Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Regulating TGF-beta signalling at the transcriptional level and in cancer (TGF-BETA AND CANCER)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2007-2-1-IEF, 2007)
Start date: 2008-06-11
End date: 2010-06-10
Duration (months): 24.0
Total project cost (EUR): 233785.15
EU funding (EUR): 233785.15
Participants: 1
Project status: CLOSED

To understand, treat, cure and ultimately prevent cancer we must first be able to understand the basic mechanisms that regulate normal cell growth. One of the cellular factors involved both in normal development and in malignant transformation is transforming growth factor b TGFb. TGFb is a multifunctional cytokine which, in addition to cancer is also implicated in developmental disorders, fibrosis and autoimmune diseases. TGFb signalling has been implicated in both tumour suppression and progression. Although TGFb inhibits inhibits growth of early carcinomas, later in tumourogenesis, it can induce an epithelial-mesenchymal transition (EMT), promoting an invasive, metastatic tumour phenotype. TGFb signals through the activation of Smad proteins. After activation, Smads accumulate in the nucleus where they regulate transcription, either positively or negatively. Although some recent advances have been made, exactly how Smads regulate transcription and how in turn the Smads are regulated during transcription is still remains unclear. The first aim of this application is to investigate which components of the transcriptional machinery get recruited to the active promoters after TGFb stimulation. In order to achieve this an siRNA library screen targeting histone modifying enzymes and chromatin remodelling proteins will be performed. As mentioned above TGFb has growth inhibitory effects, which are counteracted by Smad7, a negative regulator of the pathway. Although Smad7 has not been identified as an oncogene to date, a genome-wide association screen of tag SNPs performed by our collaborator, has implicated Smad7 as being highly correlated to colorectal cancers. The second aim of this application is to reveal the molecular mechanisms behind this correlation. As colorectal cancers are the second most prevalent malignancy in Europe, understanding how Smad7 affects this process may have wide implications both for the treatment, as well as for the screening of the disease.

Keywords: cell biology,molecular biology,tgf-beta,smad,transcription,chromatin,colon cancer,oncology,population genetics
The role of dopamine and novelty in decision-making in humans: behavioral and neuroimaging studies (DA AND DECISIONS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2007-2-1-IEF, 2007)
Start date: 2008-07-01
End date: 2010-06-30
Duration (months): 24.0
Total project cost (EUR): 169390.93
EU funding (EUR): 169390.93
Participants: 1
Project status: CLOSED

Decision-making involves evaluating the costs and benefits of available options for action. Many psychiatric disorders involve a disruption of decision-making processes. Application of concepts derived from instrumental learning theories, computational models, and fMRI (functional Magnetic Resonance Image) technology has allowed identification of key neuronal substrates of these processes. A key control influence is mediated by dopamine transmission, vie its modulatory influences on the striatum and prefrontal areas. Work using experimental animals has drawn an accurate picture of the neuronal mechanisms that regulate dopamine transmission including an important effect elicited by novelty. The objective of the project is to deepen in the understanding of the behavioral and neurological interrelationships of dopamine neurotransmission, novelty processing and decision-making in humans. To achieve this goal we will use computational models in conjunction with brain imaging technologies, specifically fMRI and MEG (Magnetoencephalograpy). In a first step, we will address the human brain’s response to different aspects of novelty and how this is mediated by dopamine. In a second step we will focus on the effect of different kinds of novelty in decision making during probabilistic gambling from a behavioral and brain imaging perspective. Finally, in a third step we will try to understand the effect of pharmacological manipulations upon probabilistic decision making from a behavioral and neurobiological perspective. Results obtained within this project will inform how humans make decisions under uncertainty, and how novelty influences choice behaviour. Understanding how critical brain computations are implemented in the human brain will also inform an understanding of psychiatric disorders where aberrant novelty processing may reflect a fundamental component such as attention deficit disorder (ADHD).

