Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
THE ROLE OF THE MTOR SIGNALING PATHWAY IN NEUROGENESIS AND ITS IMPLICATIONS FOR THE REGULATION OF ENERGY BALANCE (TOR AND NEUROGENESIS)

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-2007-4-3-IRG, 2007)
Start date: 2008-03-01
End date: 2010-02-28
Duration (months): 24.0
Total project cost (EUR): 50000.0
EU funding (EUR): 50000.0
Participants: 1
Project status: CLOSED

The major interest of my research activity is to understand the pathophysiological mechanisms leading to the development of obesity, particularly focusing on the role of the central nervous system (CNS) in this context. The CNS is the critical organ for the coordination of intracellular metabolic processes that are essential to guarantee energy homeostasis at the organism level. Thus, centering my studies on the atypical kinase mammalian Target Of Rapamycin (mTOR), I recently demonstrated that this evolutionarily conserved fuel sensing pathway integrates sensory inputs from nutrients and hormones within the hypothalamus, in order to modulate food intake and body weight. The ciliary neurotrophic factor (CNTF) is a cytokine whose central administration reduces body weight even in leptin-resistant states, including diet-induced obesity, and causes a weight loss that is maintained after therapy discontinuation. The explanation for this long-term effect of CNTF on energy balance likely resides in its newly described ability to induce neurogenesis within the adult murine hypothalamus. Cellular development and differentiation are tightly coordinated with nutritional status; and induction of mitogenic signaling and neuronal differentiation is known to involve modulation of the mTOR signaling. Thus, I propose that the CNTF effects on neurogenesis and energy balance require the activation of the hypothalamic mTOR signaling pathway. To investigate this hypothesis, I will use a multidisciplinary approach, including the use of genetically modified mice, specific behavioral paradigms and molecular strategies. These studies will clarify the role of cellular fuel sensing mechanisms in the regulation of energy balance and possibly highlight the function of processes, such as neurogenesis and neuronal differentiation, which might be important for the appropriate regulation of energy balance within the hypothalamus and that might require a functional mTOR signaling cascade.

Keywords: brain research,physiology,neurobiology,feeding behavior,neurogenesis,target of rapamycin,energy balance
Spatial Competition between Railway Stations (SCARSE)

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: 2008-03-01
End date: 2011-02-28
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

Policy makers and railway operators share a similar goal, increasing the use of rail, whether to meet policy goals (e.g. improved accessibility) or to improve the railways' financial viability. The key factor in rail use is the number and location of railway stations and their catchment area. Opening new stations, to reduce access/egress distance to/from the station, can be a way to increase rail use, but it is costly and can result in travel time penalties for passengers using the line but not the (new) station. Due to the value of transport services they provide (node value) and the value of other services (e.g. retail - place value), railway stations have an economic impact on their surroundings. This is (partly) manifested in the prices of real-estates around stations. This impact can play an important role in the financial viability of the railways, and in itself can justify changes in the number and location of railway stations in a given network. Spatial competition between stations would normally exist in large cities where demand for rail is served through several railway stations. Such competition can be counter productive in terms of increasing rail use and improving the railways' financial viability. In the above context the research main question is: Do overlaps in railway stations’ catchment and impact areas represent a burden on railways' financial viability while not contributing to the use of rail as a mode of transport? To answer the above question, the following objectives are set, which also illustrate the methodology adopted. • Measuring railway stations’ catchment areas and assessing the factors influencing it • Measuring railway stations’ impact areas and assessing the factors influencing it • Mapping the railway stations’ catchment and impact areas and identifying overlaps • Evaluating the extent to which overlaps in the catchment and impact areas of railway stations affect overall rail use and the railways’ financial viability

Keywords: economics,urban transport,rail transport,railway station,catchment area,land value uplift,rail policy,spatial analysis,rail financial operation
Characterizing the oncogenic properties and target genes of the splicing factor protooncogene SF2ASF (ONCOGENIC SPLICING)

