Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Influence of Streptococcal virulence factors on host autophagy regulation. (GASAUTOPHAGY)

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: Germany
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2013-05-01
End date: 2015-04-30
Duration (months): 24.0
Total project cost (EUR): 168794.4
EU funding (EUR): 168794.4
Participants: 1
Project status: CLOSED

Group AStreptococcus (GAS) is a predominant Gram-positive bacterium causing a substantial burden of diseases in humans. Autophagy is a starvation-induced response that provides nutrients by degrading long-living proteins and recycling intracellular organelles. In 2004, autophagy was identified as a new immune mechanism for killing and clearing invading GAS in epithelial cells. It is regulated by host proteins such as Beclin1, ATG 5, ATG6 and LC3. On the other hand, host proteases such as calpain, caspase and cathepsin inhibit autophagy activation by degrading these proteins. GAS virulence factors that can affect host autophagy have never been identified or described so far. The first part of this proposal will focus on the GAS virulence factors that can initiate degradation of host autophagy proteins. Potential GAS virulence factors listed in this proposal are Streptolysin S (SLS) and Streptolysin O (SLO) which are playing a role in host protease activation. Streptococcal Pyrogenic Exotoxin B (SpeB) and Group A streptococcus protease (SpyCEP) are also going to be investigated for their potential to directly degrade host autophagy proteins. Degradation of host proteins involved in autophagy, by these proteases can influence autophagy regulation. The second part of this proposal is aiming to study the role of autophagy in zoonotic streptococci infection. As increasing numbers of invasive infection caused by zoonotic streptococci are recently reported, this would be a first and an important study. The third part will be to study the role of autophagy in bacterial killing in neutrophils. Neutrophils are known to be one of the most important immune cells to clear GAS infection. However the role of autophagy in neutrophils against GAS infection has never been studied. The understanding of mechanisms underlying autophagy regulation by GAS has the potential to contribute towards the discovery of targets for novel therapeutic agents against GAS infections.

Keywords: lif group a streptococcus autophagy protease bacterial protein
Probing the sequence determinants of ion channel voltage sensing via computation: towards the design of custom-tailored voltage-sensing modules (VOLTSENS)

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: Switzerland
Call:  (FP7-PEOPLE-2012-IOF, 2012)
Start date: 2013-05-01
End date: 2016-04-30
Duration (months): 36.0
Total project cost (EUR): 264112.5
EU funding (EUR): 264112.5
Participants: 1
Project status: CLOSED

Voltage sensing is a crucial property for a variety of proteins involved in many physiological functions (selective ion transport through membranes, enzymatic catalysis…). All these proteins achieve voltage sensing through the action of a 4 alpha-helix bundle module called the voltage-sensor domain (VSD). This transmembrane module achieves its function thanks to specific features, such as the presence of a large number of conserved charged or hydrophobic residues isolating the intracellular domain from the extracellular one. Despite these common features, nature achieves a surprising variability in terms of voltage-sensing properties, i.e., the thermodynamic and kinetic properties characterizing VSD activation span a wide range of values among the VSD superfamily. What are the residues responsible for such modulation and how this variability is achieved is not yet understood and is of great interest from a medical perspective, as it would shed light onto the effect of disease-involved mutation of crucial residues (channelopathies). This proposal offers to use the arsenal of computational methods derived from theoretical chemistry (molecular dynamics simulations using atomistic and polarizable force fields, free energy calculations, QM/MM calculations, force matching algorithms…) and bioinformatics (homology modeling, evolutionary modeling…) to unravel this question. The proposal unfolds in three steps: the first involves developing a robust framework to evaluate the thermodynamic and kinetic properties of activation of a specific VSD. The second consists in evaluating the impact of the mutation of specific residues on the parameters determined in step 1, while validating and refining the theoretical framework through comparison of these results to experimental ones from our collaborators. The final step consists in integrating this data in an evolutionary model including a variety of VSDs.

