Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Fetal adrenal and gonadal sex hormone synthesis in health and disease (FSHS)

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: Germany
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-09-01
End date: 2016-03-10
Duration (months): 36.0
Total project cost (EUR): 45000.0
EU funding (EUR): 45000.0
Participants: 1
Project status: CLOSED

The differentiation of the male and female genital phenotype is established at 7-12 weeks post conception. During this period, maintaining the appropriate intrauterine hormone environment is essential. However, it is surprising how little is known about the intrauterine hormonal milieu and the consequences of hormonal alterations. During her Marie Curie Intra-European Fellowship Dr Reisch’s work provided conclusive evidence for the existence of a novel androgen pathway in the fetal adrenal and its significance for the pathophysiology of oxidoreductase deficiency (ORD), a recently described form of congenital adrenal hyperplasia (CAH). The virilisation observed in CAH due to 21-hydroxylase deficiency (21-OHD), the most common form of CAH affecting 1:10,000 newborns, intricately ties the function of the fetal adrenal cortex to sexual differentiation of the external genitalia. To date, this has been explained by excessive production of adrenal androgens via the classic pathway to androgen synthesis during fetal and postnatal life. However, during fetal life, it is highly likely that the novel alternative pathway also plays a significant role in the pathogenesis of 21-OHD. The research of this grant application will investigate the impact of the newly discovered alternative pathway to fetal androgen biosynthesis on virilisation in 21-OHD via the analysis of the steroid metabolome in urines of pregnant mothers carrying babies affected with 21-OHD and affected newborns. Secondly, the project will elucidate the impact of the fetal adrenal-gonadal hormonal cross-talk on the development of testicular and ovarian adrenal rest tumors in 21-OHD in a model of 21-OHD deficient mice. These tumors are the most common cause of infertility in 21-OHD and current data suggest that they are primed during fetal development. This project has the potential of transfer of the results into patient care, e.g. with regard to refinement of prenatal treatment of CAH patients in the future.

Keywords: health sciences,medicine,endocrinology,gonadal and adrenal development,fetal hormones,congenital adrenal hyperplasia
Studies in Symplectic Geometry and Hamiltonian Dynamics (SSGHD)

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

I propose to pursue several independent studies in symplectic geometry and Hamiltonian dynamics. My research objectives are twofold. First, to solve some of the open research questions described in the proposal, which I consider to be pivotal in the field. Some of these questions have already been studied intensively, and progress toward solving them would be of considerable significance. Second, the proposed research is closely tied to other fields such as convex geometry and asymptotic geometric analysis (Problem 1.1 and 1.2), algebraic geometry and mirror symmetry (Problem 1.4), and the theory of mathematical billiards (Problem 1.3). These connections have already proved fruitful in tackling questions that were out of reach for common symplectic methodology thus far, and I expect further significant results to be within reach. Moreover, partly due to these ties, this research has a wide range of possible applications outside of symplectic geometry. Therefore, my second research objective is to utilize the suggested questions in order to deepen and broaden the connections between symplectic geometry and the above mentioned fields.

Keywords: symplectic geometry,hamiltonian dynamics,quantum homology,lagrangian intersection,geometry of the group of hamiltonian diffeomorphisms,the theory of symplectic capacities
NEUROGENESIS IN 22Q11.2 DELETION SYNDROME: ROLE OF microRNAs (MIRNAS/22Q11DS)