Keywords: neurosciences,neuropsychology,brain research,dopamine,novelty,neuroanatomy,probabilistic gambling,computational models,reinforcement learning,decision-making.
System biology of nitrogen-carbon-signal integration in the overall Arabidopsis signaling network. (ATSYSTM-BIOL)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Outgoing Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2007-4-1-IOF, 2007)
Start date: 2008-10-01
End date: 2011-06-30
Duration (months): 33.0
Total project cost (EUR): 193036.39
EU funding (EUR): 193036.39
Participants: 1
Project status: CLOSED

Plant development is under the control of abiotic environment. Nitrogen (N) and Carbon (C) signaling are well known to interact together, but also with a set of diverse signaling pathways including light and the plant hormones, auxin or cytokinin. Relationships of C/N “balance” with these “growth factors” are hypothesized to trigger the regulation of broad developmental processes such as root/shoot development or flowering. The overall aim of this proposal is to use a genomics and systems biology approach to design and explore an experimental space to test how the intersection of light, carbon, nitrogen and hormone signaling pathways acts to coordinate responses of gene networks in Arabidopsis. Combinatorial Design will be used to select a set of treatments designed to broadly cover the experimental space of interactions using a minimal number of treatments, as described in Lejay et al 2005, and whole genome responses will be assayed using Affymetrix Gene Chips. The work flow includes: Aim 1. Design and test the entire experimental space of treatments using reporter gene constructs, to aid in selection of an optimal CD set for transcriptome analysis. Aim 2. Integrate & analyze transcriptomic data in the context of Arabidopsis multinetworks to identify regulatory gene networks whose expression is controlled by the interaction of these different signals on gene regulation. This analysis will allow us to identify “hub”-genes involved in coordinating gene network responses to N/C/Light/Hormones signals. Aim 3. Validate the gene regulatory networks by classical reverse-genetics concerning “hub”-gene and to place these molecular actors into previously identified gene networks. This project will mark a significant and useful turn in my scientific experience to genomics, biocomputing and systems biology.

Keywords: natural sciences,biological sciences,plant system biology,computational science,genomics,signalling pathways
Generalized complex 4-manifolds (GC4M)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Netherlands
Call:  (FP7-PEOPLE-2007-2-1-IEF, 2007)
Start date: 2009-06-01
End date: 2011-05-31
Duration (months): 24.0
Total project cost (EUR): 157831.18
EU funding (EUR): 157831.18
Participants: 1
Project status: CLOSED

We will study a notion of Lefschetz pencils for generalized complex 4-manifolds, aiming at results analogue to those of Donalson and Gompf in symplectic geometry stating that a 4-manifold has a symplectic structure if and only if it admits a Lefschetz pencil. To achieve the desired results we have to find the right definition of a Lefschetz pencil in the generalized complex setting. Earlier work of the candidate on this area has already shed some light into this question. We will study the question of how to adapt Seiberg—Witten theory in order to produce differential—topological obstructions for a 4-manifold to admit a generalized complex structure. This should mirror Taubes' result relating SW-invariants and symplectic structures. Work of Bauer and Furuta should provide the springboard for this part of the project. On the physical side, we will study mirror symmetry on generalized complex manifolds. The work on Lefschetz pencils will provide us with a number of generalized complex manifolds described in terms of singular torus fibrations, therefore an ideal place where to study mirror symmetry in the setting of SYZ. For these torus fibrations, there is a locus on the base where one of the circles forming the torus fiber collapses. In other models where this occurs, one describes the mirror as a Landau—Ginzburg model. Therefore this raises the questions about what Landau—Ginzburg models are for generalized structures.

Keywords: lefschetz pencils,generalized complex structures,seiberg--witten invariants,mirror symmetry
Inorganic Polyphosphate: Synthesis and Functions, relationship with Inositol Polyphosphates (POLYPHOSPHATE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2007-2-1-IEF, 2007)
Start date: 2009-07-01
End date: 2011-06-30
Duration (months): 24.0
Total project cost (EUR): 236620.21
EU funding (EUR): 236620.21
Participants: 1
Project status: CLOSED

