Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Xylanases as models for understanding enzymatic catalysis (XYLANASES)

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-2011-IOF, 2011)
Start date: 2012-08-20
End date: 2014-08-19
Duration (months): 24.0
Total project cost (EUR): 176368.8
EU funding (EUR): 176368.8
Participants: 1
Project status: CLOSED

Enzymes are essential for catalysis of the biochemical reactions that are characteristic of all living cells. Detailed explorations of these transformations have afforded a wealth of insight into the mechanisms of enzyme catalysis, heralding a range of enzyme applications. In spite of these advancements, further mechanistic studies on the fundamentals of enzymatic catalysis are still essential if we are to fully understand how enzymes effect the considerable 10e17 fold rate enhancements achieved under physiological conditions. A major challenge is to understand how the remote parts of the protein contribute to catalysis, that is; why are enzymes so big and how can mutations distant from the active site influence catalysis? Given that proteins are commonly built from only 20 amino acids, it seems reasonable a priori that during evolution of an enzyme, mutation of residues at remote sites have occurred to optimize the necessarily subtle changes in transition state configurations which must be achieved at the active site. Glycosidases are particularly appropriate model systems for such studies since they are ubiquitous, amenable to kinetic, structural and mutagenic studies and well organised into sequence defined glycoside hydrolase families. The xylanases from Cellulomonas fimi (Cex) and Bacillus circulans (Bcx) have been established as among the best mechanistically and structurally characterised enzymes, making them ideal systems with which to probe the roles played by remote residues in catalysis. In this project the fellow, Dr Martin A. Fascione will adopt a multidisciplinary approach to determine how subtle changes to TS configurations are transmitted from remote sites in enzymes using a combination of molecular biology, mutagenesis, protein semisynthesis, enzyme kinetics, protein NMR, all during the outgoing phase with Professor Stephen G. Withers (UBC), and protein X-ray crystallography during the reintegration phase with Professor Gideon J. Davies FRS (York).

Keywords: enzyme mechanisms,xylanases,carbohydrates,remote mutations,chemical biology,enzimology,molecular biology
High precision reactor neutrino programm at APC (REACTNUTHETA13APC)

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-2011-IEF, 2011)
Start date: 2012-09-01
End date: 2014-08-31
Duration (months): 24.0
Total project cost (EUR): 193594.8
EU funding (EUR): 193594.8
Participants: 1
Project status: CLOSED

This proposal has been designed for Dr Novella to become involved in fundamental neutrino oscillation research with the Double Chooz (DC) experiment, led by Dr de Kerret and Dr Cabrera (at the AstroParticule et Cosmologie laboratory). DC is the most competitive EU-based neutrino oscillations experiment, which leads the world on the measurement of the PMNS mixing matrix parameter theta13. DC should improve the current limit by x7 from the best limit to date set by the CHOOZ experiment. The main challenge for DC is to reduce significantly the systematic errors arising from the flux uncertainties. Thus, two identical detectors are used such that the neutrino oscillation signal extraction is independent from the flux normalisation. DC, in addition, is expected to have a critical impact to pave the technological ground necessary for both the improvement of future reactor experiments and the use of neutrino detector to monitor the evolution of fuels in nuclear reactors. The International Atomic Energy Agency is particularly interested in the latter results as they could help to solve difficult socio-political problems arising when nuclear reactors are used to generate non-authorised substances aiming military ends. This proposal relies on two remarkable matches: i) that between the fellow profile and the training offered by the host through activities in DC and ii) that between the time-scale of the proposed project and the experiment schedule. This proposal embodies an excellent opportunity for the fellow to diversify his research career in the leading research of his interest while reinforcing his professional maturity by granting him with responsibilities in core systems of the experiment. The project will be wrapped up with the neutrino oscillation data analysis leading to publications of expected deep impact to the community boosting the visibility and appeal of the fellow career.

