Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Understanding how immunostimulant combinations in adjuvants synergise to enhance vaccine responses (ADJSYN)

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: Belgium
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2013-07-01
End date: 2015-06-30
Duration (months): 24.0
Total project cost (EUR): 169800.0
EU funding (EUR): 169800.0
Participants: 1
Project status: CLOSED

The need to develop vaccines against challenging diseases such as malaria or tuberculosis requires effective adjuvants to improve the immune responses against purified antigens, as these antigens often lack intrinsic immunogenicity. Most adjuvants act on innate immunity leading to the activation of antigen presenting cells and induction of memory T cell and antibody responses to the vaccine. Including more than one immunostimulant within an adjuvant has the capacity to improve the quality of the immune response to a vaccine. In this respect, combinatorial adjuvants may emulate aspects of the natural immune response to a pathogen, which involves multiple innate pathways typically triggered by stimuli from pathogen-derived molecules. GSK Vaccines has pioneered the use of immunostimulants in adjuvant formulations for human vaccines. One of its propriety Adjuvant Systems, AS01, is a liposome-based and contains the immunostimulants MPL and QS-21. In pre-clinical models, antigen-specific cellular immune responses are synergistically enhanced with the combination of MPL and QS-21. Hence the overall scientific objective of the ADJSYN project is to understand the basis of the MPL and QS-21 synergy by focussing on key molecular and cellular mediators of the synergistic response, and on how these mediators interact. This project will use a multidisciplinary approach, involving bioinformatics, immunology, imaging and molecular biology, and will be conducted through several collaborations within Europe. Therefore ADJSYN should deliver mechanistic insights on how to engage innate immune pathways to promote effective adaptive immune responses; and the methodology should be transferable for the analysis of adjuvants formulated with other immunostimulants. Moreover, because AS01 is being evaluated in an increasing number of vaccines, the insights from this project could have direct relevance for translational research and the rationale design of new human vaccines.

Keywords: l611 prevention and treatment of infection by pathogens,l601 innate immunity,l210 bioinformatics,l604 immunosignalling,l307 cell signalling and cellular interactions
On-the-fly nonadiabatic quantum dynamics suitable for large biomolecules: Developing the DD-vMCG method (DQDPROT)

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: 2013-07-01
End date: 2015-06-30
Duration (months): 24.0
Total project cost (EUR): 231283.2
EU funding (EUR): 231283.2
Participants: 1
Project status: CLOSED

Nonadiabatic effects play an important role in many molecular systems, including those of biological relevance. Processes such as photosynthesis, photoreception and bioluminescence are initiated by photoexcitation followed by the evolution of the system with splitting of the nuclear wavepacket in the manifold of electronic states. Nonadiabatic quantum dynamics is a method of choice to study these processes theoretically as the Born-Oppenheimer approximation fails in the regions where electronic and nuclear motions are coupled. The usual approach involves a preliminary calculation of the potential energy surface of the system, which becomes unfeasible with the increase of dimensionality. In order to treat many-atomic systems a direct dynamics variational multi-configuration Gaussian wavepacket (DD-vMCG) method has been developed. It enables on-the-fly potential energy evaluation due to the usage of localized Gaussian functions as a basis set while retaining the full quantum character of the nuclear wavepacket. The method still has a field for improvement, especially with respect to the algorithm of diabatisation as only an approximate version of this is currently implemented. In the current project we therefore aim at upgrading the DD-vMCG method and further applying it to biological systems in which nonadiabatic effects play a role (e.g. the green fluorescent protein). In order to study big systems we plan to use a hybrid quantum mechanical/molecular mechanical approach that allows us to treat the most important part of the system at the quantum mechanical level, while the remainder is treated with less accurate, but much faster classical mechanical methods. We thus will open the doors for the accurate quantum dynamical investigations of biological systems, that were only previously studied using significant approximations.

