Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Mechanism of homology search during homologous recombination (MULTIPLE SEARCH)

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-2013-IOF, 2013)
Start date: 2015-02-01
End date: 2018-04-30
Duration (months): 36.0
Total project cost (EUR): 279780.9
EU funding (EUR): 279780.9
Participants: 1
Project status: CLOSED

Homologous recombination is a mechanism by which DNA double-strand breaks are faithfully repaired using the sequence information present on an intact duplex DNA. The efficiency of this mechanism is crucial for cell survival, and its accuracy is of prime importance for genomic stability. Although being the signature reaction of homologous recombination, the search for homology performed by the broken molecule coated with the Rad51 recombinase (called the “nucleoprotein filament”) is poorly understood: how a single entity is able to scan the megabases of the genome to rapidly find its unique homologous target remains a mystery. My post-doctoral project aims at tackling this long-standing "needle-in-a-haystack" problem. For this, I introduce new concepts and approaches to elucidate how this potent search takes place in a massive excess of competitor DNA. First, we hypothesize that several sections of the nucleoprotein filament are able to sample different duplex targets at the same time. This multiplexed search process by the nucleoprotein filament will be studied in vitro and in vivo. In particular, I will develop a technique derived from chromosome conformation capture to isolate and quantify “multiple invasions” performed by the nucleoprotein filament in vivo. Second, I intend to identify the functional substructure of the nucleoprotein filament, which is not a simple homogeneous assembly of Rad51 along the single-stranded DNA. Instead, it embeds other proteins, like the translocase Rad54 and the Rad51 paralogs, which exert a positive role on homology search through still unknown mechanisms. In particular, I will study how these proteins participate in the rapid rejection of pairing to heterologous molecules. Third, I will study the processing of the “multiple invasions” intermediate, and the potential threat it represents for genomic stability. This study will provide unprecedented insights into the key mechanism of homology search during homologous recombination.

Keywords: homology search,recombination,rad51,rad54,rad51 paralogs,multiple invasions
Decoupled Insulator-Supported Molecules (DECIMOL)

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-2013-IEF, 2013)
Start date: 2014-05-01
End date: 2016-04-30
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

The DECiMOL (DECoupling Insulator-supported MOLecules) project exploits complementary real- and reciprocal space spectromicroscopy techniques to develop key insights into the correlations which exist between electronic structure, interaction forces, and geometry of molecules adsorbed on thin insulating layers on silicon. This understanding is mandatory in areas such as molecule-based information processing or optoelectronic devices. DECiMOL will specifically aim at investigating the transition in binding situation of the deposited molecules depending on the insulator thickness as well as the molecular functionalisation by inspecting molecular properties and explore the capability to locally change the geometric or electronic state of the adsorbed molecules. Most importantly, DECiMOL will study the efficacy of decoupling molecules from semiconductor, rather than metal surfaces, via a thin insulating films by using a combination of three experimental techniques – namely scanning tunnelling microscopy (STM), dynamic force microscopy (DFM, also known as non-contact atomic force microscopy), and photoemission spectroscopy (PES). The experimental approach will be supplemented by density functional theory (DFT) calculations. Within DECiMOL, the researcher will be trained in using PES and DFT methods, which form an important complimentary approach to his previous STM and DFM based work.

Keywords: molecular adsorption,insulators,insulating thin films,atomic force microscopy,photoelectron spectroscopy,molecular electronics,electronic structure,molecular bond formation
Improving Performance and Cost of Content Delivery in a Hyperconnected World (CDN-H)

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: Germany
Call:  (FP7-PEOPLE-2013-IOF, 2013)
Start date: 2014-08-01
End date: 2017-07-31
Duration (months): 36.0
Total project cost (EUR): 349047.2
EU funding (EUR): 349047.2
Participants: 1
Project status: CLOSED

