Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Structural characterization of filamentous bacteriophage viruses by magic-angle spinning solid-state NMR spectroscopy (PHAGE MAS SSNMR)

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-2007-4-3-IRG, 2007)
Start date: 2008-03-01
End date: 2012-02-29
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Filamentous bacteriophages comprise a family of viruses that share a similar virion structure and life cycle. The virion is composed of a circular ssDNA wrapped by thousands of similar copies of a major coat protein and several different minor coat proteins in both ends. Due to the mass (tens of MegaDaltons) and dimensions (~7 nm in diameter, 600 – 2000 nm in length) of filamentous phages, structural models have been obtained primarily from fiber diffraction, and from static solid state NMR of aligned concentrated solutions. Yet, these models are incomplete, and vary even within individual virions. Also, some key questions regarding DNA structure, subunit-DNA interactions, microscopic polymorphism, and more, remain unclear or are in debate. Magic-angle spinning solid state NMR (MAS SSNMR) has been shown recently to be a complementary and successful method for studying the structure and dynamics of biological macromolecules. Examples are membrane proteins, protein aggregates and fibrils, and recently, the Pf1 filamentous phage. Also, sample preparation for MAS SSNMR is more flexible, and measurements can be performed in conditions, which are either biologically relevant, or important for their biophysical characterization. The goal of the proposed project is to structurally characterize and compare the three key phages fd, Ike, and Pf3, using MAS SSNMR as a principal spectroscopic tool. These phages were chosen, since they represent different structural properties of such virions. We anticipate that our proposed studies will resolve some of the key questions regarding the structural assembly of filamentous phages, and enhance our understanding on the possible ways in which these phages assemble at their host bacteria. Our results will also provide suitable model systems for studies of other complex biological systems.

Keywords: structural biology,magic angle spinning,solid state nmr,filamentous bacteriophage,protein-dna interactions
The endocrine control of histone acetylation in regulating gonadotropin gene expression (HATS)

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-2007-4-3-IRG, 2007)
Start date: 2009-02-01
End date: 2013-01-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The gonadotropin hormones regulate reproduction, showing dynamic fluctuations in their expression levels across the life cycle to determine reproductive potential. The principle determinant of their expression is the hypothalamic hormone, GnRH, which stimulates both their synthesis and secretion. Aberrant GnRH exposure can stimulate precocious puberty, and we have shown previously that GnRH is able to overcome prolonged periods of gonadotropin gene repression, through removing histone deacetylases (HDACs) from their promoters. While HDACs repress transcription through nucleosome compaction, active histone acetylation on the protruding N-terminal tails of histones H3 and H4, both loosens the packaging of DNA and can serve as a signal for the binding of additional transcription factors. Research on the gonadotropins has revealed a number of transcription factors that activate both basal and GnRH-stimulated gene expression, but the role of the histone modifications has not been studied. The first aim of this study is to investigate which histone acetyl transferases (HATs) activate the gonadotropin gene promoters in response to GnRH treatment, whether they have any target specificity on the H3 and H4 tails, and how they are recruited. Histone acetylation is just one of the various covalent modifications which are required for activating transcription, although the regulation and interdependency of many of these modifications are not yet clear. We will therefore also study the requirement and consequence of the histone acetylation for other histone modifications such as phosphorylation and methylation at these gene loci. This is a novel aspect of GnRH signaling to the gonadotropin genes, that both provides a suitable model for understanding basic mechanisms of hormone-induced chromatin modifications, and also has implications for clinical relevance in the field of reproductive endocrinology.

Keywords: endocrinology,reproduction,molecular biology,transcription,chromatin,developmental biology,histone modifications
Microtubule organizing centers and microtubule nucleation in mitosis. (MTOC FUNCTION)

