Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Deciphering the dynamics and molecular mechanisms of APC/C activity in vitro and in live cells (APCACTIVATION)

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: 2014-01-01
End date: 2016-01-31
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

The spindle assembly checkpoint (SAC) inhibits chromosome segregation and mitotic exit prior to biorientation of all chromosomes on the mitotic spindle by restraining the activity of the anaphase promoting complex or cyclosome (APC/C) towards Cyclin B1 and Securin. In contrast, other APC/C substrates like Cyclin A2 bypass this inhibition and are degraded in the presence of an active SAC. Despite its central role in mitotic progression, the molecular mechanisms activating the APC/C towards different substrates are poorly defined. Here, I present a research plan that aims to decipher the dynamics and molecular mechanisms of APC/C activity in live cells and in vitro. Specifically, I will establish an assay to quantify the spatial and temporal dynamics of APC/C-dependent ubiquitylation in live human cells by Foerster resonance energy transfer (FRET) between endogenously tagged Cyclin B1 and ubiquitin. In parallel, I will reconstitute the APC/C in vitro from recombinant proteins and quantify ubiquitylation activity of the reconstituted complex using fluorescently labelled substrates to assess the function of individual APC/C subunits, cofactors and posttranslational modifications. Together, the results obtained in live cells and in vitro will substantially advance our understanding of the molecular mechanisms that govern mitotic progression in human cells.

Keywords: mitosis,spindle assembly checkpoint (sac),anaphase promoting complex/cyclosome (apc/c),quantitative live cell microscopy,in vitro reconstitution
Quantum Resolution of Gravitational Singularities (QM-SING)

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-2012-IEF, 2012)
Start date: 2013-10-01
End date: 2016-03-02
Duration (months): 24.0
Total project cost (EUR): 183469.8
EU funding (EUR): 183469.8
Participants: 1
Project status: CLOSED

String Theory is a promising theory of quantum gravity, unifying all known forces. However, it is notoriously hard to extract testable predictions from it. Black holes are ubiquitous in string theory (and any theory of General Relativity (GR) for that matter). Their study offers a shortcut for successfully testing the validity of string theory. This projects pursues a theoretical test of string theory, through the study of black holes. In classical GR, black holes are solutions with enigmatic properties, such as a spacetime singularity. When coupling them to quantum fields, there appear questions that GR cannot explain: the information paradox, black hole entropy. In this project, we will answer these issues by studying black hole microstates. Their existence would resolve the black hole singularity, solve the information paradox and explain black hole entropy. For supersymmetric black holes, which are rather unrealistic, there has been quite some success in constructing these microstates, but not nearly enough to solve all black hole problems. We plan as a first step in the string theory test to systematically construct (1) new supersymmetric black hole microstates, and (2) take the story further to more realistic, non-supersymmetric radiating black holes. A later stage of this research will be to determine their properties. Additionally, the implications on cosmological singularities will be intitiated, with the expertise of the GRAPPA Institute (Gravitational AstroParticle Physics Amsterdam), affiliated with the ITFA, training the researcher in a new field (cosmology). In addition, the researcher will supervise master students, coach graduate students and lecture graduate courses in an international school. Furthermore, he will present his work in leading international conferences, and develop research management skills. This complete and intensive training will greatly enhance the researcher's abilities to lead a research group in the future.

Keywords: p101 fundamental interactions and fields,p111 relativity,high energy physics,string theory,supergravity,general relativity,black holes
Association between influenza virus RNA polymerase and the transcriptional machinery of the host cell (FLU-POLII)

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: 2014-04-01
End date: 2016-03-31
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