The Internet has become the predominant channel for innovation, disruption, and for creating new revenue streams. In a hyperconnected world a substantial fraction of the global population spends more and more time online to work, for shopping and entertainment, and to get access to information. We are observing an unprecedented amount of content generated by human activity and popular application such as web browsing, video streaming, and social networks that has to be delivered to the hundred of millions of Internet users around the globe. To cope with the always increasing demand for content, a number of Content Delivery Networks (CDNs) have been developed to deliver voluminous amount of content, that originates from content producers, to hundred of millions of Internet users around the globe. CDNs greatly extend the capabilities of the Internet by deploying massively distributed infrastructures to accelerate content delivery. Today, CDNs are responsible for almost half of Internet traffic. Operation at that scale poses challenges for CDNs as they have to dynamically map end-users to appropriate servers without being fully aware of the network conditions within an Internet Service Provider (ISP) or the end-user location. CDNs also try to minimize their operation cost. Moreover, ISPs struggle to cope with rapid traffic shifts caused by the dynamic server selection policies of the CDNs. In this project we develop systems and study the necessary incentives to turn the challenges, in terms of performance and cost, that content delivery stakeholders, including CDNs and ISPs, face separately into an opportunity for collaboration. We also re-examine the fragile economic model of the Internet and provide methodologies to study the trade-offs between peering cost and performance for content delivery. Finally, we propose a radical approach to push CDN functionality at the edges to deal with today's complex and personalized content in a scalable and cost-efficient manner.

Keywords: content delivery,internet,computer networks
Macromolecular Ion-Solvent Interactions in Charged Droplets (MISICD)

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: United Kingdom
Call:  (FP7-PEOPLE-2013-IIF, 2013)
Start date: 2014-06-30
End date: 2016-09-08
Duration (months): 24.0
Total project cost (EUR): 309235.2
EU funding (EUR): 309235.2
Participants: 1
Project status: CLOSED

We use computational and analytical methods to study the factors that determine charge state of macromolecules in droplet, gaseous and bulk environments and the relation of the charge state to the conformations of the macromolecules. Practical applications of the study are found in electrospray mass spectrometry (ESMS), which is an analytical technique used for the analysis mainly of biological molecules such as proteins, DNA, poly-saccharides. To understand the processes that take place in electrospray ionization, knowledge of the charging and the conformations of a macromolecule is required in bulk, droplet environment and gaseous state.The factors that determine the charge state distribution of the macromolecules in the droplet include the interactions between the analyte and the solvent in the droplet environment, acidity changes in the droplet, evaporation rate of the solvent vs. deprotonation rate of the macroions in the droplet, release mechanisms of macroions from droplets, and details in the operation of the electrospray instrument. We use advanced molecular simulation methods to study rare molecular fluctuations in the solvent and macromolecules that are central in describing quantitatively the above processes. These rare fluctuations are captured by methods for study activated processes in statistical mechanics. The study aims at understanding fundamental processes in the charging of macromolecules and laying the theoretical foundation for processes that give rise to the signals in the ESMS methods. The computational methodology that we develop for the sampling of the conformational changes can be used in a broader class of problems than those we study. Moreover, our studies in the gas-droplet and bulk environment will enhance our knowledge on the interactions that determine the conformations of biological macromolecules.

Keywords: molecular simulations,activated processes,dynamics,stability of charged droplets,conformational changes,disintegration mechanisms,molecular dynamics,monte carlo methods,charge state,solvation
Multiwavelength cell spectroscopy to define the pathophysiology of mitochondrial disorders in living cells. (CELLSPEX)

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: United Kingdom
Call:  (FP7-PEOPLE-2013-IIF, 2013)
Start date: 2014-03-01
End date: 2016-02-29
Duration (months): 24.0
Total project cost (EUR): 309235.2
EU funding (EUR): 309235.2
Participants: 1
Project status: CLOSED

Mitochondria are the powerhouses of eukaryotic cells. Through oxidative phosphorylation (OxPhos), mitochondria extract energy from nutrients and use it to transfer protons across a proton-impermeable membrane creating a proton motive force to drive ATP production. Since the enzymes that catalyse OxPhos are encoded in both the mitochondrial and nuclear genomes, mutations in either one can cause mitochondrial disease, with a minimum prevalence of 1 in 5,000 live births in the EU. The molecular-biochemical causes of mitochondrial disorders and their clinical manifestations are highly diverse, but the most common defects are in complex I, the first enzyme of the OxPhos system. Currently, the mechanisms linking specific complex I mutations to OxPhos failure, cell and tissue damage, and ultimately disease, are poorly understood – precluding development of rational, evidence-based, therapies. The paucity of tools available to define mitochondrial function in the living cell is a major hindrance. During my research in the United States, I have developed optical instrumentation, technology and expertise capable of defining the bioenergetic status of mitochondria in living cells, with an exquisite level of accuracy, under tightly defined conditions. Every bioenergetic parameter that impacts on OxPhos function is accessible, including the redox potential of both substrates of complex I, the proton motive force, and the flux. Here, I propose to transfer my unique instrumentation and expertise in cellular bioenergetics to the Mitochondrial Biology Unit in Cambridge, UK, and integrate them with existing projects on molecular and clinical aspects of mitochondrial disorders, in order to link the biochemical definition of complex I dysfunctions with the characterization of their consequences in vivo, provided by my technology. This integrated approach will allow us to bridge fundamental gaps in knowledge, and drive forward the development of effective clinical therapies.
The role of MAGE proteins in mitochondria: Novel insights for the regulation of neuronal function (MITONEUROMAGE)

