Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Integrative Modeling and Engineering of Pseudomonas putida for Green Chemistry (PSEUDOMODEL)

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: Spain
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2013-06-01
End date: 2015-05-31
Duration (months): 24.0
Total project cost (EUR): 173370.6
EU funding (EUR): 173370.6
Participants: 1
Project status: CLOSED

The widespread use of fossil based fuels and plastics is a major cause of environmental pollution, and their production depends on limited non-renewable oil resources. The immense diversity of catalytic processes encoded in the genomes of sequenced organisms holds the promise of developing biotechnological systems for the efficient production of renewable energy sources and degradable materials via genetic engineering. However, the combinatorial possibilities for integrating enzyme-coding genes from different organisms into a microbial host cannot be explored systematically by classical approaches, which rely on the manual review of functional gene annotations. We propose to integrate a novel computational method for predicting combinations of genes facilitating efficient product yield with experimental approaches for genetic engineering. The method takes into account virtually all combinations of genes from sequenced organisms while avoiding the combinatorial explosion of their enumeration. We iteratively validate and refine the method by application to the genetic engineering of the well-characterised P. putida KT2440 for the production of polyhydroxyalkanoates, important precursors for biodegradable materials. Next, we apply the refined method to the solvent tolerant P. putida DOT-T1E for the production of n-Butanol, a promising next generation biofuel due to its high energy density, safe handling, and the possibility of direct use in gasoline motors. The interdisciplinary integration of theoretical and experimental research within the project is a promising approach for addressing the modern challenges in developing new biotechnological production systems. The project will lead to the discovery of engineered strains for the efficient production of biofuel and degradable materials, enabling novel industrial processes in green chemistry with the potential of alleviating environmental pollution and promoting economic independence from oil production.

Keywords: l211 computational biology,l811 genetic engineering - transgenic organisms,green chemistry,solvent tolerance,biofuel
Enantioselective Metal Enolate Alkylation Reactions Under Cooperative Lewis Base and Hydrogen-bond Donor (ENANTIOMEAR)

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-2012-IEF, 2012)
Start date: 2013-04-15
End date: 2015-04-14
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

The reaction between a metal enolate ion and an alkyl halide (or equivalent) electrophile is one of the most useful process for the formation of carbon-carbon bond in organic synthesis. We wish to develop enantioselective metal enolate alkylation reactions under cooperative Lewis base and Hydrogen-bond donor catalysis. The combination of Lewis basic H-bond donor and metal enolate ion to interact cooperatively to both activate and organise the enolate towards the electrophilic component, be it alkyl halide, Michael acceptor or anything else. During this Fellowship we wish to investigate this concept fully with the intention of discovering a new way of generating asymmetry in enolate alkylation reactions through the action of a chiral controller. Not only will these reactions constitute important developments in the field but the product structures are often biologically relevant, thus lending the chemistry to important synthetic applications. Accordingly the design and implementation of a new and broadly applicable methodology to solve the enantioselectivecatalytic alkylation reaction would have a significant impact on organic synthesis and is the focus of this proposal.'

Keywords: organic chemistry,catalysis,asymmetric synthesis,enantioselective reactions,metal enolate ion,alkylation reaction,lewis base,carbon-carbon bond formation
HumanRib: metal ion binding - stucture - function relations of the human CPEB3 ribozyme (HUMANRIB)

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: Switzerland
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2013-10-01
End date: 2015-03-31
Duration (months): 18.0
Total project cost (EUR): 144466.65
EU funding (EUR): 144466.65
Participants: 1
Project status: CLOSED

