Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Mechanisms of Exertional Dyspnea in Patients with Idiopathic Pulmonary Arterial Hypertension (EDPAH)

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: 2010-11-01
End date: 2012-10-31
Duration (months): 24.0
Total project cost (EUR): 50000.0
EU funding (EUR): 50000.0
Participants: 1
Project status: CLOSED

Activity-related dyspnea appears to be the earliest and dominant symptom limiting exercise in the majority of patients afflicted by pulmonary arterial hypertension. This symptom progresses relentlessly with time leading invariably to avoidance of activity with consequent skeletal muscle deconditioning and poor perceived quality of life. Unfortunately, effective management of this disabling symptom awaits a better understanding of its underlying physiology. A growing body of evidence have highlighted that patients with pulmonary arterial hypertension may present with respiratory muscle weakness and abnormal lung function/respiratory mechanics. Despite these findings, to date little is known about the potential contribution of abnormalities in respiratory mechanics and ventilatory muscle function to dyspnea causation during physical exercise in patients with pulmonary arterial hypertension. This is, therefore, the main focus of the present study, with the aim of identifying potential unexplored physiological mechanisms that can be targeted for therapeutic manipulation.

Keywords: health sciences,medicine,chronic diseases,physiology
Quantum Networks Via Quantum Optical Systems (QUANTNET)

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: Bulgaria
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-10-01
End date: 2013-09-30
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

It is widely appreciated that the most advanced future technologies will exploit the laws of quantum physics. The development of such technologies, in particular the controlled generation, manipulation and characterisation of quantum states and entanglement, poses tremendous challenges, which just a few years ago have been considered nearly impossible to meet. The main objective of this project is to initiate state-of-the-art research in Bulgaria on the development of quantum networks, which are an essential part of future quantum technologies. The work will be conducted in close collaboration with several leading research groups from Oxford, Dijon and Turku. The general aim of the research program is the comprehensive understanding of the potentials and limitations of quantum state manipulation of matter using light and quantum light-matter interfaces. The research plan is focused on the following main directions: (1) optimisation of the efficiency of cavity based photon-generation schemes, (2) optimisation of the efficiency of quantum optical information storage, (3) decoherence and dephasing mechanisms in N-state systems, (4) dephasing upon adiabaticity in simple quantum systems, (5) adiabatic and superadiabatic analytic methods and (6) analytic factorisation methods and applications to coherent quantum control.

Keywords: mathematical physics,atomic physics
Neuronal Alternative Splicing (NAS)

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: 2011-01-01
End date: 2014-12-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Alternative splicing is the process by which multiple mRNA isoforms can be generated from one gene by differential usage of alternative exons in the mature mRNA. It is a major mechanism by which higher vertebrates generate functional complexity of their proteome. Approximately 95% of human genes are alternatively spliced and this process is especially abundant in the nervous system and crucial for proper regulation of neuronal gene expression. Evidence comes from identification of mutations disrupting pre-mRNA sequences, required for alternative splicing, but not for protein coding that cause neurological disease in humans. Moreover, mutations of some RNA binding proteins, with roles in alternative mRNA processing, also result in neuro-developmental disorders and widespread misregulation of alternative splicing. With advancements of high throughput sequencing techniques our knowledge about the kinds of alternative mRNA isoforms and their abundance in different kinds of tissue is rapidly increasing. However, our understanding of the functional consequences of neuron-specific alternative splicing is still very limited. During my postdoctoral studies I have discovered that Hu RNA binding proteins are required for alternative splicing of pre-mRNA targets with important roles in neuronal development and function. I propose to investigate the functions of individual protein isoforms that are translated from Hu-dependent alternative mRNA isoforms. Initially I will focus on studying the functions of the isoforms of the Kif2a gene, which encodes a kinesin motor protein involved in neuronal cytoskeleton dynamics and intracellular cargo transport. I will especially focus on understanding how Kif2a isoforms regulate development of axons and also the transport of cargo to neuronal processes. I believe that my studies will contribute to our knowledge of how neuronal development and physiology is regulated by alternative splicing.

