Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Cell-type-specific modulation of protein homeostasis in health and disease (PROTEOSTASIS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Israel
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-09-01
End date: 2014-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The correct folding and assembly of proteins and protein complexes is essential to cellular function. Cells have evolved a network of proteins that detect and correct protein damage to maintain proteome health. However, many protein-misfolding diseases, including Huntington’s and Alzheimer’s diseases, are characterized by the accumulation of damaged proteins with devastating consequences for protein homeostasis (proteostasis), resulting in a collection of deleterious phenotypes and affecting many processes. Given that protein expression is cell-type specific, the proteins affected across different cell types are expected to vary. If this is in fact true, then the protein expression profile of a cell will have a profound impact on the folding capacity of its proteins in health and disease. The objective of this project is to determine how cellular proteostasis is adjusted in a cell-specific manner. To this end, I will combine several complementary approaches to compare proteostasis network interactions in different cell types of Caenorhabditis elegans. I will begin by using fluorescent sensors that enable a real-time assessment of proteostasis in a living organism to identify sensor interaction with the proteostasis network in muscle cells. I will then perform cross-tissue analyses of sensor interactions with the proteostasis networks in neuronal and intestinal cells. Finally, I will examine how the chronic expression of misfolded proteins influences sensor interactions with the proteostasis network. This approach will allow me to examine how protein interactions with the cellular proteostasis machinery are changed in response to an altered cellular environment and to determine how the resources of proteostasis are distributed in health and disease. I believe that the proposed research will have broad implications for elucidating the dynamics and limitations of the cellular proteostasis network in a living organism, with long-term implications for therapeutics.

Keywords: cell biology,molecular genetics,proteostasis,protein folding,misfolding,aggregation
Study of Solar Eruptive Phenomena: Understand their Early Phases and Determine their Arrival Times to Earth (SEP)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Greece
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-01-01
End date: 2014-12-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Our Sun is a violent star. Frequently the solar atmosphere is the set of gigantic eruptions. These can be either confined (flares) or ejective (Coronal Mass Ejections; CMEs). Flares release huge amounts of energy while CMEs launch several billion tons of mass into the interplanetary space. Sometimes large scale coronal waves are observed in association with the above phenomena. Flares and CMEs represent the major drivers of intense Space Weather Phenomena, a number of phenomena in the Earth magnetic environment and upper atmosphere which can impact technological systems on Earth and in Space as well as humans in space. Currently, our understanding of these important solar phenomena is limited by the very nature of our observations which are taken from one viewpoint. This gives only 2D projections of intrinsically 3D objects. Moreover, single viewpoint observations could be always prone to projection effects which could mislead the analysis. The situation changed dramatically with the launch in late 2006 of the STEREO mission which supplies the first ever 3D views of the Sun and of the Heliosphere. STEREO consists of two identical satellites which observe the Sun and the Heliosphere from two distinct vantage points. Using the unique and novel 3D aspect of the STEREO data we will address (1) the genesis of CMEs, (2) the relationships between flares-CMEs-Coronal Waves and (3) more accurate determinations of CME arrival times to Earth. I'm a member of the US-based team of the main STEREO instrument and an expert in the analysis of STEREO imaging data. The proposed research will allow to decide between competing models/theories on CME initiation and determine what is the exact relationships between flares-CMES-Coronal Waves. It will also supply the basis of a space weather tool for predicting accurate CME arrival times to Earth. The proposal will enhance my chances of getting tenure and will help setting up a research center at my host.