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-2007-4-3-IRG, 2007)
Start date: 2008-07-21
End date: 2012-07-20
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Centrosomes are multifunctional organelles crucial for a large number of cellular functions including the organization of microtubules. In mitosis centrosomes contribute to assembly, orientation and function of the mitotic spindle, which is important for proper segregation of the chromosomes. Defects in centrosome number and function are strongly associated with the cancer phenotype and centrosomes offer potential new targets for anti-mitotic cancer drugs. Recent data suggests that microtubule organization at centrosomes also has implications for aspects of cellular differentiation, and that several human genetic diseases can be linked to centrosome malfunction. The characterization of proteins required for the function of the centrosome as a microtubule organizing center (MTOC) might reveal how structural and functional centrosome aberrations affect genomic stability and cancer development as well as developmental processes. I will study a key component of the centrosome and other MTOCs, the gamma-tubulin complex, and identify and characterize additional centrosome proteins involved in microtubule organization. I propose to: 1) analyze the mitosis-specific function and regulation of gamma-tubulin and associated proteins, 2) reconstitute the centrosomal attachment and function of the gamma-tubulin complex in a purified system in vitro, and 3) test proteins of the centrosome proteome for localization to a non-centrosomal microtubule organizing center, to identify and characterize those centrosome proteins specifically involved in microtubule organization.

Keywords: centrosome gamma-tubulin microtubule cytoskeleton spindle mitosis cancer
An Investigation into Tolerance Induction by Extracorporeal Phototherapy (ECP TOLERANCE)

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: Germany
Call:  (FP7-PEOPLE-2007-2-2-ERG, 2007)
Start date: 2008-07-01
End date: 2011-06-30
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

Allogeneic haematopoietic stem cell transplantation (HSCT) is an important curative therapy for a large number of hematological diseases. Graft versus host disease (GVHD) remains the major complication of allogeneic HSCT, which occurs in 40-60% of transplant recipients and could be directly responsible for 25% of transplant related mortality and a significant proportion of transplant related morbidity. Established immunosuppressive treatments are of limited efficacy and have significant side effects. Extracorporeal Phototherapy (ECP) is an effective treatment for GvHD. Importantly, infection and relapse rates are not increased in the course of ECP treatment. Hence, ECP is an exciting model to study tolerance mechanisms. ECP actions include apoptosis, cytokine modulation and the induction of regulatory T cells but the underlying mechanisms have not been revealed yet. Antigen presenting cells like dendritic cells (DCs) are thought to be important in mediating ECP effects. The project aims at comprehensively analysing ECP effects with special focus on the modulation of dendritic cells by ECP induced apoptotic cells. A unique modified skin explant model simulating ECP treatment for GvHD will be used to analyse immunoregulatory characteristics of DCs and T cells modified by apoptotic cells. Proteins known to carry regulatory potential will be assessed and mRNA expression arrays will be used to identify novel molecules involved in tolerance. The project will furthermore explore if ECP induced apoptotic cells have unique properties by comparing different methods of apoptosis induction. The skin explant model will be used in an antigen-specific context to clarify whether ECP actions are T cell clone specific. The last part of the project will analyse DNA polymorphisms of molecules identified during the course of the project to predict reponses to ECP in patients. In summary, ECP will be used as a model to study tolerance and derive novel tolerogenic strategies.

Keywords: medical sciences,immunology,transplantation,graft-versus host,photopheresis,tolerance
Molecular Analysis of Synapse Formation, Maintenance and Disassembly at the Drosophila neuromuscular junction (SYNAPSE STABILITY)

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: Switzerland
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2008-06-01
End date: 2012-05-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The refinement of neuronal circuits requires both a stabilization of existing synaptic connections and a disassembly of previously functional synapses. While the mechanisms of synapse formation have been extensively studied, very little is known about the molecular mechanisms that are responsible for the stabilization of synaptic connections. Any inappropriate loss of synaptic stability will lead to disruptions of neuronal circuits and finally to neurodegenerative disease. Therefore, the identification of the molecular mechanisms that regulate synapse stability versus disassembly may help to understand how synaptic circuits are modified in response to signaling events and may provide useful insights towards our understanding of neurodegenerative disease. I am combining the advantages of Drosophila genetics, cell biology and physiology with a high-resolution assay for synapse retraction to identify and characterize genes involved in synapse formation, stability and disassembly. My postdoctoral work has highlighted the importance of a presynaptic cytoskeletal network that links cell adhesion molecules to the underlying actin and microtubule cytoskeleton to achieve normal synapse formation and stability. Here I propose to define the signaling systems that control the assembly and stability of the presynaptic network during synapse formation and maintenance. In the first aim I will focus on the adaptor molecule Ankyrin2 that has the potential to directly link synaptic cell adhesion molecules to the presynaptic microtubule cytoskeleton. The second aim addresses how actin dynamics contribute to normal synapse formation and stability. Finally, I will use forward genetic approaches to identify novel molecules required for synaptic stability. Together these projects will provide insights into the molecular mechanisms that regulate synapse stability in response to intrinsic and extrinsic signaling systems within neuronal circuits.