Until recently, ribozymes (enzymes composed of folded RNA) were found only in lower organisms. The discovery of the human CPEB3 ribozyme, related to the Hepatitis Delta Virus one, was an enormous breakthrough, which gave rise to numerous scientific questions. In the scope of this project, I want to answer the most emerging ones; I aim to solve the NMR structure of the whole CPEB3 ribozyme (we already have some promising preliminary results), as well as to crystallize it (in collaboration with another group) and compare the solution NMR and solid state X-ray structure. To understand changes in dynamics and folding of the ribozyme in the presence of Mg(II) (the natural cofactor), and also in the presence of other metal ions, single-molecule FRET (Förster Resonance Energy Transfer) experiments will be performed. As a long–term goal (after the repatriation to my home University), I will use NMR to characterize specific metal binding sites, structural and thermodynamic changes within the ribozyme upon the addition of metal ions. A big advantage of this project is that the ribozyme will be studied as a whole unit and not cut down into smaller parts. Although much more challenging, this will give a complete and clear view on the metal ion binding - structure - function relations. I am convinced that the proposed interdisciplinary project, which combines structural biology with coordination chemistry, is an exciting and necessary field of study, crucial for understanding not only the complicated structure and pathway of metal – mediated cleavage of the only known human ribozyme, but also for providing insight into its evolutional background, after being compared to the mechanism in which the viral HDV ribozyme functions.

Keywords: bioinorganic chemistry,metal ion binding - structure - function relations,metal - ribozyme interactions,rna structure,folding and dynamics,nmr,single molecule fret
Identifying molecular mechanism responsible for spatial reorganisation of the genome during embryogenesis (IMMRSRGE)

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-2012-IEF, 2012)
Start date: 2013-04-01
End date: 2015-03-31
Duration (months): 24.0
Total project cost (EUR): 231283.2
EU funding (EUR): 231283.2
Participants: 1
Project status: CLOSED

Spatial organisation in the nucleus is not random and it has a role in genome regulation. Large blocks of heterochromatin accumulate at the nuclear envelope and positioning of genes at the nuclear periphery correlates with gene repression. However, this organisation is not fixed and nuclear reorganisation has been described during mammalian development. In the inner cell mass of the blastocyst, chromatin exists in an unusual configuration with apparently widely dispersed open chromatin fibres. Following implantation at the epiblast stage, several hundreds of genes relocate to the nuclear periphery, concomitant with the formation of large domains of heterochromatin there. Interestingly, in the same time, specific genes can also remove from the nuclear envelope to the centre of the nucleus which is associated to their activation. Subsequently, lineage-dependant changes occur during the next steps of development. However, the molecular mechanisms which control this reorganisation are not understood. Prevailing models assume some transacting factors are responsible for an active recruitment and tethering of specific domains to the nuclear envelope. Thus, I propose, using a candidate approach and a RNAi screen, to identify factors responsible for the nuclear reorganisation observed in EpiSCs and to also address an alternative hypothesis that I have proposed and which involves a more passive accumulation of heterochromatin at the nuclear periphery that is influenced by nuclear pore complexes.

Keywords: nuclear reorganisation/embryogenesis/nuclear periphery/chromatin/rnai screen
Total Synthesis of Daphlongeranine B (DAPHNISYN)

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-2012-IEF, 2012)
Start date: 2013-03-01
End date: 2015-02-28
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

The Daphniphyllum alkaloids are a huge family of architecturally complex natural products found in evergreen trees and shrubs native to south-east Asia. To date, more than 200 members have been isolated and structurally characterised; some of them have been shown to possess interesting biological activity, such as cytotoxic- or antioxidative properties. However, not least due to their limited availability – both from natural sources and via chemical total syntheses – the biological functions and pharmacological properties of Daphniphyllum alkaloids have been only poorly studied until now. From an organic chemist`s point of view, members of the Daphniphyllum - family present highly attractive targets for synthetic approaches. Apart from their potential use as drugs or drug candidates, their fascinating, polycyclic skeletons present a vast playground to elaborate innovative synthetic strategies and tactics. Daphlongeranine B was isolated from the fruits of Daphniphyllum longeracemosum in 2007 and was shown to exhibit in vitro platelet aggregation. Its unprecedented hexacyclic core with seven stereogenic centres, three of which are fully substituted, presents a formidable and as yet unmet synthetic challenge. We are proposing the first total synthesis of Daphlongeranine B taking advantage of a series of partly unprecedented, powerful catalyst- and substrate controlled reactions and also cascade sequences. Their application will allow us to construct the target molecule in a nineteen-step route, starting from simple starting materials. Our proposed synthetic strategy features a novel tandem aminomethylation-alkynylation sequence, an unprecedented gold-catalysed 5-endo-dig hydroamination, a diastereoselective epoxidation followed by semipinacol rearrangement and a highly diastereoselective Michael-addition / Pd (0) catalysed vinylation cascade.