Keywords: quantum chemistry,direct quantum dynamics,potential energy surfaces,nonadiabatic phenomena,excited states,gaussian wavepackets,bioluminescence,photodynamics,diabatisation
REGULATION OF CHOLESTEROL HOMEOSTASIS BY THE ARH-MEDIATED ENDOCYTOSIS OF THE LDL RECEPTOR (CHOLESTRUCTURE)

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: Israel
Call:  (FP7-PEOPLE-2012-IIF, 2012)
Start date: 2013-06-01
End date: 2015-05-31
Duration (months): 24.0
Total project cost (EUR): 227231.2
EU funding (EUR): 227231.2
Participants: 1
Project status: CLOSED

Hypercholesterolemia, high levels of plasma LDL-cholesterol, is a major risk factor for atherosclerosis and premature coronary heart disease (CHD), a leading cause of death in worldwide. The clearance of LDL from the circulation occurs via endocytosis with the LDL-receptor (LDLR) mainly by liver cells. This hepatic recruitment of the LDL-LDLR complex to the clathrin-coated pits is dependent on the endocytic adaptor protein, autosomal recessive hypercholesterolemia (ARH), which recognizes the NPxY internalization signal on the LDLR cytoplasmic tail. Consequently, naturally occurring mutations in either LDLR or in ARH lead to sever hypercholesterolemia and premature onset of CHD. Therefore, studying the molecular interactions ARH forms at the cell surface to facilitate endocytosis of the LDLR is central to our understanding of cholesterol homeostasis. I recently solved a novel crystal structure of the LDLR-ARH interface at atomic resolution. Surprisingly, the structure reveals that the phosphotyrosine-binding (PTB) domain of ARH recognizes a longer portion of the LDLR tail than previously believed, and that ARH has discrete structural determinants for somewhat promiscuous binding of NPxY containing signals of various flanking specificities. To gain a detailed mechanistic understanding for the unique endoctytic function of ARH, this proposal will investigate (1) The molecular basis for receptor recognition by solving crystal structures of ARH with all the receptor tails it is known to bind; (2) The interaction of ARH with phosphoinositides and with cell membrane via tools from cell biology and biochemistry; (3) The interaction of ARH with clathrin and its major endocytic adaptor AP-2 structurally and biochemically. This multidisciplinary approach will significantly extend the molecular knowledge on sorting of LDLR to clathrin-coated pits which is highly significant for cellular physiology and for homeostasis of plasma cholesterol and cardiovascular health.

Keywords: lipoprotein,ldl,cholesterol,dyslipidemia,hypercholesterolemia,arh,ldl receptor,endocytosis,atherosclerosis,coronary heart disease
Circuit mechanisms of fear vs. reward in the limbic system (FEARREWARDCIRCUITS)

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: Austria
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2014-03-01
End date: 2016-02-29
Duration (months): 24.0
Total project cost (EUR): 179137.2
EU funding (EUR): 179137.2
Participants: 1
Project status: CLOSED

Emotions are a central part of our mental self and health, playing a crucial role in guiding behaviors essential for survival. For instance, threats evoke fear and avoidance behaviors; conversely, rewards induce reward-states and approach behaviors. Resolving how the variety of emotions emerges in the brain remains a major challenge for modern neuroscience. The main objective of the proposed research is to investigate how opposite emotions like fear and reward are differentially processed in the limbic system. We hypothesize that these basic emotional states are encoded by interactions of neural circuits specific for negative or positive emotional valence and circuits for arousal. To address this problem, we will first aim to develop a novel genetic tagging approach for differential brain-wide screening for emotional valence and arousal circuits in a combined Pavlovian fear and reward conditioning task. Second, we will investigate how fear and reward are encoded in selected hotspots within this circuitry: by pharmaco- and optogenetic manipulations, we will test whether emotional states require the activity of, and can be induced by, a combination of valence and arousal circuits. This research will provide a circuit mechanistic framework for understanding the neural organization of emotions in health and disease and establishes a novel imaging method which will be useful for investigating other brain functions in a similar fashion. This postdoctoral project will significantly contribute to my career development by complementing my expertise in behavioral neuroscience with training in circuit neuroscience and by reinforcing my professional maturity and leadership qualities. Moreover, the reciprocal transfer of my expertise in behavioral neuroscience to the host laboratory and, in turn, my training in cutting-edge technologies in preparation for a position in my home country, is a tremendous opportunity for the diffusion of knowledge within the European Research Area.