Keywords: neurobiology,gene expression regulation,neuron-specific alternative splicing,hu rna binding proteins,kinesin 2a motor protein
Motivating Parents to Invest in Children (MPIC)

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: 2010-09-01
End date: 2013-08-31
Duration (months): 36.0
Total project cost (EUR): 75000.0
EU funding (EUR): 75000.0
Participants: 1
Project status: CLOSED

It is an empirically established fact that parental investments are crucial in determining adult outcomes. Furthermore, government does not have a direct control over investment children receive at home and as a result cannot force parents to invest. Motivated by these observations, this project pursues a broad program at the intersection of macroeconomics and public economics that will both contribute to the theoretical understanding of how public policy should be conducted in order to encourage parental investment and provide practical recommendations that can be used by policymakers around the world. The first and the main objective of this proposed research is to understand how taxation and social security systems should be jointly designed with income support programs to provide parents with incentives to invest in their children. The second objective of this project is to understand how schooling subsidies should be designed in the presence of parental investments that are (1) hard to monitor and (2) complementary to schooling in determining adult outcomes. The third objective of the proposed research is to answer the questions raised in the first two objectives taking into account that parental investment is crucial in shaping children’s non-cognitive skills as well as cognitive skills.

Keywords: economic policy,public economics,education policy,optimal fiscal policy,macroeconomics
Effects of Progressive Taxation on Economic Growth, Labor Supply and Income Inequality (PROGTAX)

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: 2011-01-01
End date: 2014-09-30
Duration (months): 45.0
Total project cost (EUR): 93750.0
EU funding (EUR): 93750.0
Participants: 1
Project status: CLOSED

The proposed project aims to develop a dynamic macroeconomic model that incorporates progressive taxation and income distribution. For this purpose, it will focus on endogenous growth models with heterogeneous agents and complete asset markets. This model will be used to analyze the aggregate and distributional effects of income tax policy in European economies with respect to major socioeconomic issues such as the declining working hours, income inequality-economic growth relationship, and tax reform proposals. Moreover, the effects of informality will be analyzed for countries with big informal sectors such as Greece, Italy, and Turkey. The proposed project is novel in two main aspects: (1) methodologically, it advances the literature on heterogeneous agent models with complete asset markets and (2) the developed model will be used to analyze important policy issues for Europe that are not discussed at length in a dynamic general equilibrium setting yet.

Keywords: macroeconomics,economic theory,economic growth,labor supply,income inequality,progressive taxation
Statistical Thermodynamics and Computer Simulations of Complex Molecules in Bulk and at Surfaces (STCSCMBS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Research Staff Exchange Scheme
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Poland,Germany
Call:  (FP7-PEOPLE-2010-IRSES, 2010)
Start date: 2011-04-01
End date: 2014-03-31
Duration (months): 36.0
Total project cost (EUR): 132200.0
EU funding (EUR): 132200.0
Participants: 2
Project status: CLOSED

The aim of the project is to perform advanced theoretical and computer simulation studies of nonuniform fluids involving complex molecules. It comprises of three work packages: (i) fluids in contact with tethered layers formed on surfaces and in pores, (ii) substrate driven self-assembly of supramolecular structures formed by complex organic molecules, and (iii) substrate induced self-assembly of nanoparticles with chemical dichotomy. The first work package will involve research of thermodynamic properties and microscopic structures of fluids in contact with a single surface and in pores with walls modified by tethered brushes. We intend to study how these properties depend on the molecular parameters of the model, as well as on thermodynamic variables. We plan to perform studies at different levels of modeling of tethered brushes, from molecular to coarse-grained models, and apply different theoretical tools (density functional theory, molecular dynamics and dissipative particle dynamics simulations). The goal of the second work package will be to study the surface-induced self-assembling of Liquid crystalline dendrimers (LCDr) into bulk as well as surface phases.We will develop a range of surface potentials and study the surface driven self-assembly into monolayer and thin films. Then, we shall investigate the surface induced assembly of liquid crystalline dendrimers into bulk phases in wide slit pores and in the cases of the surface anchoring frustration. The third work package involves studies of behavior of Janus particles in the bulk and at surfaces. In particular, we plan to determine the structure and phase behavior of self-assembled phases of simple dichotomic (Janus) molecules. Then, we shall investigate transport phenomena in self-assembled fluid nanostructures formed by dichotomic molecules and attempt to develop realistic models of self-assembled phases formed by complex organic fluids.

