Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Synthesis and characterization of Mn-Ln polynuclear complexes with interesting magnetic properties by the use of diol type ligands (MN-LN SMMS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Cyprus
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2012-01-01
End date: 2015-12-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Nanoscopic magnetic materials are of increasing interest because of their potential use for ultrahigh – density information storage, quantum computing, sensing and biomedical applications. Among the various types of nanoscopic magnetic materials, single molecule magnets (SMMs) represent a family of promising, for use in the above mentioned technological applications, molecule – based magnetic materials. SMMs are molecular transition-metal clusters that retain their magnetization below a blocking temperature (TB or Tcritical) in the absence of an applied field. In order to employ molecule-based materials in technological applications it is important to prepare SMMs with larger thermodynamic barriers (U) and effective (kinetic) barriers (Ueff) to magnetization reversal and the synthesis of polynuclear heterometallic Mn/lanthanide (Ln) species seems an attractive approach for achieving this. The main idea behind this approach is to combine Mnn+ and Ln3+ ion’s significant spin and/or their large anisotropy to generate Mn/4f SMMs distinctly different from, and superior to, the homometallic ones. The specific scientific and technological objectives of this project include: 1) the preparation of new Mn-Ln-L (L = diol-type ligands) clusters and SMMs, 2) the development of new synthetic procedures to polynuclear Mn-Ln clusters and SMMs, and 3) the complete structural and magnetic characterization of the compounds. The complete magnetic and structural characterization of the compounds is essential in order to rationalize their magnetic properties on the basis of their structural characteristics and finally to achieve optimization of their SMM properties by performing controlled structural modifications.

Keywords: single-molecule magnets,mn-ln heterometallic compounds,magnetic properties,crystal structures
From Theory of Mind to Vicarious Perception (TMVP)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Belgium
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2011-11-01
End date: 2015-10-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

We attribute mental states to others all the time: if I know that my wife wants diamonds for her birthday, or that my daughter knows how to open her bedroom door, this may influence my actions. Our the ability to attribute mental states – beliefs, desires, wishes, etc – to others, which is known as ‘theory of mind’, is taken to be the central concept in understanding how we are trying to make sense of others: how we engage cognitively with other agents. Some important questions about ‘theory of mind’ are: (i) Do non-human animals have theory of mind? (ii) How does theory of mind develop in ontogeny? (iii) What mental processes make theory of mind possible in humans? (iv) What are the neural underpinnings of theory of mind? I argue that the emphasis on theory of mind is a methodological mistake and that the empirical findings from developmental psychology and primatology point to a possible alternative, vicarious perception. We very often experience objects as affording actions to us: we experience an apple as edible or as affording eating. Importantly, sometimes, we experience objects as affording actions not for ourselves, but for someone else. Sometimes we see an apple as edible not for myself but for you. This is the phenomenon I call ‘vicarious perception’. Vicarious perception is a simpler, and more basic, way of engaging with others cognitively than theory of mind. I argue that while questions (i) – (iv) are difficult to tackle as long as they are about theory of mind, if we take them to be about vicarious perception, we get straightforward answers. More specifically, all experiments that are supposed to show that non-human primates have theory of mind in fact demonstrate that they are capable of vicarious perception. The same goes for the experiments about the theory of mind of less than 12 month old infants. If we shift the emphasis from theory of mind to vicarious perception, we can make real advances in understanding the origins of social cogni

Keywords: social cognition,philosophy,developmental psychology,cognitive ethology,primatology
Modulating EB protein interactions through small molecules (EB-SXIP)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2011-09-01
End date: 2014-08-31
Duration (months): 36.0
Total project cost (EUR): 75000.0
EU funding (EUR): 75000.0
Participants: 1
Project status: CLOSED

Microtubule plus-end tracking proteins (+TIPs) comprise a structurally and functionally diverse family of modular proteins that preferentially accumulate at microtubule (MT) growing ends. There, they regulate MT dynamics and mediate the anchorage of MTs to many other different cellular structures to control fundamental cellular processes including cell division, intracellular transport, cell adhesion and motility, and cell organization. +TIPs have a remarkable ability to form dynamic networks where most of the protein-protein interactions are mediated by End-Binding (EB) proteins. EBs are master regulators of all known +TIP networks; they are able to autonomously track MT tips independent of any binding partner while the rest of +TIPs generally require EB to efficiently track MT ends. Recently, a short linear sequence motif, denoted SxIP, used by numerous +TIPs for localization to MT ends in an EB-dependent manner, has been demonstrated to act as a general MT tip localization signal. The proposed research aims to obtain mechanistic insights into +TIP molecular recognition mechanisms and their modes of regulation, necessary to understand how +TIP dynamic and transient interactions translate into cellular functions. A major focus of the research project involves the identification of small-molecules that modulate these interactions and serve as a biological tool that allow the dissection with precise temporal control of the functional interplay between EBs and the broad number of proteins carrying a SxIP MT-tip localization signal. Furthermore, given the crucial role of this interplay in essential cellular processes, deregulated in neoplasia, such as MT-dynamics, mitosis or cell adhesion, and the proposed oncogenic roles of EB proteins, this research might also spur development of a new antitumoural therapeutic approach by blocking the EB-SxIP interaction.

