Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Role of genetic interaction between COMT and Dysbindin in cognitive and schizophrenia-related abnormalities (SCHIZOGENES)

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: 2010-11-01
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

Cognitive deficits are common in most brain disorders and are characteristic of schizophrenia, which is among the most debilitating and costly diseases. Genetic association studies have implicated several potential schizophrenia-susceptibility genes, but a direct genetic cause/mechanism remains elusive. Schizophrenia is dependent upon dysregulation of the dopaminergic system, particularly in the prefrontal cortex (PFC). Catechol-O-methyltransferase (COMT) and dysbindin (dys) are two potential schizophrenia susceptibility genes which regulate cortical dopamine signaling and impact cognitive function. Schizophrenia is likely related to the combined malfunction of multiple genes rather than a single gene mutation. Genetic modifications resulting in selective reduction of either COMT or dys increase dopamine signaling in the PFC. Thus, we predicted that combined COMT*dys reduction in the same individual would demonstrate epistatic interaction between these genes through excessive cortical dopamine signaling. We are accumulating evidence in humans indicating that combined COMT and dys hypomorphisms is strongly associated with schizophrenic phenotypes and cognitive deficits. Therefore, we generated a COMT*dys double null mutant mouse (COMT*dys) which we propose to study for schizophrenia-like phenotypes. Because deficits in executive functions are at the core of schizophrenia, we aim to identify the specific cognitive domains affected by COMT*dys genetic interaction. Additionally, we shall investigate the neurophysiological correlates of such dysregulated behaviors in COMT*dys mice. In a therapeutic prospective, based on the recognized COMT/cannabinoids/schizophrenia interplay, we shall focus on the cross-talk between dopamine- and cannabinoid-mediated signaling in brain regions related to executive functions. This approach will shed light on specific genetic and cellular mechanisms contributing to psychiatric and cognitive abnormalities.

Keywords: neurosciences,psychological sciences,psychiatry,genetically modified organisms,laboratory animal science,genetics,behavioural biology
Generation of Striatal Neurons from Mouse and Human Embryonic Stem Cells: its Relevance for Regenerative Medicine in Huntington's Disease and for Studying Striatal Development. (HESC DIFFERENTIATION)

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: 2010-11-01
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

Huntington’s disease (HD) is an autosomal-dominant, progressive neurodegenerative disorder that usually onsets in midlife. It is characterized by motor, cognitive, and psychiatric symptoms. Once symptomatic, patients are rapidly disabled and require increasing multidisciplinary care. HD is a tremendous burden for medical, social, and family resources. The symptoms and the progression of HD can be linked to its neuropathology, which is characterized by loss of specific neuronal populations in many brain regions. The most important and best studied neuropathology is found in the basal ganglia, in particular a gross atrophy of the striatum. The striatum is characterized by different neuronal populations. Several studies have shown that medium spiny neurons (MSN) are severely affected in HD. MSN are inhibitory projection neurons and are the primary source of striatal projections.Existing medical strategies are available to alleviate some symptoms of HD, including symptomatic therapies (for movements disorders, cognitive impairment, and behavioural manifestations), neuroprotective therapies (anti-glutamatergic drugs), and preventive therapies (for anticipating the clinical onset). Nevertheless, it remains clear that the progressive neurodegenerative process is essentially untreatable medically. For this reason new regenerative therapies that replace neuronal populations and restore function are of great interest and a mandatory research field. This proposal aims at developing new strategies for producing fully functional human striatal neurons from hES with the goal of a future transplantation in HD.