Keywords: c115 theoretical and computational chemistry,p219 biophysics,l210 bioinformatics,l101 molecular biology and interactions
Comparative Archaeological Study of Egyptian Predynastic Settlements (CASEPS)

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: 2013-09-01
End date: 2015-10-01
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

Over the last 40 years, archaeological investigations in Egypt, often promoted and undertaken by European research teams, have gained a considerable amount of new data about the formative stage of ancient Egyptian civilization, known as the Predynastic (c. IV millennium BC). Nevertheless, several key areas and issues, crucial for furthering our understanding of the mechanisms that gave rise to this early civilization, still remain obscure: Predynastic settlement' chronological and functional variability; how the process of state formation influenced the life of the inhabitants of the Nile Valley; dynamics of interaction between different cultural spheres extant in Egypt at this early stage. This project seeks to shed light on these issues by using: (i) new unpublished archaeological data from two of the most significant Predynastic sites (Naqada and Hierakonpolis), whose long history covers also the important stages of state formation and consolidation in Egypt; (ii) modern methodologies and approaches, poorly exploited or never applied to this research field, so far (e.g. quantitative, statistical and spatial analyses; intra- and cross-regional comparative approach; use of models and concepts from anthropology and the social sciences). A better comprehension of the mechanisms that gave rise to the ancient Egyptian civilization will also have a value at a global archaeological level, providing a source of comparisons and contrasts for early civilizations in other world's regions. A project's by-product will be a digital archive of standardized and comparable archaeological datasets, that may be used and form a point of reference for future research. The execution of the project at the UCL's Institute of Archaeology will provide the researcher with access to unparalleled expertise in the area of Egyptian archaeology, anthropological archaeology, advanced scientific training in the field of computing and statistics and their application in archaeology.

Keywords: s401 archaeology,s402 prehistory and protohistory,egyptology,egyptian predynastic,settlements,state formation,material culture,statistics,spatial analysis,anthropology,social sciences.
PROTEOMICS BASED IDENTIFICATION OF BIOMARKERS AND CLEAVAGE PRODUCTS IN PANCREATIC CANCER USING GLYCO-CAPTURE TECHNOLOGY (GLYCOMARKER)

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: Germany
Call:  (FP7-PEOPLE-2012-IIF, 2012)
Start date: 2014-02-01
End date: 2016-01-31
Duration (months): 24.0
Total project cost (EUR): 161968.8
EU funding (EUR): 161968.8
Participants: 1
Project status: CLOSED

In cancer biology, primary tumours and metastasis are embedded in a microenvironment comprised of cells such as tumour associated macrophages and cancer-associated fibroblasts. Tumour and stroma derived cytokines form a paracrine loop of mutual activation, often resulting in elevated tumour aggressiveness. Interestingly, numerous studies have shown that altered protein glycosylation is a hallmark event of carcinogenesis. In many cases, tumour progression is accompanied by several parameters which include changes in the extent of glycosylation of proteins as well as the carbohydrate structure, increased level of blood glycoproteins as well as altered glycosylation of cell surface glycolipids, membrane-associated glycoproteins and secreted glycoproteins. Both N- and O-glycosylated glycoproteins have been shown to be modified in a wide range of cancers and hence have potential as novel biomarkers for detection and surveillance of the disease. Thus, it is not surprising that many existing cancer biomarkers (e.g. Her2/neu in breast cancer, CA125 in ovarian cancer, prostate specific antigen (PSA) in prostate cancer, CEA and CA 19-9 in colorectal cancer) are glycoproteins. Despite the recent advancement in the biomarker discovery tools, however, to date the glycoproteome has not been extensively studied and thus used to mine potential biomarkers due to technical complexity. The characterisation of a glycoprotein as a biomarker for monitoring of tumour growth as well as cancer progression has the advantage that both the protein and glycan moieties contain valuable information. Together with host institute, I aim to develop novel methods for the capture/enrichment and thus identification of cancer-associated glycoproteins from pancreatic cancer cells. This approach will allow us to uncover pivotal proteolytic processing events of cell surface and secreted proteins, which further highlights the importance and elucidate the regulation of tumor-stroma interactions.