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: Greece
Call:  (FP7-PEOPLE-2013-IEF, 2013)
Start date: 2014-04-01
End date: 2016-03-31
Duration (months): 24.0
Total project cost (EUR): 168794.4
EU funding (EUR): 168794.4
Participants: 1
Project status: CLOSED

The Melanoma Antigen (MAGE) genes received increasing attention due to their roles in human diseases, mainly cancer and neurodevelopmental disorders. The family includes over 25 genes in humans, characterized by a MAGE homology domain (MHD). TypeI subfamily contains 3 gene clusters, which are silent in normal tissues, except in male germ cells and placenta. TypeII subfamily contains un-clustered genes, expressed in embryonic and adult tissues, especially in the nervous system. TypeII proteins are involved in neuronal function and two of their members, Necdin and MAGEL2, are part of the locus that is invariably deleted in patients of the neurodevelopmental Prader Willi Syndrome. Yet, understanding their functional repertoire has been impeded in mammals by redundancy between the numerous members. We identified a unique homologue of the MAGE family in the nematode C. elegans, and named it MAGE-1. Our preliminary data indicate that MAGE-1 is a mitochondrial protein highly expressed in neurons and intestinal cells, and required for maintaining mitochondrial integrity and dynamics. Notably, re-examination of Necdin in the mouse revealed that it partially localizes to the inner membrane of mitochondria in neurons. In addition to identifying novel components regulating mitochondria in neurons, our findings suggest that mitochondrial dysfunction may underlie pathologies associated with loss of function of MAGE proteins. The proposal is structured around 3 aims: 1. Characterize the role of MAGE-1 in C. elegans; 2. Identify binding partners and signaling pathways of MAGE-1 in mitochondria; 3. Characterize the role, pathways and partners of Necdin in mitochondria of mammalian neurons. The expected results will enhance our understanding of the evolutionary relationships of MAGE genes, and will reveal and characterize novel functions for mammalian MAGE proteins, such as Necdin, providing fresh insight into the pathology of the associated neuronal diseases.

Keywords: mage family proteins,mitochondria,prader-willi syndrome,neurons,metabolism,c. elegans,neurodevelopmental disorders
Dissecting the Mechanism of Nucleosome Retention in Mouse Spermatozoa (NUCLEOSOME RETENTION)

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-2013-IEF, 2013)
Start date: 2015-03-01
End date: 2017-06-16
Duration (months): 24.0
Total project cost (EUR): 207928.8
EU funding (EUR): 207928.8
Participants: 1
Project status: CLOSED

Studies in mice and men suggest that changes in environmental conditions such as nutrition, exposure to environmental pollutants or parental care during early postnatal life can affect the development, physiology and fitness of offspring. The epigenetic mechanisms underlying the transmission of such traits over one or multiple generations are largely unknown but DNA methylation, RNA and nucleosomes have been proposed as mediators of such inheritance. At the end of male germ cell development chromatin is extensively remodeled, resulting in a highly compact nuclear architecture in spermatozoa that is compatible with fertilization. During this process, most but not all nucleosomes are removed and replaced by protamines. The host laboratory recently demonstrated retained nucleosomes localize at CpG islands of the genome that are present within regulatory regions of genes, suggesting that these regions may confer epigenetic inheritance between generations. Preliminary data implicate different histone H3 variants and modifications in the nucleosome eviction and retention process. Here I aim at dissecting the mechanism of nucleosome retention in mouse sperm. Using a quantitative biochemical approach, I will test the possibility that nucleosome retention at CpG islands is an indirect consequence of high intrinsic affinities of protamines for GC-poor DNA. I will determine the composition of evicted versus retained nucleosomes in terms of histone variants and post-translational modifications, by performing immunoprecipitation coupled to mass spectrometry. Importantly, I will investigate whether nucleosome retention is controlled by a “retention factor” using a mass spectrometry approach combined with cellular and genetic assays. The proposed research will provide mechanistic insights into the mechanisms of nucleosome retention during spermatogenesis, thereby laying the foundations for further functional studies in nucleosome-based paternal epigenetic inheritance.