Keywords: particle physics,neutrinos,neutrino oscillations,pmns,reactor neutrinos,theta 13
Mathematical Models and High Performance Computing for Deposition and Absorption in Physiological Flows (MATCOMPHYS)

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-2011-IEF, 2011)
Start date: 2013-05-02
End date: 2015-05-01
Duration (months): 24.0
Total project cost (EUR): 168896.4
EU funding (EUR): 168896.4
Participants: 1
Project status: CLOSED

The project involves the development of mathematical models and their implementation as software code for high performance computing clusters. The physical problem studied involves two related topics: particle deposition and solute absorption in respiratory airways, and tumour metastasis in arterioles and capillaries. The aim is to couple micro-scale phenomena to large 3D incompressible flow simulations. These topics are chosen for their clinical relevance and complex, coupled nature that requires large-scale computing. The numerical tools to be developed are twofold, namely 1D geometric multi-scale networks and Lagrangian mesh-free schemes. The 1D models will serve as fluid boundary conditions of the main conduit, and represent the vascular bed in the tissue. The 1D models are based on Cosserat director theory. A Lagrangian mesh-free scheme will be used to model the multi-component fluids (whole blood and particle-laden air). This approach will easily cope with multi-body interactions and the deformation of the corpuscles; hence it will model the micro-scales and will interface with existing incompressible solver at the host institution. The Lagrangian mesh-free method is based on radial basis function and point interpolation schemes. The facilities at the host institution are among the best in Europe for high performance scientific computing. The supervisor is experienced in computational mechanics, parallel programming, and biomedical applications. These include simulations of large 3D incompressible flow simulations in the respiratory airways and extensive branching arteries, which are both the applications in this project. The proposed project integrates the candidate's field of expertise in numerical analysis and fluid mechanics in physiology, with high performance computing and large-scale integrated problems. Acquiring these skills will enhance, diversify and strengthen the candidate, and further his inter-disciplinary and inter-sectoral research focuses.

Keywords: engineering mathematics,numerical analysis,biomedical engineering,computer engineering,parallel computing,medical physics,oncology,haematology,medicine
Reconstructing the imprint of ecology on the genetic phylogeography of the Plague in Central Asia and China. (PLAGUEECO2GENO)

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: Norway
Call:  (FP7-PEOPLE-2011-IEF, 2011)
Start date: 2012-04-01
End date: 2014-03-31
Duration (months): 24.0
Total project cost (EUR): 208353.6
EU funding (EUR): 208353.6
Participants: 1
Project status: CLOSED

Yersinia pestis, the causative agent of plague, is a flea-borne disease that caused at least three devastating pandemics in the last two millenia[Stenseth08]. Plague is endemic in wildlife rodents, and the ecological and epidemiological dynamics of the rodent-plague system are the underlying cause of outbreaks in human populations. However, our current understanding of this system is insufficient to mitigate the risk. In this project the researcher will uniquely combine the disciplines of theoretical biology, molecular/evolutionary genetics, epidemiology and ecology to address this important issue. The Centre of Ecological and Evolutionary Synthesis (CEES) in Oslo, Norway has access to unique archives on plague outbreaks in rodents and humans in Central Asia and China. These archives, and the available expertise on the genetic phylogeography of the plague at CEES, provide a great opportunity for the applicant researcher to integrate epidemiological and genetic knowledge of plague with his expertise on dynamic modelling of ecosystems. In return, CEES researchers will benefit from being exposed to these simulation models, and their application in analysing complex ecosystems, as well the contact network of the applicant researcher with modelling groups in the Netherlands and Europe. This project would both significantly strengthen plague research, and would have important corollary impacts on public health and risk assessment. The project will use individual-based models of small rodent ecologies through which plague can spread, and observe the changes in the genetic variance of plague. These changes will be abstracted into a Cellular Automata (CA) [Hogeweg10], a modelling formalism that is suitable for simulating large ecological systems. The ecological and epidemiological dynamics of plague within the CA model will be studied in detail and under different hypothesis of plague spread, and compared against the observed genetic variance in plague in Asia.

Keywords: modelling,plague,rodents,evolutionary genetics,ecology,epidemiology
PRODIMA: PRObabilistic Data and information Integration with provenance MAnagement (PRODIMA)

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-2011-IEF, 2011)
Start date: 2013-03-01
End date: 2015-02-28
Duration (months): 24.0
Total project cost (EUR): 200371.8
EU funding (EUR): 200371.8
Participants: 1
Project status: CLOSED

The PRODIMA project investigates provenance-based probabilistic information integration in the semantic web. During the project, a notion of uncertain provenance will be defined for probabilistic information integration frameworks suitable in the semantic web context. Properties of this notion of uncertain provenance will be formally and logically investigated. Furthermore, scalable reasoning algorithms will be developed for collecting, storing and querying provenance information in order to facilitate the computation of probabilities but als in order to enable provenance-based mapping debugging. By this means reasoning, mapping debugging and provenance management shall be combined through scalable algorithms. The properties algorithms will be investigated formally and logically. At the end of the project, a small demo system will be implemented showing the benefits of provenance-based probabilistic information integration in the semantic web context.