Keywords: total synthesis,natural products,daphniphyllum alkaloids,cascade reactions,asymmetric organocatalysis,semipinacol rearrangement
Exploring the ethical and social aspects of using mHealth technology in urban and rural home visitation programmes for women affected by domestic violence (DOVE)

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: United Kingdom
Call:  (FP7-PEOPLE-2012-IOF, 2012)
Start date: 2013-09-01
End date: 2015-08-31
Duration (months): 24.0
Total project cost (EUR): 265035.1
EU funding (EUR): 265035.1
Participants: 1
Project status: CLOSED

Domestic violence against women is highly prevalent and recognised as a global public health issue. Internationally there has been greater focus on the development and evaluation of interventions to address domestic violence in health care settings, paticularly primary and maternity care. To date, much of the evidence on health sector interventions to address domestic violence comes from the United States and there are few published studies in Europe. Futhermore, there are gaps in the research evidence with regards to domestic violence interventions in home visitation programmes for women with young children. In the USA, a team of researchers at the University of Virgina and John Hopkins University are testing a domestic violence intervention in home visitation programme using mHealth technology called eMOCHA DOVE (Domestic Violence Enhanced Home Visitation) in a five-year randomised controlled trial. The intervention will be tested in urban and rural sites in Baltimore and Virginia. This is the first study internationally to use mHealth technology to deliver a domestic violence intervention by home visitors. eMOCHA DOVE will assist home visitors in accurately identifying domestic violence and providing an intervention using a well tested empowerment model. The control group will receive the standard DOVE intervention which is adminstered by the home visitor using paper and pencil technique. The use of mHealth to deliver domestic violence interventions in health care and home visitation is new and warrants further investigation. It is not yet known whether mHealth will help or hinder the outcome of interventions for women and children. The fellowship provides an opportunity to conduct ethnographic research within a federally funded trial to explore the potential bioethical and social aspects with regards to issues such as safety, trust, impact on patient/provider relationship and communication and information sharing and confidentiality.

Keywords: s114 social studies of science and technology
HEteroblasty MOdelling: the TImetable of ONtogeny in Arabidopsis Leaves (HEMOTIONAL)

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-2012-IEF, 2012)
Start date: 2013-03-01
End date: 2015-02-28
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

The diversity of forms in nature raises questions on the mechanisms by which these forms originate. In many plant species, variations in leaf shape and size between juvenile and adult leaves accompany the acquisition of reproductive competence. This is termed heteroblasty. The canonical molecular pathway controlling heteroblasty has been recently described. It is topped by miR156, a miRNA which acts as a master switch to prevent the adult behaviour through the repression of transcription factors. However, the way how these genes control the growth patterns by which heteroblastic forms arise remains unknown. In this project, I propose to study the dynamics of heteroblasty establishment in Arabidopsis, by combining the knowledge acquired in molecular biology on the control of heteroblasty with the expertise on modelling of leaf growth in the host group (Prof. Enrico Coen and Prof. Andrew Bangham). Preliminary results suggest that the heteroblastic changes in leaf shape are ruled by the miR156 pathway until a certain leaf developmental stage, while the changes in leaf size are conditional on plant’s capacity to exploit its environmental resources. To test this hypothesis, I will i) use a modelling platform developed in the host group to compare quantitatively the early growth pattern of leaf 6 (adult) with the one of leaf 1 (juvenile), ii) develop an inducible line to analyze and model the spatiotemporal effects of the miR156 pathway in these early growth patterns, iii) modify the environment during leaf 6 development to analyze the plasticity of this leaf, and iv) analyze and disturb the expression of miR156 during leaf 6 development to question the involvement of the miR156 pathway in the control of final shape and size of this leaf. Through a combination of developmental, physiological and modelling approaches, this integrative analysis of heteroblasty will generate fundamental knowledge on leaf growth, a key target for breeding robust crops within a changing world.