Keywords: applied biology,neurobiology
Experimental Radiotherapy for Malignant Brain Tumours (ERTMABTU)

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: 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 aim of my project is to test two novel experimental radiotherapies which potentially can improve the quality life in patients with malignant brain tumours or with multiple brain metastases. Both methods are being developed at international synchrotron facilities. One of the techniques, microbeam radiation therapy (MRT), is already being studied by several groups and my work is focused on the assessment of adverse effects like memory deficits and bystander effects. Concept and equipment for the second technique, pencilbeam radiotherapy, have only recently been developed at the ESRF in France. Our team will be the first to obtain biological data and assist in developing the technique to a point where a valid assessment can be made regarding its feasibility for therapeutic approach in human patients. All tests will be conducted in well-validated small animal models for an advanced, highly malignant primary brain tumour and for multiple brain metastases from a mamma carcinoma. We will study the acute effects of the radiotherapy in short-term experiments as well as generate survival curves and behavioural data in long-term survivors. In order to document the efficacy of the experimental therapy we will also use a high-resolution synchrotron-based X-ray imaging technique, in which small groups of cells loaded with an X-ray opaque marker can be detected. The applicant for this project is one of the four patent holders for this method. The Marie Curie Reintegration Grant would help me to establish my own work group in Freiburg, thereby combining my previous research experience with the interests of the Department of Stereotactic Neurosurgery and the Laboratory of Molecular Neurosurgery, where I have been working since September 2009. The project also integrates research facilities in three European countries (Germany, France and Italy) as well as a collaboration with a radiobiology team from McMaster University in Hamilton, Canada.

Keywords: medical sciences,anticancer therapy,neuropsychology,experimental physics,medical physics,biomedical engineering
Simulation Modeling to Improve Decision Making in Complex-Dynamic Environments (SIMID)

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: Türkiye
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2010-12-01
End date: 2014-11-30
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The overall aim of this project is to improve decision making in the presence of dynamic complexity, which is a challenging task. The main reason behind this challenge is the inadequacy of our intuitive skills in coping with complex dynamic decision-making situations. Dynamic complexity often overwhelms human decision makers, leading to poor decisions. Effective learning cannot typically take place in complex decision making environments. Simulation game based human experiments show that performances of participants initially improve, but quickly plateau at substantially non-optimum levels after a few trials with the same game. Most interestingly, the dynamic complexity we refer to does not necessitate hundreds or even tens of variables. It has been established that the dynamics of just 2-3 variables can be very complex, if their interactions involve delayed feedback loops and non-linear relations. Managing sustainable growth in public and private domains is a typical example of systemic-dynamic complexity. In early growth phases, growth is relatively easy and the decision makers do not recognize the approaching limits, especially since such limits are not fixed, but dynamically created by the very growth process itself. When the growth limits are recognized, it is often too late to avoid the imminent collapse, due to delays and non-linear effects in the system. The main objective of this project is to explore the roots of such decision complexities on relatively small simulation models and suggest methods and heuristics to improve decision making in complex environments. System dynamics method will be used in building models that will then be converted into interactive games on which decisions of subjects will be tested. A training method will be developed and tested for the subjects and decision heuristics will be developed and tested by mathematical formulations.

Keywords: dynamic decision making,system dynamics,systems modeling,systems simulation,simulation games,dynamic complexity,decision making heuristics,cognitive load
Cognitive and Cooperative Signal Processing Technologies for Remote Sensing Applications (COGSENSE)

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: Türkiye
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-09-01
End date: 2014-08-31
Duration (months): 36.0
Total project cost (EUR): 75000.0
EU funding (EUR): 75000.0
Participants: 1
Project status: CLOSED

