Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Targeting the BMP4/pSMAD/CDX-2 axis for Eradicating Barrett’s esophagus (TARGETS4BARRETT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Netherlands
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-04-01
End date: 2017-03-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

One of the consequences of the high Socio-economical standards is the increase of diseases related to abdominal obesity, such as gastro-esophageal reflux disease. Barrett’s esophagus is a mucosal adaptation to chronic reflux disease, which is associated with an increased risk of developing esophageal adenocarcinoma. This cancer has become a significant health burden. One effective strategy to control further increase of this highly malignant cancer would be by population wide eradication of Barrett’s esophagus. Hereto, it will be necessary to target the key biological mechanisms that are involved in the process of Barrett’s metaplasia. By means of my recent discovery that Barrett’s esophagus develops through a collaboration of two factors: the caudal homeobox gene CDX-2 and the BMP4/pSMAD pathway, this strategy has become within reach! The objectives are to generate molecular inhibitors and a strategic Barrett model in order to develop and test a molecular cure for Barrett’s esophagus. The key question that will be addressed is: Will inhibition of the BMP4/pSMAD/CDX-2 axis abrogate the homeostasis of intestinal metaplasia and lead to the resolution of Barrett’s esophagus? To answer this question, I propose to synthesize highly specific single domain-antibodies to inhibit the BMP4/pSMAD/CDX-2 axis. With my recent novel insights, I will develop a strategic transgenic Barrett mouse model. I will use a smart drug delivery formula for safe application of these inhibitors in vivo. Finally, the strategic Barrett model will be used to evaluate the novel inhibitors for their efficacy for reversing Barrett’s esophagus back into squamous epithelium. I expect that by the end of the study the stage will be set for future evaluation of these inhibitors in clinical trials for their efficacy to cure Barrett’s esophagus patients. This may lead to population wide control of Barrett’s esophagus, eventually resulting in prevention of further increase of the esophageal adenocarcinoma.

Keywords: barrett esophagus,bmp,llama antibodies,metaplasia,esophageal adenocarcinoma,mouse model.
The development of the hippocampal spatial representation system (DEVSPACE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Neurosciences and neural disorders
Countries involved: United Kingdom
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2017-12-31
Duration (months): 72.0
Total project cost (EUR): 1491930.0
EU funding (EUR): 1491930.0
Participants: 1
Project status: CLOSED

This proposal will address how a multimodal cognitive system, the neural representation of space in the hippocampus, emerges during development. There is a long tradition in neuroscience of studying the development of primary sensory systems, but fewer studies have concentrated on the development of brain networks supporting higher-order cognitive representations. Our recent findings (Wills, Cacucci et al. Science, 2010) provide a starting point to fill this gap, charting the emergence of spatial responses of hippocampal formation neurons, using in vivo recording in awake, behaving rats. The hippocampal formation supports neural representations of the environment ('cognitive maps') by means of which an animal can locate itself and navigate to a goal location. It contains three classes of spatially-tuned cells: place cells, which code for location, head direction cells, which code for directional orientation and grid cells, which may code for distance travelled. The key aim of this proposal is to delineate the developmental processes that create this neural representation of space, focusing on the representations of place and direction. We will delineate which sensory information is capable of driving spatial firing, and whether early hippocampal coding is truly spatial in the sense of representing configurations of stimuli and not single cues. How are abstract spatial constructs (place and head direction) built from raw sensory information during development? We will test whether boundary sensitive neurons and angular velocity tuned neurons are the elemental 'building blocks' making up place and directional signals, as suggested by many theoretical models. We will also investigate the role of experience in the construction of spatial representations. Do the network architectures underlying spatial firing emerge through experience-dependent learning mechanisms, or are they the result of self-organizing processes which take place independently of experience?

Keywords: hippocampus,place cells,head direction cells,development,spatial cognition
Getting Research Into Policy in Public Health : transforming the evidence-to-policy response through utilisation of political insights (GRIP-HEALTH)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: United Kingdom,Spain
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1496403.0
EU funding (EUR): 1496403.0
Participants: 2
Project status: CLOSED

There has been increasing frustration in the field of public health with the lack of uptake of research evidence, and continued difficulties in getting evidence of effective health interventions into policy and practice. Calls have often been made to ‘bridge the gap’ between researchers and policy makers, yet little work has been done to analyse the political factors influencing research-to-policy process in public health, and the ways national governments may respond to these challenges. We airm to take the next step in improving the use of evidence in health policy by integrating political data and analysis into efforts to build the government institutions and responses which take up research evidence. Specifically we will apply political science theories and methods from the sub-fields of policy analysis, and public administration to achieve this end. These disciplines have not yet been applied to the challenge of getting evidence into policy in health. A programme of work drawing on these fields can take the next step in the evidence-based health policy movement. The work will map out the multiple political challenges to evidence use, while providing recommendations on how to build government structures supportive of evidence informed policy in particular policy contexts. We will review existing literature, construct a conceptual framework linking political insights with national responses, conduct empirical case studies across a range of countries, and develop a tool to improve government responses to the use of evidence in public health. Finally this programme will work to create a center of excellence on the study of evidence and policy in health.