Cellular regulation by soluble inositol phosphate messengers has yielded surprising knowledge that reaches well beyond the rigorously characterized regulation of Ca2+ release by inositol 1,4,5-trisphosphate (IP3), the best-known inositol phosphate. Inositol pyrophosphates belong to the diverse family of inositol polyphosphate species that have a range of signaling functions. The best-characterized inositol pyrophosphates are diphosphoinositol pentakisphosphate (IP7) and the bis-diphosphoinositol tetrakisphosphate (IP8). The activity of inositol pyrophosphates appears to be related to their rapid turnover in cells and also to their pyrophosphate groups, considered to contain high-energy bonds and unique signaling molecules implicated in regulation of processes, including apoptosis, telomere maintenance or vesicular trafficking. Inositol phosphate signaling molecules can directly mediate protein phosphorylation, a new way in which signals can be transduced in cells. Another phosphate molecule, inorganic polyphosphate (poly P), found in every living-cell, is a chain of many tens or hundreds of phosphate residues linked by the same phosphoanhydride bonds as in ATP. Poly P likely was a phosphorylating agent and catalyst of peptide bond formation in prebiotic times. It has been shown that poly P is essential in stringent response, survival for bacterial responses to stresses, starvation and pathogenesis. Yeast mutants, affected in enzymes of the inositol pyrophosphate synthesis have reduced intracellular poly P levels suggesting that inositol pyrophosphates are necessary for poly P synthesis and maintenance. The mechanism by which inositol pyrophosphates are able to transduce the cellular phosphate status into a cascade of signaling events is unknown. The present proposal tries to find links between inositol polyphosphate and poly P in relation to poly P synthesis and their role in cell signaling.

Keywords: health sciences,phosphate,polyphosphate,unositol polyphosphate,pyrohosphate,cell signaling
Gravitational Effective Field Theories and Microscopic Description of Superradiance (GRAVEFTMICS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2007-2-1-IEF, 2007)
Start date: 2009-02-01
End date: 2011-01-31
Duration (months): 24.0
Total project cost (EUR): 161792.99
EU funding (EUR): 161792.99
Participants: 1
Project status: CLOSED

Effective Field Theory (EFT) techniques provide an invaluable theoretical tool for dealing with scale hierarchies in Particle, Nuclear and Condensed Matter Physics. EFT is the best technique for extracting predictions from non-renormalizable quantum field theories. In this proposal we will explore the application of EFT techniques to General Relativity in order to probe the low-energy limit of Quantum Gravity. EFT should provide reliable predictions for low-energy results that any consistent theory of Quantum Gravity must reproduce. Within this approach we will discuss emission power of gravitational radiation and rotating Kaluza-Klein black holes in extra dimensional spacetimes and quantum particle production in inflationary universes, which have not been successfully addressed by standard methods. The gauge/gravity correspondence provides a microscopic description of black hole evaporation due to Hawking radiation. Hawking radiation is closely related to superradiant scattering from rotating black holes, in which the amplitude of a scattered wave is greater than that of the incident wave. The second aim of this proposal is to understand the gauge/gravity description of superradiance, and the related "ergoregion instability" of certain rotating systems without horizons. This is an ambitious proposal that fits the objectives of the FP7 Marie Curie action: the researcher will reinforce his present integration in Europe after spending two years abroad. He will not merely continue his past research work. He will make an ambitious, but smooth and consistent, transition to a new area of research. Thus, he will have advanced scientific training in new multi/inter-disciplinary fields and in complementary skills. He will benefit from the network of collaborations of Harvey Reall and DAMTP/Cambridge, and will integrate and reinforce a European research network. In the end, the chances of getting a senior position are considerably enhanced.

Keywords: quantum field theory,gravitation,effective field theory,quantum gravity,black holes,gravitational radiation
Discovery of molecular markers for the inverse relationship between platinum and taxane resistance in cancer (CISTAX)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Ireland
Call:  (FP7-PEOPLE-2007-4-2-IIF, 2007)
Start date: 2008-10-01
End date: 2010-09-30
Duration (months): 24.0
Total project cost (EUR): 185736.25
EU funding (EUR): 185736.25
Participants: 1
Project status: CLOSED

Abstract Aim: To identify a gene and protein expression pattern associated with platinum resistance and taxane sensitivity in a panel of drug-resistant cancer cell lines. Background: Despite the success of early detection programs and surgical techniques for the treatment of cancer many patients will still require chemotherapy. Initial responsiveness to chemotherapy is high, however the majority of patients ultimately relapse with resistant disease. This research proposal will examine resistance to two commonly used classes of chemotherapy, platinums and taxanes. When cancer cells become resistant to platinum chemotherapy they often become sensitive to taxanes and vice versa. This inverse relationship happens in all cancer types and the mechanism of this relationship is not understood. Research Project: This project will study gene and protein expression in a large panel of drug resistant cell lines in an attempt to understand the mechanism of the inverse resistance relationship between platinums and taxanes. This process will discover a set of molecular markers predicting the inverse relationship between platinum and taxanes. These have the potential to be translated to the clinic and be used to identify patients likely to respond to platinum or taxane chemotherapy. Outcomes: The success of research projects like the one described in this application have the potential to revolutionise cancer therapy by individually tailoring chemotherapy. This will significantly increase the response rate of both platinum and taxane chemotherapy as it will allow the identification of patients likely to respond to treatment. Patients identified as being resistant to both agents could then be treated with alternative chemotherapy. The understanding of the mechanism of the inverse resistance relationship may also reveal new targets for cancer therapy.