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: Italy
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-06-01
End date: 2015-05-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The 22q11.2 deletion syndrome (22qDS) is the most common hemizygous microdeletion syndrome occurring in humans. Individuals with 22qDS show also a variety of neuro−anatomical defects. Our central hypothesis is that altered miRNAs biogenesis (caused by the hemizygous deletion of Dgcr8, one of the genes located in the 22q11.2 critical region, and required for miRNAs maturation) might impair embryonal/postnatal brain development, thus causing some of the defects observed in brains of 22qDS patients. Our working hypothesis is now further supported by the recent finding that aberrant embryonal neurogenesis is occurring in 22qDS mice and possibly in human patients. However a direct link between altered miRNAs biogenesis and aberrant neurogenesis in 22qDS is still missing. Interestingly, our preliminary results (obtained with hemizygous deletion of Dicer, a gene unrelated to 22qDS, but acting downstream Dgcr8 in the miRNAs maturation pathway) confirm and further expand the observation that reduction in miRNAs dosage affects preferentially the proliferation (or survival) of a basal neural progenitor cells in mice. Thus strengthening the hypothesis of an involvement of miRNAs in the 22qDS. In the current research proposal we aim to investigate whether altered maturation of miRNAs in brains of 22qDS mice, is affecting neurogenesis, and overall, the contribution of altered neurogenesis to the neuro−anatomical/pathological defects observed in 22qDS mice. We then plan to use induced pluripotent stem cells (iPS) from freshly collected fibroblasts of 22qDS patients, and reprogrammed toward neuronal progenitors lineages, in order to verify whether altered miRNAs biogenesis is contributing to some alterations also in a human cellular model of 22qDS. These achievements will allow the straightforward investigation of the cellular defects causing the disease, providing an optimal setting for future systematic drug screenings.

Keywords: health sciences,digeorge syndrome,neurobiology,brain development,neurogenesis,microrna
Gas Phase Structural Dynamics Imaging (GPSDI)

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: 2010-10-01
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

Chemical reaction mechanisms are at the core of fundamental science questions (like the functionality of biological molecules), as well as important technological advances (like the development of new materials). Understanding reaction mechanisms with atomic detail promotes both basic understanding of natural phenomena and knowledge-based technological applications. Despite the giant steps in the last decades in understanding chemical reactivity and achieving more control over chemical reactions at the atomic level, current knowledge comes mainly from spectroscopic and dynamics techniques which probe only a small fraction of the potential energy surface. We propose a different approach: to use Ultrafast Electron Diffraction (UED) to study chemical, physical and biological phenomena by imaging the structure of the intermediates involved as a function of time, all the way from reactants to products. In UED, a short laser pulse triggers the dynamics and diffraction of a short burst of electrons probes the transient structures at ultrashort intervals at the atomic/molecular level. The novelty of the technique has been demonstrated in gas phase as well as surface and materials science problems but there is a lot of room for improvement. If successful, we will construct a novel, state of the art UED instrument and use it to : (1) Probe the structural change during relaxation of photoexcited DNA, seeking to identify the contribution of spectroscopically dark channels, detectable only with UED, and (2) Image transient structures in reaction dynamics problems involving cluster chemistry and conical intersections

Keywords: reaction mechanisms and dynamics,photochemistry,ultrafast electron diffraction,structural dynamics
Smart Magnetic Solutions for Minimally Invasive Surgery (SMART MAG SOLUTIONS)

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: Ireland
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-11-01
End date: 2014-10-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The objective of this proposal is the reintegration of Dr. Pádraig Cantillon-Murphy, a research fellow at Harvard Medical School and MIT (Boston, USA), back to Europe, as Assistant Lecturer at Cork Institute of Technology (CIT). His reintegration will result in (i) research independence and increased European collaboration and funding support for Dr. Cantillon-Murphy, (ii) novel and high-impact research at CIT and (iii) sustained collaborations between Irish and EU engineers, physicians and surgeons. Dr. Cantillon-Murphy's principal research focus at CIT focus will be the development of smart magnetic solutions for minimally invasive surgery. Recent innovations in surgery, such as Natural Orifice Transluminal Endoscopic Surgery (NOTES), have the potential to result in scarless surgery, less anesthesia, shorter hospitalisation times, and lower healthcare costs for European citizens. Unlike traditional laparoscopy, which uses 3 or more transcutaneous ports of access, in NOTES, there is no transcutaneous port. Instead, an endoscope is passed though a natural orifice (e.g., mouth) to gain access to the peritoneal cavity via a “transluminal” incision through the stomach. However, one of the fundamental problems facing NOTES to create a secure, leak-free access port to target organs through the gastric wall. Dr. Cantillon-Murphy has developed a safe, simple and cost-effective solution using magnetic self-assembly to overcome this challenge. As faculty at Cork Institute of Technology (CIT) and in conjunction with the Medical Engineering Design and Innovation Centre (MEDIC) at CIT, Dr. Cantillon-Murphy will continue to pursue ground-breaking engineering solutions to NOTES and other applications of smart magnetic solutions in surgical procedures such as hernia repair, colorectal cancer and obesity intervention.