Keywords: l211 computational biology,l310 developmental genetics - embryology in plants,l401 organ physiology,heteroblasty,leaf development,growth,modelling,mir156,arabidopsis thaliana
Deciphering the role of phenolic glycolipids in mycobacterial pathogenesis (PGLMP)

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: France
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2013-07-01
End date: 2015-06-30
Duration (months): 24.0
Total project cost (EUR): 194046.6
EU funding (EUR): 194046.6
Participants: 1
Project status: CLOSED

Mycobacterial diseases, like tuberculosis and leprosy, are still a threat for public health. Although antibiotherapy and BCG vaccine exist, they have failed to control these diseases. It is hence crucial to improve our knowledge of the factors involved in mycobacterial pathogenesis to design new therapies. The hallmark of mycobacterial pathogens is their ability to persist in the host by delaying the adaptive immune response. Among the mycobacterial factors suspected to play a role are phenolic glycolipids (PGL), which are produced notably by the major mycobacterial pathogens, including M. tuberculosis and M. leprae. PGL possess a common lipid core and species-specific saccharidic domains. However, the definitive proof of their role on immunomodulation is missing. In this project, I intend to investigate this issue and to identify the mechanism of action of PGL. I plan to use a novel strategy developed in the host laboratory based on the reprogramming of a biosynthetic pathway in BCG to make it synthesize species-specific PGL and to compare them in a similar relevant envelope. Using this tool, PGL from M. leprae was found to endow BCG with an increased capacity to exploit complement receptor CR3 for efficient invasion of phagocytes and evasion of inflammatory responses. To get insight into the structural basis, I propose to use a chemistry approach in which the various species-specific domains will be synthesized. The strength of this project is to combine my expertise in cellular microbiology with powerful approaches (recombinant BCG strains and synthetic PGL) to: 1) unravel the molecular mechanism of the interaction PGL-CR3 and its specificity by using different ligands; 2) identify other receptors for PGL; and 3) determine the signalling pathways involved in the immunomodulation by PGL. Besides to advance our understanding of the pathogenesis of major human diseases, I expect this work to open avenues for development of therapies against mycobacterial diseases.

Keywords: infection by mycobacterial pathogens,host-pathogen interaction,modulation of immune responses,cell signalling and receptors,lipidic pathogenicity factors
Assembling a functional map of axonal signalling endosomes (AXOTRANSMAP)

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-2012-IEF, 2012)
Start date: 2013-11-01
End date: 2015-10-31
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

The polarisation of neurons in somatodendritic and axonal compartments allows signal propagation over long distances. Despite the important role played by electrical signals, fast axonal transport is crucial for long-range communication between the soma and distal synapses, which is carried out by vesicular transport mechanisms. Neurotrophins and their receptors are internalised at axon terminals by clathrin-mediated endocytosis and conveyed by signalling endosomes to the soma, where they activate transcriptional responses regulating neuronal homeostasis and survival. However, little is known about the identity and the dynamics of the organelles involved. The aim of my project is to build a functional and physical map of axonal retrograde carriers in specific neuronal types, which are the target of important human diseases. For this purpose, I will exploit a new developed affinity purification strategy using the binding fragment of tetanus neurotoxin (HC) conjugated to monocrystalline iron oxide nanoparticles (MIONs). At different time points after internalisation, retrograde carriers will be magnetically purified and submitted to mass-spectrometry analysis. The kinetics of endosomal maturation will be assessed using quantitative label-free SILAC protocols. These results will uncover new components of signalling endosomes and identify dysfunctions of this pathway that are at the basis of motor and sensory neuropathies.

Keywords: retrograde axonal transport,neurotrophins,tetanus neurotoxin,signalling endosomes,mass-spectrometry,neurodegeneration