Keywords: internet technology,knowledge engineering
Development of Reporter Tools for an Improved Understanding of Pharmacophore–Protein–Interaction (HALOPHORE)

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: Sweden
Call:  (FP7-PEOPLE-2011-IEF, 2011)
Start date: 2012-04-15
End date: 2014-04-14
Duration (months): 24.0
Total project cost (EUR): 174016.8
EU funding (EUR): 174016.8
Participants: 1
Project status: CLOSED

Halogen bonding is an electron density donation-based weak interaction that has so far almost exclusively been investigated in computational and crystallographic studies. It shows high similarities to hydrogen bonding; however, its applicability for molecular recognition processes long remained unappreciated and has not been thoroughly explored. The main goals of this project are (1) to develop halogenated reporter compounds, using these (2) to perform the first ever systematic physicochemical study of halogen bonding in solutions, and (3) to apply the gained knowledge in structural biology through elucidation of the pharmacophore binding site of native proteins. Halogenated, paramagnetic, organometallic reporter compounds will be prepared using solution-phase organic synthesis. They will first be studied on small, well-designed organic model systems providing halogen bond donor and acceptor sites, mimicking those involved in the binding of pharmacophores to proteins and subsequently be used to investigate weak, protein-ligand interactions.The role of the participating halogen atom, the nature of the electron donors (N, O, S; n- and p-donors) and the influence of the environment (i.e. solvent) on the interaction, will be investigated. In this process NMR techniques will utilize paramagnetic effects and permit simultaneous characterization of bond strength and geometry of weak intermolecular complexes. It will be exploited to gain an atomic level understanding of anaesthesia with proteins involved in cellular calcium regulation. This in turn is of direct clinical relevance by providing a long-sought understanding of the disease malignant hyperthermia. In the proposed project I wish to combine my knowledge in chemistry, organometallic and physical chemistry to provide new theoretical insights in molecular recognition processes, to apply these for the understanding of pharmacophore–protein–Interaction and thereby give the basis for advances in drug developent.

Keywords: organic chemistry,organometallic chemistry,structural chemistry,halogen bonding,pharmacophore-protein-interaction
TOwards Personalized medicine: defining the role of the bone marrow microenvironment in multiple myeloma (TOP)

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: Netherlands
Call:  (FP7-PEOPLE-2011-IOF, 2011)
Start date: 2012-09-17
End date: 2015-09-16
Duration (months): 36.0
Total project cost (EUR): 274889.1
EU funding (EUR): 274889.1
Participants: 1
Project status: CLOSED

Multiple myeloma (MM), the second most common hematological malignancies, is characterized by an expansion of malignant plasma cells (PCs) in the bone marrow (BM). Despite the development of novel therapies, MM remains an incurable disease with a 5-7 year survival expectancy. MM is usually proceeded by an asymptomatic premalignant state of clonal PC expansion, i.e. MGUS. Progression of MGUS to MM is a multistep process, which is partially dependent on the acquisition of genetic alterations. However, the fact that MM cells strongly depend on the human BM environment (BME) to survive and expand indicates the crucial role of the BME in the etiology of MM. This project aims to study the BME in MM, in relation to disease progression from MGUS to MM, in order to understand the effect of the BME on the tumor cell, supplying new clues on the necessary factors for MM growth. To this end, I will compare BM stromal cells (BMSCs) from MGUS and MM patients, and those from healthy volunteers, on genomic, molecular, and functional level. Data from these studies will be implemented in a novel human MM model. Since this model is based on BMSCs, it enables to study the role of the BME derived from (1)“healthy” BMSCs, genetically manipulated and (2) MM-derived BMSCs. Both approaches allow analyzing the effect of the BME on MM outgrowth. Moreover, in the second approach the effect of MM-derived BMSCs on the proliferation and survival of MGUS-derived PCs will be analyzed to decipher the role of the BME in disease progression. These experiments will show if the BME can induce the progression of MGUS to MM or that secondary genetic aberrations in MGUS-derived PCs are needed. Taken together, this project will clearly contribute to the understanding of how MM cells use and/or manipulate the BME to survive, progress and expand, but even so important how they develop therapy resistance, information necessary to develop innovative therapeutic strategies and to improve patient’s quality of live