Influenza infections represent a worldwide problem both in terms of public health and economic consequences. Seasonal influenza epidemics affect 3 to 5 million people annually and are estimated to cause 250,000-500,000 deaths globally. Besides, recurrent pandemics are a serious threat because novel viruses can emerge to which the population has no pre-existing immunity. In the event of such a situation, existing vaccines would be unlikely to be effective and production of a vaccine matching the pandemic virus would require several months. In addition, existing antiviral treatments are very limited and development of resistance by the virus would reduce their effectiveness. Thus, there is clearly an urgent need to develop new treatments for the control of influenza. The viral RNA polymerase is at the core of the transcription and replication complex of influenza virus and it is a crucial factor for pathogenicity and host restriction. Its activity is regulated by interactions with the host cell. Previous research in the host group has shown that the viral polymerase interacts with cellular RNA polymerase II (Pol II), but many aspects of this interaction remain unclear and its biological role is not known. This project will explore this interaction under the hypothesis that it is required for synthesis of viral mRNA. We will map the Pol II-binding domain of the viral polymerase. If the interaction is not direct we will identify the mediating factor(s) using proteomic approaches. The functional significance of the association between viral polymerase and Poll II will be investigated in vivo using a combination of reverse genetics and ChIP-sequencing approaches. This project is expected to identify novel druggable targets where essential interactions between the viral machinery and host cell factors can be disrupted, which may ultimately lead to the development of new antiviral drugs against influenza infection.

Keywords: l608 virology,l101 molecular biology and interactions,l203 proteomics
Effects of individual heterogeneity on stochastic population processes: the case of nonbreeders. (NONBREEDERS)

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: 2013-08-12
End date: 2016-08-11
Duration (months): 36.0
Total project cost (EUR): 282561.0
EU funding (EUR): 282561.0
Participants: 1
Project status: CLOSED

Successful population management depends on our ability to predict future patterns of population abundance and extinction. This requires a clear understanding of the mechanisms underlying population dynamics. In this project I will integrate mathematical, statistical and ecological approaches to provide new understanding of effects of individual heterogeneity on the stochastic dynamics and genetics of populations. I will achieve these objectives by developing and analyzing new stochastic population models that incorporate both random and nonrandom differences among individuals, specifically focusing on the role of nonbreeders in driving population processes. I will then use two long-term datasets on wild bird populations (Green-rumped parrotlets and European shags) to parameterize these models and quantify the impact of nonbreeders on key population processes and extinction risk. Nonbreeders are often present in wild populations, but are routinely ignored when predicting population dynamics, potentially introducing errors into management recommendations. In this project, I will therefore provide new theoretical and empirical advances and quantify their potential impact on management decisions. I will spend two outgoing years at the University of California, Berkeley, working with world-leading scientists in avian population ecology, statistical ecology and theoretical demography to learn and develop new methods of stochastic modeling and ecological data analysis. By combining these new skills with my existing expertise in mathematical biology, I will build an unusual skill set that is currently in high demand. I will bring this expertise back to a leading European research university, the University of Aberdeen, where my ability to link the disciplines of ecology and mathematics will allow me to forge new research initiatives and achieve new understanding of impacts of individual heterogeneity on population dynamics, thereby advancing European research excellence.

Keywords: v107 population dynamics,v305 ecology,v308 population biology - population dynamics - population genetics,v304 conservation biology - ecology - genetics,theoretical ecology
Role of Adipose DPP4 Deletion in Diet-Induced Obesity (ADDIO)

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: 2013-07-01
End date: 2015-06-30
Duration (months): 24.0
Total project cost (EUR): 168794.4
EU funding (EUR): 168794.4
Participants: 1
Project status: CLOSED

Dipeptidyl peptidase-4 (DPP-4) is an exoprotease that cleaves N-terminal dipeptides from several substrates such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GLP), impairing the function of the incretin system, which is of key importance for glucose homeostasis. Indeed, DPP4 inhibitors are currently in clinical use for type 2 diabetes. The host group has described for the first time that DPP4 is secreted by adipose and strongly correlates with adipocyte volume and parameters of the metabolic syndrome and is decreased to the lean level after weight reduction in humans. Moreover, novel data obtained in the host group suggest that DPP4 may impair insulin sensitivity in an auto- and paracrine manner. Thus, DPP4 arises as a novel adipokine potentially linking obesity to the metabolic syndrome. Since there is a growing interest in anti-diabetic therapies based on DPP4 inhibition, a deeper understanding of the role of adipose DPP4 on the onset and progression of insulin resistance is needed. This project aims to explore the impact of adipose DPP4 deletion in diet- induced obesity (ADDIO). For this purpose the host group is generating an adipose-specific DPP4 knockout mouse to prove a causal role of this protein in the development of the metabolic syndrome. Our global aim will be pursued following a 3 step strategy: Firstly, we will assess the impact of adipose DPP4 genetic deletion by characterizing the metabolic phenotype of adipose-specific DPP4 knockout mice. We will next determine the impact of genetic deletion of adipose DPP4 on the development of diet-induced impaired glucose tolerance and insulin resistance. Finally, we will explore the mechanism responsible for the potential protective/delaying effect of adipose DPP4 genetic deletion on impaired glucose tolerance and insulin resistance in obesity.