Keywords: astrophysics
Studying Gravitational Lensing Magnification with PAU and other Surveys (LENSMAGPAU)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: European Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-05-01
End date: 2014-04-30
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

I plan to study the large-scale magnification of galaxies and quasars due to gravitational lensing, advancing the technique of magnification measurement for the purpose of investigating dark matter and dark energy. In particular, I will work on detecting the lensing mass autocorrelation function by studying galaxy-galaxy correlations in three dimensions, and I will also work to develop quasar magnification analyses using variability as a new and useful technique in studying large scale structure. These projects combine aspects of gravitational lensing, large scale structure, and quasar physics research. In order to facilitate these and other analyses, I plan to take a leading role in the calibration of the Physics of the Accelerating Universe (PAU) survey, a Spanish collaboration set to start taking data in 2012. The survey is designed for the optimal ground-based measurement of three-dimensional galaxy correlations, which will allow for the first measurement of the lensing mass-mass correlation function as well as precise measurements of the galaxy-mass and galaxy-galaxy correlation functions. These results will place valuable constraints on cosmological parameters describing the behavior of dark matter and dark energy.

Keywords: cosmology,astrophysics
Exploiting innate immune evasion strategies of Staphylococcus aureus for the design of novel antibody-based therapeutic agents for the treatment of bacteremia (COMPSTAPH)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Greece
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-10-15
End date: 2014-10-14
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Staphylococcus aureus is a widely disseminated human pathogen whose virulence is associated with a broad range of severe and potentially fatal health complications. It has been shown to produce a series of immunomodulators that promote virulence by affecting both arms of the host immune response. Complement (C’) represents a key innate immune effector that protects against infection, and S. aureus has evolved several strategies to evade C’ neutralization. C’ proteins are essential for the propagation of host inflammatory reactions to bacterial infection and serve as attractive targets for the dampening of this response by pathogens. Indeed, several S. aureus-secreted proteins have been described to have C’ inhibitory activity. To this date, no systematic research effort has been placed on the development of complement-based antimicrobial therapeutics that might exploit immune evasion mechanisms of S. aureus. The current proposal focuses on dissecting critical interactions of S. aureus immune evasion molecules with key components of the innate immune response (complement and cytokine networks) by means of antibody-targeted studies on virulence and inflammation. Our research aims to: 1. Characterize antibodies from S. aureus-exposed individuals that recognize key microbial evasion targets and can attenuate inflammation in a whole blood model of S. aureus-induced bacteremia. Studies will also focus on dissecting the neutralizing capacity of these antibodies on a broad spectrum of inflammatory mediators triggered by bacterial infection. 2. Develop single-chain antibodies against S. aureus proteins identified in Aim 1 as being targets for pathogen neutralization by phage library approaches. The therapeutic efficacy of these library-generated antibodies will be evaluated in in vitro models of inflammation and in vivo mouse models of sepsis. These studies are anticipated to provide a framework for the design of novel antibody-based therapeutics for infectious diseases

Keywords: infectious diseases,innate immunity,staphylococcus,complement evasion,antibodies
The role of Rac1 and Rac3 in cortical interneuron development (RACS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: European Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Greece
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-10-01
End date: 2013-09-30
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

GABAergic interneurons play important roles in cortical function and provide the main source of inhibition to cortical microcircuits. Impaired interneuron function results in severe neurodevelopmental disorders such as schizophrenia, epilepsy and autism. Although recent studies have uncovered some of the molecular mechanisms underlying interneuron development, the intracellular components involved are still unknown. Our proposed work, aims to elucidate the role of specific signalling cascades during birth, migration and specification of interneurons, and thus shed light on the intracellular machinery that regulates their proper development. Rac proteins integrate multiple extracellular signals and are required for many processes in diverse cell types, including cytoskeleton organization, vesicle trafficking, transcription, cell cycle progression, and apoptosis. We are interested in elucidating the roles of Rac1 and Rac3 specifically in MGE-derived interneurons, a population that comprises the majority of cortical interneurons. We have used conditional Rac1 deficient mice (specifically in the MGE) combined with Rac3 null mice and we found that 50% of MGE derived GABAergic interneurons fail to migrate and populate the cortex. MGE-derived interneurons missing both Rac proteins show an even more severe defect (80%). The aim of this proposal is to elucidate the mechanism of Rac1 and 3 action in interneuron development by assaying for: a) the polarity and the involvement of actin/microtubule dynamics in Rac deficient interneurons, b) the nature of the defect in interneuron progenitors as it concerns cell cycle behaviour c) the individual role of each of the two Rac proteins and the involvement of downstream effectors of the Rac pathway and d) the functional properties of interneurons. The experiments designed combine molecular genetics, imaging, cellular and biochemical assays to reveal the mechanism of action of these intracellular mediators of interneuron development