Keywords: surface physics,soft matter and polymer physics,statistical physics,computational physics,chemical physics
DNA-Damage responses: Regulation and mechanisms (DDRREAM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: United Kingdom
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2482492.0
EU funding (EUR): 2482492.0
Participants: 1
Project status: CLOSED

The prime objective for every life form is to deliver its genetic material, intact, to the next generation. Each human cell receives tens-of-thousands of DNA lesions per day. These lesions can block genome replication and transcription, and if not repaired or repaired incorrectly, they lead to mutations or wider genome aberrations that threaten cell viability. To counter such threats, life has evolved the DNA-damage response (DDR), to detect DNA damage, signal its presence and mediate its repair. DDR events impact on many cellular processes and, crucially, prevent diverse human diseases that include cancer, neurodegenerative diseases, immune-deficiencies and premature ageing. While much progress has been made in identifying DDR proteins, much remains to be learned about the molecular and cellular functions that they control. Furthermore, the frequent reporting of new DDR proteins in the literature suggests that many others await identification. The main goals for the proposed research are to: identify important new DDR-proteins and DDR-modulators, particularly those responding to DNA double-strand breaks (DSBs); provide mechanistic insights into how these proteins function; and determine how DDR events are affected by chromatin structure, by molecular chaperones and components of the Ubiquitin and Sumo systems. To achieve these ends, we will use molecular biology, biochemical, cell-biology and molecular genetics approaches, including synthetic-lethal and phenotypic-suppression screening methods in human cells and in the nematode worm. This work will not only be of academic importance, but will also indicate how DDR dysfunction can cause human disease and how such diseases might be better diagnosed and treated.

Keywords: dna damage response,dna repair
COELIAC DISEASE: UNDERSTANDING HOW A FOREIGN PROTEIN DRIVES AUTOANTIBODY FORMATION (AUTO-CD)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: Norway
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2017-04-30
Duration (months): 72.0
Total project cost (EUR): 2291045.0
EU funding (EUR): 2291045.0
Participants: 1
Project status: CLOSED

The goal of this project is to understand the mechanism of how highly disease specific autoantibodies are generated in response to the exposure to a foreign antigen. IgA autoantibodies reactive with the enzyme transglutaminase 2 (TG2) are typical of coeliac disease (CD). These antibodies are only present in subjects who are HLA-DQ2 or -DQ8, and their production is dependent on dietary gluten exposure. This suggests that CD4+ gluten reactive T cells, which are found in CD patients and which recognise gluten peptides deamidated by TG2 in context of DQ2 or DQ8, are implicated in the generation of these autoantibodies. Many small intestinal IgA+ plasma cells express membrane Ig hence allowing isolation of antigen specific cells. Whereas control subjects lack anti-TG2 IgA+ plasma cells, on average 10% of the plasma cells of CD patients are specific for TG2. We have sorted single TG2 reactive IgA+ plasma cells, cloned their VH and VL genes and expressed recombinant mAbs. So far we have expressed 26 TG2 specific mAbs. There is a strong bias for VH5-51 usage, and surprisingly the antibodies are modestly mutated. TG2 acts on specific glutamine residues and can either crosslink these to other proteins (transamidation) or hydrolyse the glutamine to a glutamate (deamidation). None of the 18 mAbs tested affected either transamidation or deamidation leading us to hypothesise that retained crosslinking ability of TG2 when bound to membrane Ig of B cells is an integral part of the anti-TG2 response. Four models of how activation of TG2 specific B cells is facilitated by TG2 crosslinking and the help of gluten reactive CD4 T cells are proposed. These four models will be extensively tested including doing in vivo assays with a newly generated transgenic anti-TG2 immunoglobulin knock-in mouse model.