Keywords: microtubules,+tips,end-binding proteins,chemical biology,structural biology,cell biology,small molecules,peptides,protein-protein interactions,therapeutics,cancer
Developing novel models of Amyotrophic Lateral Sclerosis using motor neuron cultures and zebrafish (NOVEL ALS MODELS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2011-10-01
End date: 2015-09-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

In 2008, I led a team that identified mutations in the TAR DNA binding protein (TARDBP) gene that encodes TDP-43 in ALS patients, which is enriched in inclusion bodies present in motor neurons from ALS patients. Also, mutations in the fused in sarcoma (FUS) gene were identified in ALS patients, with FUS involved in similar molecular mechanisms as TDP-43. This project aims to elucidate mechanisms involved in motor neuron degeneration caused by TDP-43 and FUS and to develop in vivo models to discover potential ALS therapies. Mutant TDP-43 causes degeneration in motor neurons from primary spinal cord cultures. Injection of mutant FUS in these cells will be conducted to determine if motor neurons are selective vulnerable to mutant TDP-43 or FUS. We also aim to characterize protein partners of mutant FUS/TDP-43 using immunoprecipitation and proteomic studies. Zebrafish is an excellent vertebrate model well suited for multigenic analysis and chemical screening in development and disease. Preliminary results suggest that knock-down of tardbp or fus as well as overexpression of mutant FUS and TDP-43 cause deficits in locomotory behavior and delayed axonal outgrowth in motor neurons from zebrafish. I am currently undertaking a multigenic analysis of TARDBP and FUS and previously ALS-related genes (SOD1, ALS2, VAPB) to discover whether common pathogenic pathways lead to motor neuron disorder. Finally, transgenic lines expressing mutant TDP-43 or FUS and fish lines with deletion of tardbp or fus genes are being generated and screened for motor neuron phenotypes. These lines will represent optimal ALS models to determine in vivo molecular mechanisms of pathogenesis. Further, our group is developing an automated platform in order to screen a large library of pharmaceutical compounds. This screen should propose compounds that are able to reverse the motor neuron specific phenotype in vivo and could be tested for therapeutically in ALS patients.

Keywords: health sciences,amyotrophic lateral sclerosis,motor neuron degeneration,neurodegenerative disorders,neurological diseases,zebrafish,motor neuron cultures,tardbp/tdp-43,fus,sod1
Ab initio Statics and Molecular Dynamics Simulation of Olefin Metathesis Catalysts for pharmacological purposes (COMPUTEDRUG)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2011-08-01
End date: 2015-07-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 2
Project status: CLOSED

The computational calculations nowadays do not act as a support element for supporting experimental results. Now we have taken more ambitious roles, going forward and saving time and money to the experimental sector. Thus we will tackle existing unexplained effects in olefin metathesis, including no stability, no or low activity, deactivation of the catalysts. By means of DFT, the design of more active catalysts will render the method of wider use as a tool for molecular assembly, rendering syntheses simpler and faster by reducing the number of required reactions to obtain the desired molecule, thus a reduction of the amount of waste produced too. The science outlined impacts the pharmaceutical world in numerous ways. Several quantum mechanics studies have been performed to rationalize the mechanism of olefin metathesis promoted by Ru-based catalysts. However, with the single exceptions of an old study on an oversimplified system, and 2-3 projects, all the computational results published to date have been obtained with static techniques. The dynamic studies are able to escape from the limits of our understanding of this important reaction. Half of the project is focused on an ab initio molecular dynamics simulation of Ru-catalyzed olefin metathesis. Taking advantage of the state-of-the-art ab initio molecular dynamics simulation CP2K package the dynamic characterization of the metathesis reaction pathway from reactants to products will be investigated. Free energy surfaces connecting the reactants to the Ru-metallacyclobutane key intermediate and finally to the products will be reconstructed from the simulations. Furthermore, simulations will be also performed to clarify the isomerization pathways that connect different reaction pathways corresponding to different geometric isomers of the catalyst, and usually labeled as side and bottom reaction pathways. From molecular dynamics, metadynamics and transition path sampling will be the chosen tools.