Keywords: gabaergic interneurons,rho-gtpases,rac1,rac3,cdc42,cell cycle,development,migration,wave,limk,mdia,actin remodeling,cyclin d1,cdk 4,cdk6
Network analysis of bacterial multi-cellular patterning (BACTERIAL PATTERNS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Israel
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-10-01
End date: 2014-09-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Defining the mechanisms by which cells cooperate to form complex structures and a common function is a fundamental problem in both developmental biology and socio-biology. Cooperative interactions among bacteria are a relatively simple, yet medically important, model system where this problem can be explored in its full generality. Specifically, bacterial growth on surfaces is often accompanied by formation of complex patterns and increased resilience to diverse external insults. The importance of multiple co-existing cellular differentiated states and of specific cell signaling processes, to spatial patterning and development of bacterial communities has been demonstrated in several systems, including the well-characterized microbe, Bacillus subtilis. However, the nature of these interactions and the way they control the spatial organization of differentiation and patterning is unclear. Specifically, we do not understand (1) when and where are genes and cell fates expressed? (2) What is the spatial organization of cell fates? (3) How does the interaction between fates give rise to spatial order? Here, we suggest addressing these questions by utilizing a novel light-activated gene expression system. This will be used to control the spatial and temporal gene expression profile of a library of patterning-related genes. Time-lapse fluorescence microscopy will be used to monitor the dynamic expression of relevant reporters in wild-type and spatially perturbed backgrounds. We will use mathematical modeling to integrate the results into a predictive model of pattern formation and community development. My previous experience in mathematical modeling of spatial systems, and experimental background in developmental genetics, microbiology and advanced microscopy provides a well suited background to successfully pursue this important problem.

Keywords: microbiology,systems bioloy,optogenetics,microscopy,bacterial developmet,biofilm,pattern formtion,signaling network,mathematical modeling,image analysis,morhogen
Cosmological Applications of Lensing and Intrinsic Correlations of Ellipticities (CALICE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: European Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Portugal
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-09-01
End date: 2013-08-31
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

Cosmology has recently entered a concordance and precision era with its predictions being accurately and successfully tested by a number of observational probes. This status however is achieved at the expense of 96% of the Universe being assumed to be in still unknown forms known as Dark Matter and Dark Energy. CALICE addresses open questions of Cosmology using Gravitational Lensing. This technique describes how light is deflected as it passes through the gravitational field generated by matter. Its effect can be detected in the distorted images of galaxies via a modification of their shapes. This “cosmic shear” effect is a unique probe of the geometry and matter distribution in the Universe. It has however its systematic effects which must be controlled to be efficiently used in future high precision surveys, such as the satellite Euclid mission. Given the current and potential possibilities of cosmic shear, CALICE is divided in two parts. On one hand it will use data from CFHTLS and COSMOS surveys in three key goals. The first is to look for possible deviations of gravity effects from the ones predicted by General Relativity and study their evolution using tomographic measurements. The second is to study Dark Energy by combining lensing with measurements of the variation of the fine-structure constant and the proton-to-electron mass ratio. The third goal is to use the information on the evolution of matter distribution and its properties at large scales, to constrain the neutrinos mass. On the other hand CALICE will contribute to the preparation of future surveys by conducting a study, using numerical simulations, of astrophysical effects that produce correlations in galaxies shapes, which contaminate the measurements. CALICE will produce detail modelling of various correlations as function of galaxy type, satellite distribution, magnitude and distance, creating a template to be used as a reference for removing such contaminations from future data.