Keywords: coeliac disease,iga,transglutaminase 2,b cells,t cells,antibodies,pathogenesis,diagnosis
Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons (NANOPHYS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Austria
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-06-01
End date: 2017-02-28
Duration (months): 69.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

In the present proposal, we plan to examine the dendrites, axons, and presynaptic terminals of fast-spiking, parvalbumin-expressing GABAergic interneurons using subcellular patch-clamp methods pioneered by the PI, imaging techniques, and computational approaches. The goal is to obtain a quantitative nanophysiological picture of signaling in this key type of interneuron. By incorporating realistic BC models into dentate gyrus network models, we will be able to test the contribution of this important type of GABAergic interneuron to complex functions of the dentate gyrus, such as pattern separation, temporal deconvolution, and conversion from grid to place codes. The results may lay the basis for the development of new therapeutic strategies for treatment of diseases of the nervous system, targeting interneurons at subcellularly defined locations.

Keywords: gabaergic interneurons,synaptic transmission,dendrites,presynaptic terminals
Neural mechanisms for memory retrieval (ENSEMBLE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: Norway
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-11-01
End date: 2017-10-31
Duration (months): 72.0
Total project cost (EUR): 2499073.84
EU funding (EUR): 2499073.84
Participants: 1
Project status: CLOSED

Memory is one of the most extraordinary phenomena in biology. The mammalian brain stores billions of bits of information but the most remarkable property of memory is perhaps not its capacity but the speed at which the correct information can be retrieved from a pool of thousands or millions of competing alternatives. Despite more than hundred years of systematic study of the phenomenon, scientists are still largely ignorant about the mechanisms that enable mammalian brains to outperform even the best search engines. One of the greatest challenges has been the dynamic nature of memory. Whereas memories can be retrieved over time periods as short as milliseconds, underlying coding principles are normally inferred from activity time-averaged across many minutes. In the present proposal, I shall introduce a new ¿teleportation procedure¿ developed in my lab to monitor the representation of past and present environments in large ensembles of rat hippocampal neurons at ethologically valid time scales. By monitoring the evolution of hippocampal ensemble representations at millisecond resolution during retrieval of a non-local experience, I shall ask (i) what is the minimum temporal unit of a hippocampal representation, (ii) how is one representational unit replaced by the next in a sequence, (iii) what external signals control switches between alternative representations, (iv) how are representations synchronized across anatomical space, and (v) when do adult-like retrieval mechanisms appear during ontogenesis of the nervous system and to what extent can their early absence be linked to infantile amnesia. The proposed research programme is expected to identify some of the key principles for dynamic representation and retrieval of episodic memory in the mammalian hippocampus.

Keywords: memory,hippocampus,neural circuits,place cells,cell assemblies
General light triggered switches and sensors for studying proteins inside the cell (NEXTBINDERS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Switzerland
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2158800.0
EU funding (EUR): 2158800.0
Participants: 1
Project status: CLOSED

The overall objective is to develop general strategies for creating sensors and switches that work inside cells. They will be engineered from Designed Ankyrin Repeat Proteins (DARPins) as general binding proteins that function inside cells and can be generated against any target by selection and directed evolution. Light-triggered switches will be engineered by placing a LOV domain from phototropin in such a way across the DARPin that it is blocked, and only the light-triggered conformational change makes the DARPin accessible. As a second strategy, DARPins specifically recognizing each one of the two isomers of azobenzene, which can be interconverted by light, will be used within light-dependent cross-linkers. Third, DARPins selected to tightly bind fluorogens, by which these small molecules increase their fluorescence by several orders of magnitude, will be converted into general sensors of the conformation of a target protein working within the cell: large DARPins will be created with overlapping binding sites for the protein of interest and the fluorogen. By using DARPins which can selectively distinguish conformations of the target protein, the conformational changes are made visible in a spatiotemporal manner in an individual cell. As proof of principle, we will generate sensors and switches for the kinase domains of the four ErbB receptors, pivotal in signal transduction in human cancers. To increase the impact of this research further, these novel switches and sensors have to be efficiently brought into cells. For this purpose, adenovirus will be engineered for novel cell tropism, also by using DARPins, to homogenously infect tumor cells to study ErbB signaling and the effect of therapeutics in real time in a receptor-differentiating manner. While tested for the ErbB family as a prototype, the strategies to be developed will be totally general and should open up novel ways of studying signaling within cells in real time and with high spatial resolution.

Keywords: protein engineering