Keywords: dipeptidyl peptidase-4,adipose tissue,insulin resistance,type 2 diabetes
The European Union and the Legal Protection of Marine Biodiversity in the Arctic (EURO-ARCTIC LAB)

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

The current laws for the protection of marine biodiversity in the Arctic are weak and fragmented and are insufficient to ensure the implementation of an ecosystems approach, which is necessary for the preservation of biodiversity (CoP Biodiversity Convention, 2000 and 2002). The Euro-Arctic LaB project will establish what powers the European Union (EU) has to pursue its stated objective of protecting marine biodiversity in the Arctic (COM (2008) 763 final; JOIN (2012) 19 final) and will establish how the EU can best use these powers to help generate an effective legal system for the protection of marine biodiversity in the Arctic. The project’s aims will be met through establishing a) the extent to which the EU has competence to shape the development of international law on the protection of marine biodiversity in the Arctic and b) the best route to pursuing the development of international law. During the past 4 years, the European Commission (COM (2008) 763 final), the Council of the European Union (Council conclusions on Arctic issues, 8 Dec 2009), the European Parliament (2009/2214 (INI)) and the High Representative have declared that the EU will be more engaged in Arctic issues. There is however a lack of literature that thoroughly assesses the EU’s current and potential action. This project is therefore appropriate to examine the EU’s competence and practice. It will also provide insights on the effectiveness of the EU’s action at the international and regional levels. The completion of this project will contribute to the preservation of Arctic marine biodiversity for its intrinsic worth and also for the many ecosystem services it provides including supporting sustainable fisheries as well as leaving the resources in place for future scientific study and potential use in pharmaceuticals and other industries. The findings will also help illuminate the development of EU international policy more generally.

Keywords: arctic,european union,european union external relations,law of the sea,international environmental law,marine biodiversity,biodiversity
Herbivore induced plant defences: the evolution and genetic basis of their specificity (INDUCED DEFENCE)

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: 2013-07-01
End date: 2015-06-30
Duration (months): 24.0
Total project cost (EUR): 161968.8
EU funding (EUR): 161968.8
Participants: 1
Project status: CLOSED

Herbivore induced defence is widespread in plants and are likely to be species-specific. The specificity has been suggested to be mediated by herbivore associated elicitors (HAE), however, how such specificity evolved and what are the underlying genetic bases are little understood. Species of genus Nicotiana offered a suitable system to address these questions, because they distributed in great range of variation in habitat and evolved various specialized defence traits against herbivore. In this project, firstly, I will pursue the question how specificity of herbivore induced defence could evolve in Nicotiana by comparing herbivore induced responses among different Nicotiana species under phylogenetic framework, and investigating the trade-offs between defence responses induced by different HAE. Secondly, I will investigate the genetic basis of specificity in HAE induced defence by analysing HAE induced transcriptome changes among different species and functionally validating identified candidate genes use virus induced gene silencing. In addition, the evolutionary pattern of identified candidate genes will be investigated among different Nicotiana species. This project, taking a multiple disciplinary approach, which combines highly advanced metabolic, molecular, and genomic approach in a systematic framework to the topic of herbivore induced plant defence, will be highly novel and relevant for many other plant-herbivore interactions. The investigation on evolutionary pattern of specificity in HAE induced defence could allow the assessment of evolutionary potential of plants to adapt to changing habitats with different herbivore. The identified candidate genes underlie specificity of HAE induced defence could lead a breakthrough in understanding how plant perceive herbivore and have a substantial value for crop protection.
Fire Resistance of Connections in a Composite Floor System (CONFIRE)