Keywords: medical physics,biomedical engineering,surgery,medical instrumentation
Functional redundancy of marine bacteria in biogeochemical cycles (FUNDIVERSITY)

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: 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

Microorganisms drive the biogeochemical cycles on Earth. Traditionally, biogeochemical studies have relied on the analysis of microorganisms isolated from the environment, but they only represent a minor percentage of the existing diversity (<1%). New approaches such as metagenomics or functional genomics have revolutionized our ability to link microbial ecology to biogeochemical processes, expanding our knowledge about the genes involved in key biogechemical processes, the microorganisms imediating them, and the distribution and redundancy of functions in the environment. A central but seldom addressed question is whether different bacterial taxa are unique or redundant in their functions in the environment. This has important implications for the modeling of biogeochemical cycles. The objective of this project is to identify functional groups of bacteria and analyse their levels of redundancy in a marine long-term ecological station which has been monthly sampled for physical, chemical, and biological variables since 2001. We will incorporate molecular analyses during 3 years and make use of cutting-edge tools such as metagenomics and pyrosequencing to analyze the structure of functional bacterial groups. We will test whether the diversity of functional groups of bacteria change at a seasonal scale, whether these changes are related to environmental or biological parameters, and in turn, whether they affect the biogeochemical cycling. As a result, we expect to verify whether some ecosystem processes are a common metabolic strategy among different bacterial phylotypes and identify key bacterial populations involved in biogeochemical cycling in this coastal marine site. Identifying functional groups of microbes and their ecological characteristics will allow recognizing “microbial boxes” of different biogeochemical significance, improve the predictions of the models, and, overall, transform our understanding of globally important biogeochemical processes.

Keywords: aquatic ecology,coastal ecosystems,marine biodiversity,bacteriology,environmental biology,functional biology
The role of surface scattering and impurities in metallic lateral Spin-valve Devices (LSV-SIE)

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 field of spintronics is receiving continuous and growing attention, due to the expected increase in functions of lateral spintronics devices to include promising elements such as nonvolatile spin field effect transistors, ultra-fast memories and spin-based quantum computers. But, in order to utilize such lateral applications in industrial settings, a critical improvement in their performance is necessary, for which much basic research is still required. An important issue, which is relevant to the nano-scale lateral devices and has not received much attention, is surface effects. Here, spin scattering from the surface can lead to loss of all spin signals. The study and understanding of spin scattering, due to surface effects is one of the major goals of the proposed research. The study of lateral spintronics devices has led to discovery of many new phenomena; include spin transfer torque; crossed Andreev reflections and the spin Hall Effect. In the latter, anisotropic spin dependent scattering in non-magnetic materials induce a transverse spin current. This enables the generation of spin polarized currents in non-magnetic material without the need of injection from a ferromagnet. But, a larger magnitude of the effect is vital if one considers this a realistic source of spin-polarized current for application. We aim at increasing the spin Hall effect in metallic spintronics devices by resolving quantitatively the geometrical and material related contributions of the effect. Study of these spin transport phenomena via local probe measurements is a very powerful approach, as has been demonstrated for semiconductors using optical methods. We intend to develop and measure the local spin accumulation by an MFM-based measurement with an anticipated ~10 nm spatial resolution. This is x100 better than previous measurements, and will enable us to spatially resolve the local spin accumulation in metallic devices.