Keywords: proteomics,glycoproteins,pancreatic cancer,degradome,secretome,biomarker
The evolution of the Grassland biome: exploring past events to predict future scenarios (GRASSLANDS)

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-2012-IIF, 2012)
Start date: 2013-08-01
End date: 2015-07-31
Duration (months): 24.0
Total project cost (EUR): 231283.2
EU funding (EUR): 231283.2
Participants: 1
Project status: CLOSED

Knowledge of the evolution of the grassland biome throughout the Earth's environmental history is important for the reconstruction of links between diversification/extinctions events and climate. Biomes are now being impacted by anthropogenic environmental change on an unprecedented scale, and one mean of understanding how component species will react is to study the effects of past environmental changes. Hence, understanding the evolutionary history of grassland ecosystems in the context of past biotic and abiotic changes is relevant to the way we will manage them under future environmental change. A new perspective on the history of the grassland biome is beginning to emerge from key developments in palaeontology and molecular phylogenetics that will be integrated interdisciplinary and multidisciplinary in the present project for the first time. GRASSLANDS aimed at understanding the timing and nature of grasslands' most important components, the grass (Poaceae) and daisy (Asteraceae) families, through the combination of fossil data, molecular phylogenetics and computational approaches. The potential contribution of GRASSLANDS to our understanding of the evolutionary history of these families and grassland ecosystems in general is significant and will certainly provide new insights into the rise of flowering plants as the dominant components of almost every terrestrial ecosystems.

Keywords: l805 conservation biology - ecology - genetics,l803 systems evolution - biological adaptation - phylogenetics - systematics
Finding the Ghost in the Genome: Assessing the contribution of epigenetics to environmental plasticity in the soil sentinel Lumbricus rubellus (EPIWORM)

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: 2013-09-01
End date: 2015-08-31
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

It has been established that the epigenetic landscape (cytosine methylation, histone modification and non coding RNAs) impacts on the underlying genomic architecture thereby regulating the transcriptional machinery and modifying gene expression. These elegant mechanisms of control influence tissue differentiation, organism life spam and can coordinate biochemical pathways responses to stressors such as UV light and elevated metal ion concentrations. It is the aim of this project to test the overarching hypothesis that: “Alterations in the epigenetic landscape caused by exposure to environmental contaminants directly modulate the expression of specific genes increasing phenotypic plasticity and providing the mechanistic basis underpinning the organism’s responses to the stress inducing causative stimuli.” We will test this hypothesis using, the epigeic earthworm L. rubellus, establishing it as a model to study the interactions between the environment and the epigenome. The experiment plan is designed to derive a causative relationship between modifications in the epigenome and the ability of an organism to tolerate specific environmental challenges. The project will primarily exploit metals/metalloids (Ni & As) with a mechanism-of-action with postulated impact on the epigenome, but the wider aim is to establish a new paradigm between the epigenetic landscape and the environment. The training programme will put great emphasis on exploring the opportunities provided by next generation sequencing technologies and the rich genomic resource provided by our target organism. This will require training in the technical, bioinformatics and informative frame works that will enable the production of a refined physical map of the earthworm epigenomic landscape. The training will exploit an established network of national and international partnerships with the primary goal of establishing the proposed fellow as a research leader in their own right.

Keywords: dna methylation,histones,mirna,earthworms,v307 environmental toxicology,v309 systems evolution - biological adaptation - phylogenetics - systematics,l208 epigenetics and gene regulation
Progenetic evolution in the deep-sea fauna (PRODEEP)

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: Norway
Call:  (FP7-PEOPLE-2012-IIF, 2012)
Start date: 2013-11-01
End date: 2017-09-17
Duration (months): 24.0
Total project cost (EUR): 216034.2
EU funding (EUR): 216034.2
Participants: 1
Project status: CLOSED

The proposed 2-year project conducted at the University Museum of Bergen (Norway) will address the questions on the evolution of the deep-sea fauna. It will focus on the group of predominantly deep-sea polychaete worms from the subfamily Hyalinoeciinae with worldwide distribution, remarkable diversity at great depths, and possible progenetic origin. The project will study the morphology, taxonomy and phylogeny of hyalinoeciin polychaetes and will evaluate the role of progenesis within Hyalinoeciinae in their successful colonization of the deep sea. The project will be based on the unique and extensive collection of the deep-sea hyalinoeciins appropriate for the DNA analysis and will also utilize materials from a number of European research institutions. It will combine the methods of traditional taxonomy with the state of the art molecular techniques. This study aims to: (1) assess the morphological and genetic variation within Hyalinoeciinae; (2) assess the phylogenetic position of Hyalinoeciinae species with suggested progenetic origin; (3) trace the evolution of characters within Hyalinoeciinae; (4) develop a hypothesis on the possible pathways of the deep-sea invasion by hyalinoeciins. The expected results will: provide taxonomical revision of hyalinoeciins; advance understanding of genetic and morphological variation in polychaetes from various depth zones; advance knowledge in polychaete phylogeny; and contribute to understanding of the role of progenesis in the deep-sea fauna formation and evolution. The project will be among the first studies of evolutionary processes within deep-sea polychaetes, one of the dominant groups of organisms inhabiting soft-bottom deep-sea communities, and will significantly strengthen European excellence and competitiveness in this area of marine studies. The project with facilitate the establishment of mutual collaborative links between the deep-sea scientists in Norway, Germany, the UK and Russian research community.