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: Türkiye
Call:  (FP7-PEOPLE-2012-IIF, 2012)
Start date: 2013-03-31
End date: 2015-03-30
Duration (months): 24.0
Total project cost (EUR): 166336.2
EU funding (EUR): 166336.2
Participants: 1
Project status: CLOSED

The overall research goal of this proposal is to investigate and improve the structural fire safety in Europe through better prediction and performance of buildings, bridges and other infrastructures in large urban areas by focusing the fundamental behavior of connections in a composite structural frame and by improving the robustness of connections against fire conditions. Europe has one of the worst fire loss records in the industrialized world as demonstrated by the large number of fire-related deaths and the volume of property destruction. The direct financial cost amounted to €15 billion in 2008 in Europe. The cost for providing fire protection to buildings amounted to €12 billion in 2008. Fire represents one of the most severe environmental hazards for the built infrastructure and it is a particularly dangerous event caused by many other hazards such as earthquake, impact and blast. The specific outcomes are the fundamental knowledge on the fire performance of structures, especially the fire resilience and improvements of structural connections, which provide integrity and stability to the global structure. Therefore, the results of this research intend to mitigate the natural hazard risks, which is one of the funded activities in Environment European Research Area and it is stated as one of the priorities of FP7 2012 call for proposals. The Researcher Dr. Selamet has the necessary expertise and technical skills to achieve these objectives by conducting experiments and state-of-the-art numerical (computational) analyses on existing structures such as buildings, bridges, viaducts, and highway overpasses. The results of this research will greatly contribute to the existing structural fire research and will impact the design of new structures for better fire performance in large cities in Europe.

Keywords: structural engineering,connections,composite deck,fire,elevated temperature,fire safety,finite element,g303 civil engineering
Mechanism of Holliday junction dissolution by the Bloom’s Syndrome complex (BLMCOMPLEX)

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: 2013-05-01
End date: 2015-04-30
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 2
Project status: CLOSED

Our genetic material is continually subjected to damage and efficient repair is needed for cancer avoidance. DNA double-strand breaks are cytotoxic and are repaired either by Non Homologous End-Joining or Homologous Recombination (HR). HR provides an important function in DNA repair, where it serves the dual purpose of mending broken chromosomes and recovering sequence information that might be lost at sites of DNA breaks. The recombination process is initiated by exchange of strands between two homologous DNA duplexes (in mitotic cells, recombination generally occurs between two sister chromatids) and the resulting joint molecules can mature into four-way structures known as Holliday junctions. Similar DNA intermediates can be generated during DNA replication via regression of stalled replication forks, which may create a requirement for HJ resolution/dissolution during replication. The primary mechanism of HJ processing involves the BTRR complex which ‘dissolves’ HJs to form non-crossovers, a reaction that is critical to avoid loss of heterozygosity and tumourigenesis. HJs that persist to the late stages of the cell cycle are resolved by the structure-specific endonucleases MUS81-EME1, SLX1-SLX4 or GEN1. Our goal is to address the mechanism of action of the BTRR complex during dHJ dissolution. Understanding this process will further our knowledge of the cancer predisposition disease Bloom’s Syndrome, and will expand our understanding of the relationships between defects in recombinational repair and tumourigenesis. To gain insight into the mechanism of HJ processing by the BTRR complex we will: 1. Determine the molecular mechanism of HJ dissolution using structural and biochemical approaches. 2. Define the interaction surfaces between components of the BTRR complex and how these interactions contribute to the HJ dissolution. 3. Determine the importance of BLM/BTRR dimer formation for in vivo functionality and correlate with mutations found in BS patients.

Keywords: lif / btrr complex / holliday junction dissolution / dna repair / homologous recombination / bloom's syndrome