Keywords: solid state physics,electron-based nano-devices,experimental physics,spintronics,spin diffusion,scanning probe microscopy
Structural and functional insight into the biosynthesis of endogenous lipidic messengers by the N-Acyl Phosphatidylethanolamine Phospholipase D (NAPE-PLD) (NAPE-PLD)

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: Italy
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-10-01
End date: 2013-09-30
Duration (months): 36.0
Total project cost (EUR): 75000.0
EU funding (EUR): 75000.0
Participants: 1
Project status: CLOSED

Imbalances of human major lipid signaling pathways contribute to progression in inflammation, neurodegenerative and metabolic diseases. Among lipidic messengers, the family of bioactive N-Acylethanolamines (NAEs) is agonist at cannabinoid and nuclear α-type peroxisome proliferator-activated receptors. The ability of NAEs and their metabolic enzymes to modulate neurotransmission and a variety of pathophysiological processes, including inflammation, appetite, pain and mood, provides unique chances for drug discovery. Upon stimulation, bioactive NAEs are generated from cell membranes in a two-step pathway, which involves an N-acyltransferase and an N-acylphosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD). NAEs bearing saturated and monounsaturated long acyl chains are significantly decreased in NAPE-PLD(-/-) mice suggesting this enzymes as key regulators of the NAE-mediated signaling potential. Very little is known about the molecular architecture of NAPE-PLD and the specific functional role of its N- and C-terminal domains. If given a chance, I will study domain trafficking in activated cells and to solve the X-ray structure of this membrane-bound protein. I will characterize the thermodynamics and kinetics of enzyme interactions, which are essential in understanding how NAPE-PLD synthesizes NEAs and controls their cellular level. Findings will be used for a rational approach in the design of potent and selective NAPE-PLD ligands, which can be exploited pharmacologically to modulate the level of NAEs in inflammation, pain, and neurodegenerative disorders. These aims are a common goal of cell biology, structural biology, pharmacology, and medicinal chemistry, which could give an invaluable blueprint for the design of selective inhibitors, thus strongly impacting both EU scientific research and EU molecular medicine. The Drug Discovery and Development Unit of the Italian Institute of Technology is a unique working environment for their achievement.

Keywords: lipid signaling,n-acyl ethanolamines,phospholipase d,metallo-beta-lactamase,inflammation,neurodegeneration,membrane protein,interaction,kinetics,x-ray crystallography,structure-based inhibitor design
Regulation of Inflammation by Macrophages in Chronic Granulomatous Diseases (RIMINCGD)

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: Germany
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-03-01
End date: 2014-02-28
Duration (months): 36.0
Total project cost (EUR): 75000.0
EU funding (EUR): 75000.0
Participants: 1
Project status: CLOSED

Chronic granulomatous disease (CGD) affects children and young adults and is associated with significant morbidity, mortality and socio-economic costs. CGD is caused by the genetic deficiency of NADPH oxidase (Nox). The characteristic lesion in CGD is the development of granulomas, or confined areas of tissue inflammation, which are characterized by the presence of macrophages (Mph) and Mph-derived multinucleated giant cells. Granulomas physiologically function to wall off microorganisms or foreign bodies. In CGD, however, granulomas persist in the absence of detectable microorganisms, thus causing severe life-threatening complications. We hypothesize that Nox deficiency results in hyperinflammation due to a Mph-intrinsic defect. The goals of this study are 1. to determine the role of ‘inflammatory’ monocytes in granuloma formation in the Nox2-/- CGD mouse model using a loss-of-function and adoptive transfer approach and 2. to analyze mechanisms by which Nox deficiency suppresses ‘anti-inflammatory’ macrophage functions that physiologically control hyperinflammation and mediate tissue repair, using genetic and molecular biology approaches. The second goal will be accomplished in collaboration with Dr. Lionel Ivashkiv (New York). Eventually, these studies aim at the identification of new Mph-specific treatment modalities for CGD. Funding of this proposal will allow the applicant to develop an independent area of research in the hosting Centre for Chronic Immunodeficiency (CCI) in Freiburg, Germany and will thus give her the chance to establish herself as an independent investigator in Europe. The hosting CCI will benefit from the applicant’s scientific and technical expertise in macrophage activation in inflammatory diseases. Integrating the applicant into the CCI will further serve as a starting point of a long lasting collaboration with the internationally renowned group on macrophage signaling and inflammation headed by Dr Lionel Ivahskiv.

Keywords: innate immunity,immune disorders,primary immunodeficiency,inflammation,granuloma,macrophages,monocytes,alternative macrophages,chronic granulomatous disease,tlr2,bacterial lipoproteins