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

Cancer is a multifaceted disease involving numerous mutations in many tumor suppressors and oncogenes. Elucidation of the molecular basis of cancer has been and continues to be a major goal of biomedical research in the past few decades. Previous evidence suggests a connection between alternative splicing and cancer, and the activities of many oncogenes and tumor suppressors are modulated by alternative splicing. We found recently that the splicing factor SF2/ASF is a potent proto-oncogene, capable of transforming immortal and primary fibroblasts when slightly overexpressed. We found that SF2/ASF is upregulated in a set of human tumors and SFRS1, the gene coding for SF2/ASF is specifically amplified in some breast tumors but not in normal breast tissue from the same patient. Moreover, we identified several endogenous splicing targets of SF2/ASF, among them a novel oncogenic isoform of the mTOR substrate, S6K1, which is essential for SF2/ASF-mediated transformation. Based on these findings, we propose to study the detailed mechanisms of SF2/ASF-mediated transformation in cancer. We will dissect the specific functions of SF2/ASF required for its activity as an oncoprotein, through a structure-function analysis of its specific domains, using deletion mutants that are impaired in specific biological processes. We hypothesize that the splicing activity of SF2/ASF is essential for its transforming activity. Thus, we wish to identify and validate the regulated alternative splicing targets of SF2/ASF. We will identify these splicing targets on a genome-wide scale, using an exon array recently developed by Affymetrix. These experiments will shed light on the molecular mechanisms by which SF2/ASF is upregulated in human cancer and can lead to transformation. The analysis of a novel type of proto-oncogene has the potential to uncover new molecular aspects of cancer, and to provide new opportunities for diagnosis and therapy.

Keywords: health sciences,alternative splicing,oncogenes,exon array,transformation
Strategic Management of Emergent Nanotechnologies (SMENATECH)

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: 2008-04-01
End date: 2011-03-31
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

The proposed research programme sets out to investigate the multi-faceted nature of the management and development of emerging nanotechnologies through the integration of a variety of conceptual perspectives as well as different levels of analysis. It responds to the declared need for there to be a better understanding of the changing role of knowledge and technology in the creation of a competitive Europe. Advances in nanoscience and nanotechnology create such system of emerging technology innovation where the agents strive to reconcile the potential benefits of radical technological, economic and social change together with their associated uncertainty, ambiguity and instability. Emergence of nanotechnology represents a significant opportunity for researchers to investigate how different agents develop dynamic capabilities and create new business models. This proposal will enable the study of how individual agents engage with the strategic and wider social and economic context in order to explore opportunities offered by nanotechnology. It also offers an ideal setting to study the collaborative nature of emergent technology innovation more generally. Although this project is rooted in the social sciences it requires for serious attention to be paid to the practice of science and technology. This research programme represents the nucleus of a wider research agenda that is taking place at the host institution. This research on the business and managerial aspects of nanotechnology innovation will complement world class research in the area of nanotechnology. By so doing it will create knowledge relevant to scientists, engineers, entrepreneurs, managers and research policy makers. The project also supports the ambition of the applicant to continue an international career within the European research area and as such embody the ideals of the Marie Curie programme.

Keywords: management of enterprises,technology,innovation,strategic management,nanotechnology
Role of E3 Ub-ligases in TGF-beta signaling and tumorigenesis (E3ANDTGFBINCANCER)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: European Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2007-2-2-ERG, 2007)
Start date: 2008-04-01
End date: 2011-03-31
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

The binding of TGF-b to its receptors induces phosphorylation of Smad2 and Smad3, their subsequent association to Smad4 and their nuclear translocation. In the nucleus, the Smad3/Smad4 and Smad2/Smad4 heterodimers act as transcription factors and induce specific target genes. TGF-b pathway has a tumor suppressor function characterized by its ability to inhibit cell growth. Many cancer cell lines have acquired resistance to the antiproliferative effect of TGF-b. This is mainly achieved through loss of function mutations or deletions that affect TGF-b receptors or Smad4, particularly in colon cancer and pancreatic cancer. During my Postdoctoral training in Caroline Hill’s laboratory, I have shown that the E3 Ub-ligase Arkadia is involved in the degradation of the transcriptional repressor SnoN and is therefore absolutely required for the activation of Smad3/Smad4 target genes such as PAI-1. The laboratory of Azeddine Atfi has recently performed a two-hybrid screen using another repressor of the pathway, TGIF, as a bait. This study has led to the identification of a new partner of TGIF, TIP11 (TGIF interacting protein 11), which is a new potential E3 Ub-ligase. Preliminary results indicate that TIP11 also contributes to TGF-b responses. Recently, we both have independently identified that Arkadia and TIP11 can be altered in tumor cell lines. Our study aimed to determine whether these two E3 Ub-ligases, essential for the TGF-b pathway, are novel tumor suppressor genes. Our objectives are: (1) to identify Alterations of Arkadia and TIP11 in human carcinoma cell lines and tumor samples. (2) to study the function of Arkadia and TIP11 by reintroducing Arkadia or TIP11 in deficient cell lines, in order to better understand their role in TGF-b signaling and tumorigenesis. (3) to unravel the mechanism of action of these two E3 Ub-ligases by a biochemistry approach. (4) to identify novel binding partners of Arkadia and TIP11 by performing a two-hybrid screen.