Cognitive and cooperative sensing is a novel concept in signal processing that promises to revolutionize the way we interpret and understand our world. It has even been hailed as “a way of the future” in remote sensing networks . Smart or intelligent sensor networks have the potential to impact almost every aspect of our lives through applications such as smart homes, environmental monitoring, security, disaster detection and assessment, noninvasive health monitoring, and traffic information systems. Remote sensing refers to the ability to extract information about the properties or nature of a phenomenon without coming into direct contact. Typically, this is accomplished by exploiting sensors such as cameras, radar systems, thermal devices, sound detectors, seismic, and magnetometers. Cognitive and cooperative sensing envisions not just the fusion of information gathered from multiple sources, but intelligent data gathering geared towards removing the need for human intervention, capable of adaptively controlling and selecting sensors within the network for optimal performance. Our research forms a key stepping stone towards achieving this ultimate goal by pursuing several tasks that can be grouped into two primary categories: 1)Detection, estimation, and tracking algorithms for cognitive, distributed sensor networks, and 2)Multi-sensor intelligent information fusion. This research project holds promise to yield significant advances in a variety of applications, which are defined as main research challenges in the FP7 ICT, Environment and Security Themes of the 2010 Workprogramme, at a time when the application of cognition to remote sensing is still in an embryonic stage. We have played a significant role in initial research relating to this project, and are therefore in a very good position to lead the solution of the problems posed in this project.

Keywords: distributed sensor networks,remote sensing,image processing and signal processing,cognitive sensing
DEVELOPMENT OF AN OPTICAL BACKSCATTER SENSOR FOR DETERMINING THERMAL DENATURATION OF WHEY PROTEINS DURING MILK PROCESSING (DENATUREPROBE)

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: Spain
Call:  (FP7-PEOPLE-2010-RG, 2010)
Start date: 2011-01-01
End date: 2015-05-02
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

The heat denaturation of whey proteins impacts the functional properties of milk. After denaturing, β-lactoglobulin (β-LG) associates with κ-casein (κ-CN), a protein located in the surface of the casein micelle. This association significantly impairs milk coagulation by creating a steric obstacle for κ-CN hydrolysis −a critical phenomenon initiating coagulation− and by increasing the gel moisture retention. Correlations of the degree of β-LG denaturation to gelation time, gel firmness, and gel moisture content have been widely documented. The resulting high moisture and soft gels are undesirable for cheese manufacture but advisable in yogurt processing, as it aids in preventing one of its most frequent defects, wheying-off. Early prediction of the potential gelling strength of milk will allow milk batches to be used for their most suitable purposes. The economical impact this would have on the dairy industry, in addition to the non-existence of a simple method of protein denaturation measurement, motivates this research. The goal of this project is the development of an optical sensor technology for inline determination of β-LG denaturation and subsequent association with κ-CN during milk heat treatment. Given the scattering properties of the micelles, light backscatter was chosen for optical measurement. Preliminary experiments indicate that light backscatter response is proportional to heat treatment intensity, which suggests that light scatter could be used to determine the whey protein denaturation degree. The development of the proposed sensor technology will require: a) finding the adequate wavelength/s, b) developing a robust prediction algorithm, and c) obtaining chemical data supporting the observed optical responses. Successful development of this optic sensor technology will aid in the decision-making process of dairy plants for the efficient use of raw milk and the assurance of a high quality product.

Keywords: dairy science,sensors,process control,food quality,automation
Regeneration and Target Reinnervation after Spinal Cord Injury (AXON REGENERATION)

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: 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

Recent studies have indicated that combinatorial treatments that target multiple mechanisms are necessary to address the limited regenerative capacity in the adult nervous system. We have shown that chemotropic guidance by growth factor gradients, activation of cell-intrinsic regenerative programs and suitable cellular bridges at a lesion site allow for axons to extend across a lesion site in the injured spinal cord. Further, regenerated axons form ultrastructurally identified synapses with appropriate target neurons. However, several challenges that limit the relevance of current approaches remain: Regenerating axons only extend for limited distances beyond the lesion site and axons are not functional possibly due to an insufficient number of synapses or a lack of myelination. The proposed experiments will address these limitations in 3 specific aims. We will examine spatially and temporally controlled expression of neurotrophic factors (NT-3) to enhance the distance of regeneration and target reinnervation by ascending sensory axons after adult spinal cord injury. We will further define the requirements for persistent target innervation using transient neurotrophin expression and we will examine whether localized degradation of inhibitory extracellular matrix will enhance synapse formation with target neurons. Finally, we will determine whether Schwann cell and oligodendrocyte precursor cell grafts can re-myelinate regenerating axons and augment functional connectivity and electrophysiological recovery of regenerated axons.