Keywords: neuroscience,emotion,pavlovian conditioning,neural circuit,amygdala,mesolimbic system,optogenetic,pharmacogenetic,mice
Identification of novel correlates of protection to accelerate the introduction of vaccines against typhoid into populations with high disease burden. (MCF_IIF BLOHMKE 2012)

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: 2013-10-01
End date: 2015-09-30
Duration (months): 24.0
Total project cost (EUR): 221606.4
EU funding (EUR): 221606.4
Participants: 1
Project status: CLOSED

Salmonella enterica serovar Typhi (S. Typhi) is a major human pathogen causing approximately 22 million new infections and 600,000 deaths annually posing a significant challenge for strategies to control the infection in endemic areas. Current vaccines are of limited efficacy and cannot be used in young children. Development of new alternatives has stalled due to the high costs associated with performing large field trials as no reliable correlates of protection exist. Using a novel human challenge model recently established by the Oxford Vaccine Group, this research aims to identify easy-to-measure gene expression signatures predictive of vaccine-conferred protection (correlates of protection). Microarray technology will be used to determine the longitudinal gene expression levels in whole blood from individuals vaccinated against typhoid and subsequently challenged with S. Typhi. In order to identify the molecular events underlying the host-response to vaccination and infection with S. Typhi, transcriptional patterns will be identified using computational approaches such as network analysis and pathway and gene ontology over-representation analysis. Furthermore, gene expression signatures correlating with clinical and immunobiological data will indicate the mechanisms governing vaccine-derived protection. These data will facilitate the identification of reliable correlates of protection to accelerate the development and deployment of novel typhoid vaccines.

Keywords: typhoid fever,infectious diseases,systems vaccinology,innate immunity
Public Debt and the Republic: Florentine Political Thought and Public Finance from 1470 to 1537. (CREDIT AND REPUBLIC)

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: 2013-06-01
End date: 2015-05-31
Duration (months): 24.0
Total project cost (EUR): 309235.2
EU funding (EUR): 309235.2
Participants: 1
Project status: CLOSED

The need to develop tools for the understanding of public finance has been highlighted by the financial crisis that broke in 2008. The research ambition of this project on the origins of political economy is to show that the intellectual history of public finance can generate such tools. Its main objective is to produce a monograph entitled *Public Debt and the Republic: Florentine Political Thought and Public Finance from 1470 to 1537*, which takes financial thought back to its roots, at a moment when the development of democratic institutions came to contradict the development of public credit. As such it also illuminates an understudied aspect of the political thought of the ‘Machiavellian Moment’, which redirected the tradition of classical Republicanism, thus defining one of the cornerstones of European modernity. This objective is achieved through: • exploitation of the Florentine archives. These preserve unique and unexplored materials which render feasible the in-depth reconstruction of the foundation of modern financial thought and practice • collaboration with the host institute. The Centre for the Study of the History of Political Thought (Queen Mary, University of London) hosts one of the largest concentrations of specialists in this field. The proposed investigation contributes to a central interdisciplinary research project of the Centre, on ‘Popular Sovereignty’. Undertaking the proposed project at the host institute allows the applicant to: • resume his European academic career after a five-semester hiatus researching and teaching in the USA and South Africa • further his career options in order to attain an academic position at a leading European institute • enhance his interdisciplinary skills, intertwining the history of ideas and the study of systems of administration • optimize his theoretical reflection, adept at both transnational and transhistorical analysis • acquire systematic knowledge of the financial culture of early modern Florence.

Keywords: s409 history of ideas - intellectual history,debt,public - europe - history,florence (italy) - politics and government (1470-1540),s410 social - economic - cultural and political history
The potential of investments in energy efficiency and distributed generation to contribute to local development in Italy. Which role for local communities? (LOCALENERGY)

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: Italy
Call:  (FP7-PEOPLE-2012-IEF, 2012)
Start date: 2014-02-01
End date: 2016-07-02
Duration (months): 24.0
Total project cost (EUR): 179739.6
EU funding (EUR): 179739.6
Participants: 1
Project status: CLOSED

This is a proposal for an interdisciplinary investigation into the potential of investments in energy efficiency and renewable generation to contribute to local development in Italy, with a focus on Italian ‘convergence objective’ regions (i.e. Calabria, Puglia, Sicilia and Campania). The project will consider several types of emerging business models for the implementation of energy measures at local level, their conditions for successful implementation and the relative role and implications for local actors and communities. It will analyse the case of implementing these emerging business models in the specific context of the territories targeted, exploring their appropriateness to respond to wider local communities development objectives and to maximise returns for the communities themselves. As such, the project will pay particular attention at emerging and innovative forms of implementation of community projects. An assessment of the target territory energy demand and generation potential (the energy map) coupled with engagement with the local stakeholders (i.e. local authorities and other public bodies, local communities as well as potential investors and technology suppliers in the private sector) will provide location specific data and information necessary to understand the socio-economic and energy context as well as specific local energy needs. Such information and the relationship developed with the main local stakeholders will be used for the identification of two to three case studies for which a detailed feasibility assessment of the investment in energy efficiency and renewable generation under different business models will be done, with the view of identifying best practice, barriers to implementation and assess replicability potential.