Keywords: neurobiology,cell biology,genetics,drosophila melanogaster,synapse biology,neurodegenerative disease,actin,microtubules
Bidirectional interactions between cardiomyocytes and cardiac stem cells in the adaptive response to physiological stress (CSC PHYSTRESS)

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: United Kingdom
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2008-03-01
End date: 2012-02-29
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Stem cell therapy for the treatment of many degenerative and life-threatening diseases has opened up a promising and exciting outlook for the future of medicine and drug therapy. The recent discovery of cardiac stem cells (CSCs) present in the adult mammalian heart, including the human, has stimulated a new and exciting field for cardiac biology. These resident cells express defined stem cell markers (i.e. c-kit), are clonogenic, self-renewing and multipotent. They also have significant regenerative potential when injected into the infarcted rat myocardium. However, despite rapid progress, many questions remain to be answered before the clinical potential of adult cardiac stem cells can be fully realized and exploited. Indeed, identifying factors that regulate cardiac stem cell fate is of great importance to design better protocols and interventions for the regeneration of functional contractile mass following myocardial injury. Recent research by myself and colleagues has identified CSC activation and new myocyte formation as playing a key role in exercise training-induced cardiac physiological remodelling in the mouse. In this project, using a controlled-intensity exercise training model and novel genetic fate mapping of CSCs, I will answer the much debated question of whether CSCs are the direct source of new myocyte formation in the adult mammalian mouse heart. Following this, through gene expression array I will determine whether myocyte-dependent growth factor release drives the exercise training induced cellular adaptation of the heart. Then I will evaluate in vitro the role of these pivotal growth factors in regulating CSC fate. Obtaining this key information on stem cell biology will be useful for manipulating the regenerative potential of these cells and therefore in designing the most optimal cellular therapy protocol for myocardial regeneration/repair.

Keywords: cell biology,physiology,stem cells,growth factors,exercise training,cardiomyocytes,myocardium,myocardial regeneration,multi-potency,heart disease,stem cell therapy
Democratic Peace Theory: Recent Developments (DPTRD)

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: Italy
Call:  (FP7-PEOPLE-2007-2-2-ERG, 2007)
Start date: 2008-03-15
End date: 2011-03-14
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

In the last two decades political philosophers and international relations (henceforth IR) scholars have widely debated the so called “democratic peace” thesis, i.e. the idea that liberal democracies are more pacific than authoritarian regimes. The history of the last two centuries suggests that democracies have never fought wars against each other (although they have often waged wars against authoritarian states). The democratic states – this is the core of the thesis – have constituted a kind of “separate peace”. The root of this thesis is to be found in the Kantian essay To Perpetual Peace (1795). Kant believed that peace is secure only if the citizens’ interest in avoiding the atrocities of war will influence the foreign policy of their government. And this clearly happens only if the government represents the people’s will. With a series of famous articles published from 1983 to 1986 Michael Doyle has placed Kant’s intuition back to the center of the international debate. The jointly Kantian-Doyleian thesis has been subject to a series of criticisms, arising mainly, but not only from the realist school. The proposed project intends to assess critically the debate, to select the most promising variations to the original Kantian-Doyleian Thesis, and to test the validity of the whole approach against the experience of the war in Iraq.