Keywords: health sciences,computational chemistry,reaction mechanisms ands dynamics,pharmacological sciences,pharmacy,quantum chemistry,modelling tools,inorganic chemistry,homogeneous catalysis
Perceptual Organization and Eye Movements (POEM)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Germany
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2011-09-01
End date: 2015-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The process by which the brain transforms visual input into coherent objects is called perceptual organization. State-of-art research in this domain does not offer much insight into the bridge between the realm of perceptual organization and information acquired by eye movements, which consist of fixations that are discrete and serial. The project proposed here, “POEM”, is designed to bridge this research gap by investigating the connection between Perceptual Organization (PO) and Eye Movements (EM) at three levels of processing: explicit (ePOEM), implicit (iPOEM) and functional (fPOEM). Regarding the methodology POEM will record the eye-movement pattern while the participants perform tasks based on perceptual organization of the carefully constructed stimuli shown in experimental settings in the lab. The information gathered will be analyzed by correlation analyses followed by modelling of the behavioural and eye-movement data. POEM will result in - information metrics at fixation points that are used by our visual system for PO, - an implicit measure for the strength of grouping factors based on EM data and - the description of the relationship between spatial aesthetics and the ease of navigation of EM to various “preferred” positions in a visual display. POEM is interdisciplinary- it deals with important open issues in perceptual psychology by using tools of the engineering domain. Additionally, its outcome will have tremendous interdisciplinary impact, especially in the domains of user-interface design, data-visualization and consumer psychology. Networking within POEM illustrates how the researcher will integrate, intensify and expand her collaborations with the USA and within the EU advancing the EU’s scientific excellence as well as her research career. In a nutshell, POEM comprises knowledge transfer into the EU, the introduction of a novel research approach and the long-term integration of an international renowned researcher in perceptual science.

Keywords: social sciences,psychology,visual perception,mid-level vision,perceptual organization,grouping,eye-movements,visual/spatial aesthetics,information metrics,saccade,scan-paths,fixation points
Systematic Identification and Validation of Epigenetic Cancer Lesions by Chemical Biology and Functional Genomics (EPICAL)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Austria
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2011-12-01
End date: 2015-11-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Epigenetic pathways contribute to cancer development and progression. These pathways act via proteins that modulate chromatin structure and gene expression, and can thereby give pro-proliferative and anti-apoptotic properties selected for in cancer. In total ~400 factors are known that either modify chromatin directly as epigenetic ‘writers’ (DNA methyltranserases, histone methyltransferases, acetyltransferases, kinases, ubiquitinases) and ‘erasers’ (histone demethylases, deacetylases, phosphatases, deubiquitinases) or indirectly by moving nucleosomes (‘remodelers’) or binding to the modifications set by the ‘writers’ (‘readers’; e.g. bromo, PHD, chromo, tudor domains). Small molecules inhibiting several chromatin modifying enzymes have been developed, and HDAC inhibitors and DNA methyltransferase inhibitors are approved drugs. While DNA methyltransferases and histone deacetylases are well-established drug-targets, the majority of the ~400 chromatin modifiers is not studied in cancer. Furthermore, the functional link between genetic alterations of the genes encoding these enzymes and increased proliferation in a cancerous state is less well established. Here we propose to generate and apply tools to systematically study these proteins in cancer using epigenome-wide knock-down studies and small molecule probes. This project directly benefits from the experience at the Broad Institute, where Stefan Kubicek worked for 3.5 years, which allowed him to bring to CeMM a library of knock-down constructs targeting all chromatin proteins in collaboration with the Broad RNAi platform. Similarly, his work on histone demethylases has yielded interesting probe compounds, and his continuing collaboration is recognized by his continuing status as a Remote Associate Researcher of the Broad Institute Chemical Biology Program. Stefan Kubicek started at CeMM in August 2010 and funding of this EPICAL proposal will allow to further integrate his career in the European research space.

Keywords: natural sciences,epigenetics,chromatin,functional genomics,small molecules,cancer
Biophysics of Reverse Transcription and its Inhibition (BIOPHYSRETRAIN)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Israel
Call:  (FP7-PEOPLE-2011-CIG, 2011)
Start date: 2011-09-01
End date: 2015-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

As the major target for therapy, Reverse Transcriptase (RT), and in particular the RT from the HIV virus, has been the subject of extensive research. However, despite an ever-increasing amount of information from traditional “bulk” studies, the detailed mechanisms of polymerization are still not completely understood. This is due, partially, to the stochastic nature of individual enzymes, which makes it impossible to follow more than one or two individual steps of polymerization using ensemble methods. I propose here to conduct a single-molecule, mechanistic study of HIV RT, by developing a high-resolution optical-tweezers, capable of resolving the individual polymerization and translocation steps of RT at a broad range of forces and nucleotides concentrations. Characterizing the dwell-time distribution at different experimental condition will allow us to study the complete mechano-chemical cycle of RT, its regulation by the template’s backbone-composition, structure and sequence, its interaction with additional viral and host factors, the molecular basis of inhibition by known inhibitors and the mechanism of resistance acquired through different mutations.

Keywords: molecular biophysics
Assembly and maintenance of a co-regulated chromosomal compartment (ACCOMPLI)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: Germany
Call:  (ERC-2011-ADG_20110310, 2011)
Start date: 2012-02-01
End date: 2017-01-31
Duration (months): 60.0
Total project cost (EUR): 2482770.0
EU funding (EUR): 2482770.0
Participants: 1
Project status: CLOSED

Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment. The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation. We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis. Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex.

Keywords: chromatin structure,chromosome,histone modifications,transcription,non-coding rna