Keywords: energy economics,energy policy,renewables,distributed energy,e106 natural resources and environmental economics,e113 urban and regional economics,e112 social economics
Multi-wavelength study of accretion onto black holes and its evolution during cosmic times (HIGH-Z & MULTI-Λ)

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: 2013-03-01
End date: 2015-02-28
Duration (months): 24.0
Total project cost (EUR): 161968.8
EU funding (EUR): 161968.8
Participants: 1
Project status: CLOSED

The beginning of this century can be considered a golden age for X-ray astronomy, with the launch of XMM-Newton, Chandra and Suzaku, three cornerstones of the ESA, NASA and JAXA space programs. These observatories, although more than 10yr old, still deliver excellent science and X-ray astronomy now leads many fields of astronomical investigation. However, only small-medium class X-ray missions are planned to be launched in the next 10-15yr, thus shrinking the space for new discoveries in X-rays alone. The two years at MPE will allow to diversify my scientific expertise by: i) expanding my research field into: a) Optical-Infra Red (IR) bands; b) evolution of Active Galactic Nuclei (AGN) variability through cosmic time; ii) being granted access to Optical-IR facilities and new X-ray missions. The proposed project will allow to: 1) measure the evolution of AGN variability over cosmic time using large AGN samples, thus also assessing whether AGN can be used as standard candles; 2) measure SgrA*'s duty cycle, its past activity, the Molecular Cloud (MC) Galactic Center (GC) distribution, the level of GC cosmic rays, the irradiation induced MC chemistry; 3) if SgrA* will go into outburst (a gas cloud will reach SgrA* in mid 2013) we will lead the X-ray investigation of this major event (e.g. the switching on of an AGN, jet-disc creation) that will remain in astronomy records; 4) link (thanks to NuSTAR, the new NASA X-ray mission) the variability properties of the Compton reflection hump, the FeK line and the soft excess in AGN, to finally understand the origin of these components; 5) monitoring the evolution of the cross-correlation function and the spectral energy distribution, during an entire Galactic Black Hole (GBH) outburst, to echo-map and determine the transformation of the disc-jet-corona system geometry; 6) understand if GBH winds can keep the alpha-disc stable, constrain the connections between wind-jet-state in GBH and the connections between GBH and AGN winds.

Keywords: p301 astronomy - astrophysics and cosmology,p104 nuclear astrophysics,p111 relativity
Quantum Optical Control (QOCO)

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: France
Call:  (FP7-PEOPLE-2012-IIF, 2012)
Start date: 2013-03-01
End date: 2015-02-28
Duration (months): 24.0
Total project cost (EUR): 194046.6
EU funding (EUR): 194046.6
Participants: 1
Project status: CLOSED

This proposal details the planned incorporation of femtsecond pulse shaping and coherent control strategies into the repertoire of continuous variable quantum optics with the explicit goals of both manipulating and analyzing nonclassical, multimode structures. Since multimode entanglement is a prerequisite for numerous applications in quantum metrology and quantum information science, femtosecond optical frequency combs, which are inherently multimode, are a promising candidate for the development of such states. Toward this end, optical parametric oscillators have proven effective for the creation of multimode quantum frequency combs, and the further introduction of pulse shaping strategies will follow a two-pronged approach. First, shaped pulses will serve as an interrogative probe that enables complete characterization of the nonclassical properties of individual modes comprising the total state. Subsequently, the shaping of the femtosecond pulses that drive the parametric interaction will allow active manipulation of the multimode entanglement. The on-demand customization of nonclassical multimode states is expected to be an essential resource in the continued development of continuous variable quantum optics.

Keywords: p108 optics and quantum optics,p109 lasers and laser physics,p116 metrology and measurement,femtosecond,pulse shaping,multimode,continuous variable