Keywords: health sciences,medical sciences,oncology,haematology,multiple myeloma,bone marrow stromal cells
FLUORESCENT ROTORS FOR IMAGING VISCOSITY IN CELLS (FRIVIC)

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-2011-IEF, 2011)
Start date: 2012-09-03
End date: 2014-09-02
Duration (months): 24.0
Total project cost (EUR): 200371.8
EU funding (EUR): 200371.8
Participants: 1
Project status: CLOSED

This project proposes to design and synthesise a series of novel fluorescent molecular rotors able to measure microviscosity of cellular domains based on the fluorescence lifetime. The fluorescence detection is an efficient and direct way to localise the molecules within cells whereas the measurement of the fluorescence lifetime provides a number of additional assets since the fluorescence decay is typically sensitive to the environment of the fluorophore. In molecular rotors the lifetime can be correlated with viscosity of their immediate environment. Besides, fluorescence lifetime is concentration independent and allows to account for the aggregation phenomenon, and other detrimental quenching processes, the data which is unavailable from the simple intensity measurements. As such, lifetime based detection of molecular rotor fluorescence will provide a quick and accurate measure of the microviscosity in individual cell domains, unavailable from other methods. The new molecular rotors, with incorporated substituents to achieve extensive electronic conjugation, will have advantageous spectroscopic properties, such as high two-photon absorption cross sections and red-shifted absorption and emission wavelengths in the tissue therapeutic window, important both for diagnostic and therapy. These new superior dyes will be used for viscosity imaging in cells, with the emphasis on measuring the viscosity of hydrophobic membranes and on the monitoring of the viscosity changes during Photodynamic Therapy (PDT), a light activated cancer treatment of clinical importance. This project has the ideal overlap of experience and expertise between the applicant and the host group. The results will be both of fundamental importance and practical significance, e.g. for the development of future imaging strategies in biological research. This fellowship will enable the applicant to learn new biology-related skills and as such will prove instrumental for her future academic career.

Keywords: molecular rotor,viscosity,cells,fluorescence,lifetime,biological imaging,photodynamic therapy,cellular membrane,two-photon absorption,near-infrared
Past Interglacial Climates at Key Sites: Sea Surface Temperature and Salinity Reconstructions from the Northern North Atlantic during MIS 5e and MIS 11 (PICKS)

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-2011-IEF, 2011)
Start date: 2013-02-11
End date: 2015-02-10
Duration (months): 24.0
Total project cost (EUR): 255069.4
EU funding (EUR): 255069.4
Participants: 1
Project status: CLOSED

The northern North Atlantic ocean represents a key region in the Quaternary climate system because changes in the intensity of the Atlantic Meridional Overturning Circulation (AMOC) occurring here, finally determine glacial-interglacial global changes. The AMOC intensity is mainly conditioned by a combination of sea surface temperatures and salinities of the warm water inflow (the North Atlantic Current and the Norwegian Current) as well as its geographical pattern. Previous sea surface temperature reconstructions based on foraminiferal abundances and alkenones have revealed strong dissimilarities in temporal and geographical patterns of the northward warm water transfer in the Holocene compared to its two potential analogues MIS 5e and MIS 11c. The aim of this project is to reconstruct sea surface salinities and temperatures in the northern North Atlantic during these two past interglacials using novel methods based on the hydrogen isotopic composition of alkenones and the lipid membrane composition of the marine prokaryote Thaumarchaea, respectively. The main question which we would like to address is if deglaciation effects in the Nordic seas could result in restrictions of the warm water inflow and changes in the configuration of warm water advection in this region. Our results will have implications for the modelling of AMOC functioning and, therefore, on climate prediction.

Keywords: natural sciences,chemical oceanography,salinity reconstructions from dd of alkenones,texl86 temperature reconstructions,northern north atlantic,mis 5e,mis 11