Keywords: cell biology,genomics,human biology,molecular biology,oncology
Molecular studies of the ruminal microorganisms involved in methane production: towards more environmentally friendly European livestock (METANORUMEN)

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: Spain
Call:  (FP7-PEOPLE-2007-2-2-ERG, 2007)
Start date: 2008-05-01
End date: 2011-04-30
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

This proposal aims to apply genomic technologies to improve our understanding of the microbial rumen population involved in methane production and the factors determining the variability between individuals. The professional objective is to reintegrate myself in an existing leading group in Animal Nutrition and establish myself as a researcher in my home country (Spain) in order to lead my own research activity. The research objective of this proposal is to apply genomic technologies to improve our understanding of the population involved in methane production in the rumen and the factors that determine differences between individuals. The knowledge obtained will be applied in animal production systems to reduce methane emissions and therefore increase animal productivity and greenhouse effect. The factors affecting methane production are numerous: microbial population in the rumen, type of diet, feeding pattern, compounds with antimicrobial effects and type of animal. Therefore, a multidisciplinary approach is required: anaerobic and molecular microbiology, animal physiology, plant physiology and bioinformatics should be integrated in the project.

Keywords: health sciences,methane emissions,rumen,archaea,livestock,molecular tools
Multi-Chromophore Systems for Light Induced Processes and Light Triggered Devices (ERG-LIGHT)

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: 2008-03-01
End date: 2011-02-28
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

The general aim of this project is to gain new knowledge and a deeper understanding of novel two- and three-dimensional nanometer-sized assemblies of chromophores in terms of construction, characterization, photoinduced or electro-optical properties, molecular recognition and selective catalysis, antiviral and anticancer properties. The specific aim of this project is the construction, via a supramolecular approach, of novel photoactive multi-chromophore assemblies. The supramolecular synthetic strategy, by virtue of its modular and highly flexible nature, will allow to perform the selective variation of the components and investigate their influence on the properties of the final assemblies, while keeping at a minimum the synthetic effort. The ultimate aim of this project is the preparation of new photoactive nanosystems to be used in technological applications. The project will be developed within an extended frame of scientific national and international collaborative networks.

Keywords: technological sciences,natural sciences,health sciences,light-induced processes,surfaces,nanoparticles,recognition,catalysis,photodynamic terapy,nano materials
DNA Replication and Biomolecular Recognition (QUANTUMBIOLOGY)

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: Spain
Call:  (FP7-PEOPLE-2007-2-2-ERG, 2007)
Start date: 2009-03-01
End date: 2012-02-29
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

DNA replication is at the core of life and strongly appeals to the imagination. It is also a textbook example of template directed synthesis, involving enzyme-assisted molecular recognition of incoming bases by the template strand. Yet, in spite of much effort, many fundamental questions about its mechanism are open. In this research line, using a quantumchemical approach, we aim at two main objectives: (1) understanding the electronic nature of molecular recognition in DNA base pairs, in artificial mimics thereof and in larger, macromolecular aggregates of related systems; (2) unravelling the mechanism of the highly accurate, enzyme-assisted DNA replication and, in particular, understanding the role of hydrogen bonding, steric factors and solvent effects in this multistep process. The two subprojects are intimately connected and reinforce each other. We wish to explore the possibilities of rationally designing monomers whose capability to undergo self-organization can be switched on or off chemically (by a third agent) or physically (by radiation). Potential applications are the controlled and selective formation of macromolecules, nanostructures and materials. Furthermore, a better knowledge and so tuning and control of the DNA replication process is envisaged. On the long term, we hope to contribute to the development in general of quantumchemical approaches to biologically relevant problems, i.e., quantumbiology. Our computations are mostly based on density functional theory (DFT) but also on high-level ab initio theory as well as molecular mechanics (MM). Extensive validation studies, by others and us, have shown that DFT is the method of choice, both in terms of efficiency and accuracy, for large biochemically relevant molecules that involve hydrogen bonding. Our approach furthermore involves the application and further development of hybrid QM/MM techniques for tackling realistic model systems of the template–primer–enzyme complex involved in replication.