Keywords: anticancer therapy,platinum,taxane,resistance,sensitivity,drug resistant cell models
High Energy Interactions: From Colliders to Cosmic Rays (C2CR)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Norway
Call:  (FP7-PEOPLE-2007-2-1-IEF, 2007)
Start date: 2008-06-01
End date: 2010-05-31
Duration (months): 24.0
Total project cost (EUR): 279239.42
EU funding (EUR): 279239.42
Participants: 1
Project status: CLOSED

The years 2007 and 2008 will mark the completion of the Pierre Auger observatory and the start of the Large Hadron Collider (LHC) at CERN, respectively. Whereas the former has been built to uncover the sources of ultra-high energy cosmic rays, the latter is designed to test the Standard Model of particle physics. In both experiments, the use of Monte Carlo (MC) models to describe hadronic interactions is essential. In CR experiments, the measured properties of extensive air showers can be connected to the properties of the primary particle only via hadronic MC models. At present, the poorly known interaction models prevent a reliable determination of the primary type and its energy. Thus, an improvement of present day CR interaction models is an important and urgent task. This improvement will become possible soon, since the LHC experiments will deliver for the first time a experimental data in the kinematical region important for CR experiments. This projects aims to use these data to test and to develop further the existing QGSJET simulation. It is planed to include into QGSJET nonlinear interaction effects, to generalize the model to photo- nuclear interactions, and to account for higher twist QCD effects. Apart from its importance for a reliable extrapolation towards the very high CR energies, such a development will have an interdisciplinary aspect, opening the way for numerous applications in the collider physics. A self-consistent model like QGSJET that allows one to calculate within the same scheme total and diffractive cross sections, and to treat various hadronic final states, can be applied in collider experiments both for the general studies of hadronic interactions, and for more dedicated as, e.g., diffractive jet production. Thus the aim is to develop QGSJET to a truly universal simulation, able to describe collider data from LHC as well as to contribute to a more reliable determination of the primary type and its energy in UHECR experiments.

Keywords: quantum field theory,astrophysics
Constructing an Artificial Enzyme for Olefin Metathesis (AEOM)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Switzerland
Call:  (FP7-PEOPLE-2007-4-2-IIF, 2007)
Start date: 2008-03-01
End date: 2010-02-28
Duration (months): 24.0
Total project cost (EUR): 179297.73
EU funding (EUR): 179297.73
Participants: 1
Project status: CLOSED

The introduction of stable and selective catalysts for olefin metathesis (OM) has considerably simplified the construction of double bonds. Herein we propose to tackle two areas of the OM reaction that have received little attention. First, we will address selectivity problems in an important type of OM reaction: metathesis cross-coupling or simply cross metathesis (CM). Second, we will examine the potential applications of OM in chemical biology. OM has no biological counterpart and therefore it may be possible to do metathesis chemistry in the biological milieu without affecting endogenous cellular processes. Although seemingly incongruent goals, both are attainable within the framework of this proposal because of the special nature of the metathesis catalysts we propose to develop: artificial metathesis enzymes. We propose to endow a protein with an OM active-site. A highly modular proteinaceous secondary ligand sphere will allow the use of recombinant molecular biology techniques to generate new ligands for the metathesis catalyst; in this way a large number of catalyst structures can be generated in a short time. The family of catalysts can then be tested in metathesis reactions that are difficult to perform selectively, such as cross metathesis. A hallmark of enzymes is the exquisite selectivity they often display for their substrate, and we believe this can be harnessed in the context of OM to solve many of the current selectivity problems. A second focus of the research will be the application of the metathesis enzyme as a tool for chemical biology. Since there is no biological analogue of OM, it may be possible to use metathesis to tag biomolecules in vivo. Moreover, a protein derived ligand would allow for selective localization in vivo through the selection of an appropriate protein tag.

Keywords: enzimology,olefin metathesis,enzyme engineering,organometallic chemistry,homogeneous catalysis