar parasites, likes the malaria-causing Plasmodium falciparum and a closely related parasite : Toxoplasma gondii (T. gondii). T. gondii infection can cause life-threatening encephalitis in immunocompromised individuals and severe birth defects if pregnant women get primo-infected. Yet, how the parasite antigens are degraded by the MHC I pathway and how it leads to ultimate establishment of protective CD8 T cells is poorly characterized. Here, using tools and findings obtained during my post-doctoral training in the USA, I propose to use the genetically tractable T. gondii parasites as a model to study T cell immunity to intravacuolar parasites. First, I will address the mechanisms underlying cytosolic access and processing of T. gondii antigens (aim 1). Then we will study the potential strategies used by the parasites to evade CD8 T cell recognition (aim 2). As a longer-term development, we will examine the induction of parasite-specific intestinal T cells in vivo, following oral infection (aim 3). This proposal should have a fundamental significance by revealing novel pathways of antigen processing, as well as a clinical relevance by suggesting ways to manipulate antigen processing and lead to the creation of vaccines against toxoplasmosis. This project will be undertaken in the “Immunology and Infectious diseases” department of the CPTP-INSERM U563 research centre in Toulouse, France.

Keywords: immunology,parasitology,cell biology
Macromolecular Voltage-Gated Na+ Channel Complexes in the Regulation of Normal and Diseased Cardiac Excitability (NAVEX)

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-2009-RG, 2009)
Start date: 2010-07-01
End date: 2013-06-30
Duration (months): 36.0
Total project cost (EUR): 75000.0
EU funding (EUR): 75000.0
Participants: 1
Project status: CLOSED

The dynamic modulation of ion channels is crucial to the regulation of cardiac excitability and defects in channel modulation, associated with congenital and acquired cardiac diseases, lead to the development of life threatening arrhythmias. The dynamic modulation of functional expression of ion channels is achieved through changes in cell surface expression and/or functioning of pore-forming channel subunits. Some of the mechanisms used to achieve these regulations involve interactions of pore-forming channel subunits with accessory subunits and post-translational modifications (PTM) of channel components. The voltage-gated Na+ (Nav) current (INa), generated by Nav1.5 channels, is a key regulator of cardiac excitability, modulating action potential waveforms, refractoriness and propagation. Previous studies have linked family mutations in genes encoding Nav1.5 and Nav1.5 interacting proteins with cardiac arrhythmias, and parallel analyses have suggested roles for these mutations in dysregulating Nav1.5 channel functional expression. However, the mechanisms whereby such native alterations in Nav1.5 function are achieved require identification and functional analysis of in situ Nav1.5 channels. The goal of the present proposal, therefore, is (1) to characterize the native components of Nav1.5 channel complexes, as well as PTM of these components, in the heart, by the use of mass spectrometry analyses; (2) to investigate the role(s) of the previously identified accessory subunit ankyrin G in regulating the functional expression of Nav1.5-encoded INa channels; and (3) to analyze the regulation defects associated with the E1053K mutation in Nav1.5, associated with Brugada syndrome, at the molecular, cellular and whole-animal levels. Altogether, the research proposed will improve our scientific knowledge about ion channel regulation in normal and diseased cardiac excitability, which is needed for improved identification, prevention and treatment of cardiac arrhythmias.

Keywords: health sciences,cardiology,physiology,nav1.5 channels,heart,accessory subunits,proteomics,ankyrin g,regulatory mechanisms,cardiac arrhythmias
Protease Quenched Activity-Based Probes for Targeted Cancer Diagnostic and Therapy (THERAPEUTIC QABP)

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: Israel
Call:  (FP7-PEOPLE-2009-RG, 2009)
Start date: 2010-08-01
End date: 2014-07-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Cysteine proteases play pivotal roles in normal and disease processes. Alteration in cysteine protease expression and activity-pattern are the cause of various human pathologies. Several different cancers types over express members of the cysteine cathepsin proteases family. Previously we have designed and developed “smart” quenched Activity Based Probes (qABPs), that enable real time imaging of cathepsin activity in intact cells. These “smart” probes are fluorescently quenched until binding to an active protease, which causes them to become fluorescent. We have modified these qABPs enabling non-invasive imaging of cathepsin activity in cancer modules in living animals. I propose to generate novel type of ABPs that will target the cathepsin activity in tumors and will have combined imaging and therapeutic capabilities by using photodynamic therapy (PDT) strategies. Theses probes (called Photo Dynamic Activity Based Probes, PD-ABP) will allow concomitant non-invasive cancer detection and targeted treatment. Unlike traditional PDT, these probes would specifically target cancer cells, and the internal quencher would result in overall low light-induced toxicity from unbound probe. Moreover, these probes can be used for real-time tumor imaging prior to light activation, in order to better localize the subsequent photodynamic anti-cancer treatment. In this proposal we will design and synthesize PD-ABPs, we will study their biochemistry in-vitro and in cells and we will use the best PD-ABPs to image and cure cancer in small animals.