Keywords: humanities,social sciences
Quantum algorithms and the foundations of quantum computation (QAQC)

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: Latvia
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2008-05-01
End date: 2012-04-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Quantum computing (and, more broadly, quantum information science) is a new area at the frontier of both computer science and physics. The laws of quantum mechanics are profoundly different from conventional physics. Quantum computing studies how to use them for the purposes of computer science and information processing. Quantum computing (and, more broadly, quantum infromation science) has seen tremendous progress in the last 15 years, both on its theoretical side (with Shor's quantum algorithm for factoring and Grover's quantum search algorithm) and experimental side (with small scale prototypes for quantum computers and commercially available systems for quantum cryptography). We plan to address the following questions: - What problems can we solve on a quantum computer (besides factoring and search)? More generally, can we isolate general principles for designing quantum algorithms? - What are the problems that {\em cannot} be solved by a quantum computer? Which of the conventionally hard problems remain hard, even if quantum computers are available? - What are the fundamental properties of quantum states and what insights do they provide for quantum computing? In particular, we plan to study randomness and pseudorandomness in the quantum world.

Keywords: technological sciences,quantum computing,quantum information,quantum states,theory of computation
Characterisation of the role of LHC-related proteins in photosynthesis (LHC-REL)

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: Sweden
Call:  (FP7-PEOPLE-2007-2-2-ERG, 2007)
Start date: 2008-03-01
End date: 2010-02-28
Duration (months): 24.0
Total project cost (EUR): 30000.0
EU funding (EUR): 30000.0
Participants: 1
Project status: CLOSED

Life on Earth depends on photosynthesis, the conversion of light energy into chemical energy. Light is collected by pigment binding multisubunit proteins, called light harvesting antenna complexes (LHC). The light harvesting proteins of higher plants belong to a large family; these polypeptides comprise up to 75% of the chloroplast grana membrane proteins. Their expression is regulated by the quality and quantity of light. There are a number of proteins in the photosynthetic membranes which show sequence similarity to the light harvesting proteins. These LHC-related proteins are encoded by the so-called Lil (light harvesting like) genes. They include early light induced proteins (ELIPs), one-helix proteins (OHP) and stress-enhanced proteins (SEP). These are short-lived polypeptides which accumulate in the thylakoid membrane during light stress. Unlike LHC complexes their primary function is not light harvesting but rather protection against light stress. There are mutant Arabidopsis lines available lacking these LHC-related proteins. The aim of the project is the detailed characterisation of these mutants including studies of their photosynthetic performances, biochemical and metabolomic characterisations and fitness studies in field conditions. The project will also focus on the investigation of the location and interacting partners of the Lil proteins, which knowledge is necessary for the understanding of their mode of action. The targets of this project will allow a better understanding of the fine-tuned balance of light harvesting and photoprotection, and the responses of plants to light stress, which knowledge will be beneficial to agriculture as well by helping the improvement of crop plants to withstand stress conditions, such as high light exposure.

Keywords: photosynthesis,light harvesting,photoprotection,plant fitness,stress,antenna,lhc,light harvesting like proteins,lil,elip,sep,ohp
Sarcomeric-Simulation AppRoach in a COmputational Multiscale EnviRonmEnt (S-SARCOMERE)

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: United Kingdom
Call:  (FP7-PEOPLE-2007-2-2-ERG, 2007)
Start date: 2009-01-01
End date: 2011-12-31
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

First, a simulation environment of the sarcomere will be developed by using lumped parameter models. This model will be incorporated into existing models of the cardiac contraction to eventually build a multi-scale model of the cardiovascular loop. At a later stage, this model will be coupled to local 3D models of cardiac devices. The study will focus on one specific application in cardiovascular engineering: valve closure force. Whilst forces of closure of prosthetic heart valves are an important characteristic with respect to the design, they are very difficult to quantify. Also, cavitation might be a problem, as could lead to catastrophic failure or blood damage. Closure lasts for only about 35 ms, and there are no adequate models that can predict or quantify the effect of local/cellular events of chemical, biochemical or mechano-electrical nature at the ventricular level on the closure forces. For potentially high-risk patients is possible that pharmacokinetical intervention may reduce the cavitation potential of the valve and risk of fracture. We propose to develop the first coherent multi-scale model of the system taking into account the cellular mechanisms of cardiac contraction, with feedback between electrochemical events in the vessel wall and detail haemodynamic characteristics of the flow

Keywords: biomedical engineering,simulation engineering,biophysics,medical physics,computational biology