Keywords: neurosciences,spinal cord injury,axonal regeneration,gene therapy,neurotrophic factors
Low Temperature Magnetic Force Microscopy Study of Topological Insulators (LOWT-MFM-OF-TIS)

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 study of topological insulators (TIs) is a budding field that is enjoying a fervor of activity. Recent discoveries show that new physics can exist in semiconductors with strong spin-orbit coupling. The most exotic class of TIs - "strong topological insulators" (STIs) - is a new state of matter, the hallmark of which is an odd number of topologically protected surface states. We will search for one of the most profound properties of these surfaces states. This predicted, but not yet observed property, is the topological magneto-electric effect (TME), which does not rely on interactions or many-body physics unlike most other emergent effects in solids. In the TME, an applied electric field induces a magnetic field that is proportional to an odd multiple of the fine structure constant. The TME arises when magnetism on the surface of the sample lifts the topological protection of the surface states by locally breaking time reversal symmetry. This gives rise to a special quantum Hall state. The TME is a fingerprint of that state. It is crucial to determine under what conditions the TME occurs, and whether other effects such as electron-electron interactions interfere with it. A low temperature magnetic force microscope (MFM) is an ideal tool for this project since it allows us to induce and measure both electric and magnetic fields at low temperatures. Guided by a suggestion by Qi et al. [Science 323, 1184 (2009)], we will subject the surface states to a magnetic field for breaking their time reversal invariance. This will give rise to the TME. Subsequently we will determine the magnetic field that is induced by electric charge near the surface of the sample by measuring the forces acting on the magnetic MFM tip. We will probe the TME by studying how it is affected by various parameters, such as temperature and applied magnetic field. Beyond establishing a profound property of the surface states, this will open the road to constructing exotic devices based on STIs.

Keywords: experimental physics,electronic,magnetic and superconductive properties,topological insulators,surface probe microscopy,quantum hall effect,spintronics,electrons in low dimensions
Diversion of adherens junctions by bacterial type III effectors during Shigella invasion of polarized intestinal epithelial cells (SHIGELLA INDUCED EMT)

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: France
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

Shigella is a gram-negative enteropathogenic bacterium responsible for dysentery in humans. The type III secretion system (T3SS) encoded on a large plasmid is a key virulence factor of Shigella. Upon epithelial contact, the T3SS allows the translocation of effector proteins into the target cells subverting host cell signal transduction pathways. These T3SS effectors reorganize the actin cytoskeleton through the targeting of RhoGTPases and tyrosine kinase signaling, leading to localized membrane ruffling and subsequent bacterial invasion of host cells. Recent evidence indicate that as opposed to what is observed in non-polarized cells, the coordinated activity of the T3SS effectors, IpgB1 and IpgB2 that activate RhoGTPases, is required for invasion of polarized intestinal epithelial cells that form highly organized intercellular junctions. Adherens junctions (AJs) are regulated by Rho GTPases and tyrosine kinases. In particular, the disruption of AJs linked to epithelial-to-mesenchymal transition (EMT) implicates signaling processes that are reminiscent to those observed during Shigella invasion. These results suggest that the diversion of AJs by these Shigella effectors is necessary for bacterial invasion. In this proposal, we will characterize signaling events mediated by T3SS effectors leading to the transient activation of an EMT-like pathway implicating RhoGTPases and tyrosine kinase signaling, accounting for the breaching of the epithelial barrier by this enteroinvasive bacterial pathogen. This proposal which addresses a key process of bacterial pathogenesis in a relevant epithelial cell system is likely to have profound implications on our understanding of mechanisms underlying the regulation of the epithelial barrier homeostasis and its manipulation by invasive pathogens.

Keywords: health sciences