Keywords: chromatin remodeling,nucleosome retention,histone h3 variants,spermatogenesis
The origins of gestural imitation: insights from evolution, development and cultural transmission (GESTRANSCULT)

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-2013-IEF, 2013)
Start date: 2015-04-01
End date: 2017-03-31
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

The ability to copy others lies at the heart of our capacity to learn languages, social rules and acquire material culture. While imitation is a core feature of human life, understanding how it evolved, how it develops and the role of cultural transmission are not fully understood. Moreover, most of our understanding comes from studies of tool use, while neglecting the role of imitation in other contexts, namely communicative interactions, such as gesture. Considering the key role gesture itself plays in human communication and in language evolution, understanding the mechanisms underlying gestural imitation is thus essential for assessing how human culture and communication relate. The aim of this project is to conduct a multi-dimensional investigation of gestural imitation from evolutionary, developmental and cultural perspectives. Combining these complementary angles provides a richer understanding of how communication and culture relate, how they evolved and develop and how transmission processes influence them. To examine the evolution of gestural imitation, the Fellow will examine whether bonobos, an understudied species of great ape, can copy a novel gesture. From evolution to ontogenetic development, the Fellow will next examine the development of gestural imitation by comparing children’s imitation of gestures versus technical actions. Finally, recent research shows that transmission processes shape the structure of language and technologies and so the Fellow will explore how cultural transmission (a form of imitation) shapes gestural structure using diffusion chain experiments. Different types of gestures will be compared to test whether transmission shapes signal structures in language-like ways. The Fellow’s expertise in ape communication complements the Scientist in Charge’s specialism in cultural cognition. Mobility to the UK enables her to consolidate and extend her expertise, to acquire new training and to contribute cutting edge research to the ERA.

Keywords: gestural imitation,cumulative cultural evolution,bonobo,development of imitation,over-imitation,diffusion chain,language evolution,chimpanzee,cultural cognition,cultural transmission
Reintroducing Stone and Mortar Movements, Materials, Methods and Motivations of Builders and Patrons in Early Medieval England, Switzerland and Italy (RESTOMO)

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-2013-IEF, 2013)
Start date: 2014-09-01
End date: 2016-08-31
Duration (months): 24.0
Total project cost (EUR): 309235.2
EU funding (EUR): 309235.2
Participants: 1
Project status: CLOSED

In the Early Middle Ages stone architecture was reintroduced to many parts of European by secular and ecclesiastical authorities who recruited building specialists from distant regions. This project will analyse how and why this radical change from wood to stone architecture took place by investigating the movements, materials, methods and motivations of builders and patrons. Previous research has focused on texts and objects. For example, Bede speaks of workmen from "Francia" building Wearmouth abbey. There in Wearmouth are also remains of mechanical mortar mixers, an archaeological feature that is known from numerous sites between Naples and Newcastle. The best-known group of expert builders, the so-called “magistri commacini”, is connected to historical sources (e.g. "Leges Langobardorum") and finds (e.g. S-Z-styli) as well. Turn of the first Millennium Rodulfus Glaber sees the world clad in a “white mantle of churches” by building activity. In this project, this traditional approach will be complemented and contrasted using a GIS-based analysis of the historic landscape and building materials in three selected regions where previous scholarship offers excellent foundations for new research: England, Switzerland, and Italy. At the regional scale, the research will examine geomorphologic conditions and natural resources in relation to travelling routes, settlement patterns and density of population in the Early Middle Ages. This will create a clearer picture of the respective living and working conditions of the building specialists as well as the resources, connections and intentions of their employers. The stone buildings had influence on the way people experienced the landscape as well as the inside of the buildings enabled them to new ways of visual and aural impressions. Even before that, change could be percieved with the setting up of the building site.

Keywords: early middle ages,archaeology,history of building,building in stone,craftsmen,guilds,landscape archaeology,medieval monasteries,royal palaces,mortar mixer,styli,magistri commacini,bede