Keywords: protease activity,photodynamic therapy,pdt,optical imaging,non-invasive imaging,cathepsins,activity-based probes,cancer treatment,in vivo
Cooperative Multimedia Transmission over Wireless Networks (COOPMEDIA)

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-2009-RG, 2009)
Start date: 2010-04-01
End date: 2014-03-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Future wireless networks will require anytime, anywhere access to high data rate content, such as multimedia, by a growing number of users with an increasing demand for higher quality. Based on heuristics from point-to-point systems, traditional network architectures consist of multiple layers with minimal interaction, each layer taking care of a distinct task such as modulation, routing or error control. While reducing complexity and providing modularity, this layered architecture falls short of exploiting all the available resources and hence, satisfying the growing demand on the user side. This project adopts a cross-layer approach between the application layer requirements and the physical layer constraints and aims at identifying optimal source and channel coding schemes that bring together advanced compression techniques such as multiple descriptions, successive refinement and distributed compression, with promising physical layer techniques for interference management and channel adaptation such as cooperation, superposition and feedback. Aside from theoretical optimality, this project is concerned with developing practically oriented transmission algorithms that can trade-off optimality with modularity and complexity through loose coupling between the source and channel encoders. The goal for the final stage of the project is to complement the theoretical results with analytical and experimental studies for cooperative video transmission over wireless networks. This project will benefit extensively from the tools of information theory, signal processing and optimization theory as well as the hardware infrastructure of the host institution for the implementation part.

Keywords: telecommunications engineering,wireless networks,mimo,video coding,cooperation,feedback,joint source-channel coding
Health Consequences of Water Pollution in China (HCWPC)

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: Israel
Call:  (FP7-PEOPLE-2009-RG, 2009)
Start date: 2010-07-01
End date: 2014-06-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

During the 1980&apos;s and 1990&apos;s, China&apos;s rapid economic growth transformed the country and lifted millions of its citizens out of poverty. The economic boom, however, has been accompanied by environmental side effects, including a severe deterioration in the quality of the country&apos;s rivers and lakes. Concurrent with the decline in water quality in China&apos;s lakes and rivers, the country has witnessed an increase in rural cancer rates. Stomach cancer and liver cancer now represent China&apos;s 4th and 6th leading causes of death, and in combination with other digestive tract cancers (e.g. esophageal) account for 11% of all fatalities and nearly one million deaths annually (World Health Organization 2002). The goal of this project is to assess the causal link between water quality and digestive cancer rates in China. This research question has important implications for public health because of both by the high incidence of digestive cancers, and the fact that those who die from these diseases are relatively young – the average decedent loses 20.2 years of remaining life expectancy. In addition, recent estimates by the World Bank (2006) indicate that as many as half of China’s inhabitants still lack access to safe drinking water. Identifying the causal connection between polluted water and cancer rates is therefore of great importance in China, and in other developing nations where industrialization precedes the widespread introduction of water treatment. Identifying risk factors for cancer is also of general scientific interest an the results and may provide information valuable to public health officials in the European Union and other developed nations.

Keywords: water pollution,china,cancer,industrialization
Effects of wetting and drying cycles on landslide activity (WANDLAND)

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: Switzerland
Call:  (FP7-PEOPLE-2009-RG, 2009)
Start date: 2010-06-01
End date: 2013-05-31
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

The project aims to improve the capabilities to predict the occurrence of landslide crisis episodes. The research activities focus on the changes in the stability conditions of natural slopes when subjected to wet/dry cycling. Soil properties can undergo strong modifications as a consequence of cyclic variations in the degree of saturation, which can lead to a reduction of the available shearing resistance in the long term. The project involves three main research activities. The first phase deals with study of the evolution of natural soil fabrics as a consequence of imposed weathering processes; modern technologies will be applied to analyse those changes at a microscopic level. This analysis is expected to provide a better understanding of the involved physical processes. During the second phase, the effects of cyclic wetting and drying episodes on natural soil samples will be quantified at a macroscale by an extensive laboratory testing programme. The experimental programme involves the use of advanced testing facilities, available at the host institute, which are necessary to control the pore water pressure of the soil in unsaturated states. A new apparatus will also be developed to measure the shearing resistance of the soil after imposing cyclic changes in the degree of saturation using controlled suction. In the third phase, the results from the experimental work will be used to validate a constitutive model for unsaturated soils. This model will take into account the effects of the changes in the degree of saturation on the mechanical response. Finally, the model will be used in a finite element framework to simulate and forecast the behaviours in selected case studies.

Keywords: landslides,weathering,unsaturated soil mechanics,controlled suction testing,constitutive modelling,finite elements simulations,hydro-mechanical coupling
Cerebral representation of object-location memory (SPATIAL MEMORY)

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: Israel
Call:  (FP7-PEOPLE-2009-RG, 2009)
Start date: 2011-01-01
End date: 2016-05-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The uptake and recall of arbitrary associations between objects and their spatial location is a core feature of spatial memory. This form of learning is fundamental to survival across the phylogenetic spectrum. Nevertheless, the hemispheric organization of this function has yet to be understood. Whilst object-location memory is one component of spatial memory most consistently lateralized to the right mesial temporal region, recent research on neurologically healthy participants suggests the existence of task-specificity within the object-location paradigm. Our aim in this project is to investigate the lateral cerebral representation of object-location memory, focussing on two distinct process mechanisms: object processing and spatial-location processing. We propose to study unoperated patients with well-lateralized mesial temporal lobe epilepsy (TLE) with the use of functional Magnetic Resonance Imaging (fMRI) and intracranial EEG recording.

Keywords: neurosciences,neuropsychology,temporal lobe epilepsy,object-location memory,fmri,ieeg