Keywords: physical sciences,observational cosmology,gravitational lensing,dark energy,modified gravity
Developing Innovative Capabilities in Teams (TEAM INNOVATION)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Israel
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-10-01
End date: 2015-09-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 2
Project status: CLOSED

To maintain and enhance their effectiveness within rapidly changing environment, organizations need to continuously develop creative products processes and services and implement them within budget and quality constraints. To achieve this goal, organizations increasingly rely on teams, consisting of members with different knowledge, skills and perspectives. Paradoxically, the processes leading to idea creation and implementation may contradict each other. Idea creation requires flexibility, out-of-the-box thinking, exploration, risk taking and tolerance of mistakes. Idea implementation, in contrast, happens within organizational constraints and includes promoting the idea through the acceptable channels, prototyping, testing, and assuring that the products, processes or services are reliable and meet customers’ requirements. The first objective of the proposed project is to examine whether teams can improve their innovation capabilities by learning how to reconcile the contradictory requirements, inherent in the innovation process. The second objective is to distinguish between different types of organizational constraints (i.e., structural vs. process constraints) and test their effect on team innovation. The third objective is to compare three managerial approaches for managing strategic contradictions (i.e., ambidexterity, sequential and hybrid) and test their effect on team innovation. The suggested project will be conducted in a laboratory setting using a product development simulation. In Phase 1, three-member teams will be asked to develop a creative product while adhering to cost and/or quality constraints. In Phase 2, three-member teams will be trained to manage contradictory requirements using one of three managerial approaches, and then will perform the product development task. The primary dependant variables will be creativity and adherence to constraints. In addition, possible mediating team processes will be examined.

Keywords: psychological sciences,social sciences,behavioural sciences,teams,innovation,creativity
Understanding and manipulating Antibody Dependent Cell Cytotoxicity (ADCC) by human Natural Killer (NK) cells (ADCC)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: European Re-integration Grants
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-09-01
End date: 2013-02-28
Duration (months): 30.0
Total project cost (EUR): 37500.0
EU funding (EUR): 37500.0
Participants: 1
Project status: CLOSED

High-resolution microscope images of immune cells contacting other cells have revealed temporary membrane structures, often called immune synapses (IS). Proteins commonly segregate into specific regions at the contacts between cells, and exploring how such changing arrangements of proteins occur and how they control immune cell communication is the new science opened up by the immune synapse concept. Over the last decade the use of monoclonal antibodies has revolutionised the treatment of severe human diseases, such as non hodgkins lymphoma (NHL) and rheumatoid arthritis (RA). One way that these antibodies work is by triggering Natural Killer cells to directly kill diseased target cells. Typically antibodies have been used to either block ligand receptor interactions or to evoke antibody effector function and kill malignant target cells by antibody-dependent cell cytotoxicity (ADCC). Crucially, nobody has yet determined what happens at IS when antibodies trigger killing of diseased cells. Through this project we will focus our research to improve our basic understanding of the molecular dynamics that occur during ADCC and to investigate antibodies specifically engineered to enhance ADCC. Here, we plan to use state-of-the-art technologies to image IS during antibody-mediated killing with a view to learning how to best optimize antibodies for this function. Specifically, the spatial relationship and segregation of proteins at the submicrometer scale will be determined during ADCC and compared for the different antibodies and model systems developed. This will establish what determines the efficiency of ADCC and will facilitate the rational design of modified antibodies for optimal medical use. This project will benefit from the knowledge and experience in imaging and cell biology techniques gained by the researcher during her initial training. It will also provide the researcher with invaluable new experience adding to her career development.

Keywords: natural sciences,natural killer cells,antibody dependent cell cytotoxicity,monoclonal antibodies,immune synapse,imaging,antibody engineering