Keywords: computational chemistry,molecular chemistry,reaction mechanisms ands dynamics,structural chemistry
Effects of atorvastatin on vascular and myocardial redox state and inflammatory mechanisms in patients with ischemic heart disease (STATINS-REDOX)

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: Greece
Call:  (FP7-PEOPLE-2007-2-2-ERG, 2007)
Start date: 2008-04-01
End date: 2011-03-31
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

Ischemic heart disease (IHD) is characterised by increased systemic oxidative stress status. Free radicals activate redox sensitive pathways responsible for the production of inflammatory mediators with key role in IHD. Statins have a beneficial role in coronary atherosclerosis, but their potential effect on key features in the pathophysiology of IHD is unclear. In this context, statins may have a beneficial effect in IHD by modifying myocardial and vascular redox signalling. In part A of the study, we will obtain segments of internal mammary arteries (IMA) and saphenous veins (SV) from 60 patients with ischemic heart disease (IHD) undergoing coronary bypass operation. In these vessels we will evaluate the direct effect of atorvastatin on the main sources of superoxide (O2-) radicals generation (uncoupled nitric oxide synthase (NOS) and NADPH-oxidase), by using an ex-vivo setup. We will also investigate the direct effect of atorvastatin on the expression of adipokines (cytokines with important paracrine/endocrine role in IHD) in different types of adipose tissue. We will also examine the individual effect of each adipokine on vascular redox state and signalling. In part B of the study, 60 patients with IHD will be randomised to receive atorvastatin 40mg/d (n=30) or placebo (n=30) for 7 days before their bypass operation. The effect of atorvastatin treatment on endothelial function will be examined by ultrasound in the brachial artery. The effect of atorvastatin on redox signalling (O2- and ONOO- radicals) and inflammatory pathways in myocardium, vascular wall, and human adipose tissue will also be evaluated. This will be the first study examining the effects of atorvastatin on redox state and the activation of redox-sensitive pathways in vascular wall and myocardium of patients with IHD. This study may provide the basis for the design of new clinical trials examining the effect of statins on clinical outcome of patients with IHD.

Keywords: health sciences,cardiology,clinical pharmacology,physiology
Potential role of the histonemethylase SMYD3 in myogenesis (SMYD3 AND MYOGENESIS)

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: Italy
Call:  (FP7-PEOPLE-2007-4-3-IRG, 2007)
Start date: 2008-09-03
End date: 2012-09-02
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

SMYD3 is a histone methylase that di- and tri-methylates histone H3 at lysine 4. In normal conditions SMYD3 is highly expressed only in skeletal muscle and testis. We hypothesize that SMYD3 plays an important role in transcriptional regulation throughout myogenesis. We will use C2C12 myoblast and primary satellite cells as model systems to assess the contribution of SMYD3 to the transcriptional regulation of muscle specific genes. We will over-express and knock down SMYD3 to determine the impact of SMYD3 on the expression of myogenic markers and the ability of C2C12 cells to fuse into multinucleated myotubes. We will also determine functional mechanisms that account for a potential involvement of SMYD3 in myogenesis by employing chromatin immunoprecipitation experiments. Moreover, we will identify SMYD3 target genes in muscle cells by RNA microarray analysis and by the combination of the chromatin immunoprecipitation technique with massively sequencing technology (ChIp-seq). A further objective of the project will be to gain insights into the mechanisms underlying SMYD3 activity and its modulation, by exploiting in vitro and in vivo approaches.

Keywords: biological sciences,molecular genetics,molecular biology,transcription,chromatin,epigenetics,differentiation,myogenesis,histones methylation