Keywords: v309 systems evolution - biological adaptation - phylogenetics - systematic,v302 biodiversity - comparative biology,v304 conservation biology - ecology - genetics,v306 environmental and marine biology
Ultrafast energy transfer and dissipation in electronically excited materials: calculations from first principles (ULTRADEX)

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-2012-IIF, 2012)
Start date: 2013-05-01
End date: 2015-04-30
Duration (months): 24.0
Total project cost (EUR): 183504.6
EU funding (EUR): 183504.6
Participants: 1
Project status: CLOSED

The development of ultrafast experimental techniques with femtosecond time resolution is driving the need for deeper theoretical understanding of how intense optical excitation can alter the interatomic forces, drive atomic motion and effect structural changes in materials. The main objective of this project is to extend the scope of electronic structure computational methods, allowing us to quantitatively simulate (without phenomenological parameters) the coupled electronic and atomic dynamics in highly photoexcited materials on a picosecond and sub-picosecond timescale. We will use these new methods to calculate the transfer of energy from electronic states to the lattice vibrations in photoexcited GaAs and to follow the redistribution of vibrational energy through to its ultimate thermalisation in the lattice. We will compare our predictions of electronic distributions and vibrational motion with those measured by our collaborators, using time-resolved photoemission and x-ray diffraction, allowing us to benchmark the effectiveness of our theoretical approach. The understanding of energy relaxation and transfer following optical excitation underpins a variety of technologically important processes: e.g. the ultrafast response of optically active components in high-speed telecommunications and, in the field of renewable energy, the initial stages of photocatalysis or optical absorption in solar cells. To support advances in these areas, it is important to develop predictive methods for modelling the behaviour of optically excited materials at an atomic level on very short time scales. In delivering these predictive methods and by the virtue of the applicant's expertise in electronic structure theory and the emerging field of ultrafast electron and phonon dynamics, this project will enhance EU scientific excellence and competitiveness.

Keywords: electronic structure theory,p205 electronic properties of materials and transport,p206 lattice dynamics,p207 semiconductors,ultrafast science
Sensory feedback in the development of motor cortex: underlying physiological network mechanisms and its relation to epileptic discharges (MOTOR_DEV)

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: 2013-05-01
End date: 2015-04-30
Duration (months): 24.0
Total project cost (EUR): 194046.6
EU funding (EUR): 194046.6
Participants: 1
Project status: CLOSED

Early in development, spontaneous bursts of activity at the level of the spinal cord trigger spontaneous twitches of corresponding groups of muscles fibres. Twitching provides sensory feedback that generates specific neuronal oscillations in somatosensory cortex. The proposed project will address, in first line, if sensory feedback provided by spontaneous muscle twitches evokes specific patterns of neuronal activity in motor cortex. This could occur via functional projections arising from somatosensory cortex and/or thalamic nuclei, which have been demonstrated in adults. These activity patterns will be studied as substrates for the development of motor cortex, and their developmental changes will be characterized in relation to the formation of its main output, the corticospinal tract, and developmental twitching elimination. In addition, the proposed project will address if under pathological conditions, spontaneous muscle twitches trigger epileptic discharges in motor cortex. It is anticipated that such discharges are asymptomatic prior to, but are manifested by epileptic jerks upon the formation of the corticospinal tract. Using a combination of cutting-edge electrophysiological and imaging techniques, in vivo, the results are expected to provide the first insights on if and how peripheral stimuli induce the expression of neuronal oscillations in the developing motor cortex, and on how this may guide its maturation. Moreover and of great clinical importance, the results will provide a mechanistic explanation for the phenomenon of electroclinical uncoupling in neonatal epilepsy.

Keywords: systems neuroscience,brain development,neonatal,sensorimotor systems,behaviour,physiological twitches,cerebral cortex,thalamus,neuronal oscillations,brain imaging,electrophysiology,epilepsy