Keywords: evidence based policy,getting evidence into policy,research-policy relationship,governance of health.
Comparative studies of inbreeding effects on evolutionary processes in non-model animal populations (ECOGENOMICINBREEDING)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: Denmark
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2017-09-30
Duration (months): 69.0
Total project cost (EUR): 1497248.0
EU funding (EUR): 1497248.0
Participants: 1
Project status: CLOSED

Comparative studies of inbreeding and evolution in non-model animal populations: a research proposal directed towards integrating ecological and evolutionary research on inbreeding. Specifically, my aim is to apply novel ecogenomics tools in the study of evolutionary consequences of inbreeding in non-model animal populations. At present, our understanding of inbreeding is dominated by studies of a small number of model organisms. I will undertake comparative studies on inbreeding effects in a genus of spiders containing independently evolved naturally inbreeding species as well as outcrossing sister species. The study of a naturally inbreeding animal species will provide unique insights to consequences of inbreeding for population genetic structure, genome-wide genetic diversity, and evolution of life history traits. Social spiders are not only unique because they naturally inbreed, but also by being cooperative and showing allomaternal brood care including self-sacrifice, and they evolve highly female-biased sex-ratios, a trait that is not well understood in diploid species. My research objectives are 1) to establish a robust phylogeny for comparative studies; 2) to quantify the effects of inbreeding on the genetic diversity within and between populations; 3) to estimate gene flow among inbred lineages to determine whether inbred lineages diversify but retain the potential for gene exchange, or undergo cryptic speciation; 4) to determine effects of inbreeding on gene expression; 5) to investigate the mechanism underlying the genetic sex determination system that cause female biased sex-ratios; and finally 6) to determine whether sex-ratio is under adaptive parental control in response to genetic relatedness and ecological constraints. Addressing these objectives will generate novel insights and expand current knowledge on the evolutionary ecology of inbreeding in wild animal populations.

Keywords: molecular evolution of inbreeding genomes. molecular age and timing of speciation events of inbreeding lineages. x-linked genes for genetic sex determination and evolution of female biased sexratio.
Printed microfluidic counting chambers for low-cost point-of-care diagnostics (INSTANTCOUNT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Netherlands
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-09-01
End date: 2017-04-30
Duration (months): 68.0
Total project cost (EUR): 1496400.0
EU funding (EUR): 1496400.0
Participants: 1
Project status: CLOSED

The goal of "InstantCount" is to develop low-cost point-of-care blood tests based on microfluidic counting chambers and image cytometry (InstantCount tests) for use in challenging environments, e.g. remote areas in developing countries. Preliminary work on CD4 counting (measuring the concentration of helper T-cells in blood in order to diagnose the progression of an HIV infection) demonstrates the feasibility of the concept. I have assembled a prototype instrument for large area fluorescence imaging, developed the image analysis software and microfluidic counting chambers containing dried reagents. The fabrication of these chambers is simple and the used materials cheap, making affordable diagnostics even in the poorest regions appear feasible. However, a clinical evaluation of the tests outside the laboratory environment in rural areas requires improved reproducibility in the fabrication of the chambers, which would also enable the development of new assays, once the properties of the reagent layers can be tailored according to the requirements of different tests. I propose the development of printing techniques for the fabrication of InstantCount tests. Counting chambers with precisely defined thickness will be realised by printing of microbeads embedded in glue. Printing of different types of hydrogel will offer solutions like self-sealing chambers or timed release of reagents with a wide range of molecular sizes without the need for mixing other than by diffusion. With these techniques, we will realise rapid low-cost point-of-care diagnostics for primary health care in remote areas and small medical practices. Complete blood counts for general health screening, CD4 counting and the detection of parasites in red blood cells such as in malaria will be provided. The project will neither require expensive fabrication methods in clean room facilities nor high-resolution optics in the instruments. Printing can bridge the gap between prototyping and production.

Keywords: point-of-care diagnostics,microfluidics,printing techniques,diagnostic tools
Symbiotic bacteria as a delivery system for Nanobodies that target the insect-parasite interplay (NANOSYM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Belgium
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1444370.4
EU funding (EUR): 1444370.4
Participants: 1
Project status: CLOSED

The tsetse fly (Glossina spp.) salivary gland is the final micro-environment where the Trypanosoma brucei parasites adhere and undergo a complex re-programming cycle resulting in an end stage that is re-programmed to continue its life cycle in a new mammalian host. The molecular parasite-vector communications that orchestrate this trypanosome development in tsetse fly salivary glands remain unknown mainly due to the limited availability of experimental tools for functional research. We hypothesize that an innovative paratransgenic approach using the Sodalis glossinidius endosymbiont to deliver Nanobodies that target the trypanosome-tsetse fly crosstalk will open a new avenue to unravel the molecular determinants of this specific parasite-vector association. In this project I will develop an innovative Sodalis-based internal delivery system for Nanobodies to target the tsetse fly – trypanosome interplay and, as final outcome, will generate a trypanosome-resistant tsetse fly. In addition, I will explore the completely ‘unknown’ of the molecular nature of trypanosome adherence to the salivary gland epithelium. This will be addressed by a challenging proteomic-based approach on the tsetse salivary gland - trypanosome membrane complex and by the newly developed paratransgenic approach using the S. glossinidius endosymbiont as an internal delivery system for salivary gland epithelium-targeting Nanobodies. The application of this innovative concept of using pathogen-targeting Nanobodies delivered by insect symbiotic bacteria could be extended to other vector-pathogen systems such as Anopheles gambiae – Plasmodium falciparum and Aedes aegypti – dengue virus.

Keywords: nanobodies,paratransgenesis,vector-parasite interaction,glossina,trypanosoma brucei
Xenophagy and bacterial avoidance (XABA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1599999.6
EU funding (EUR): 1599999.6
Participants: 1
Project status: CLOSED

Autophagy is an essential process that enables cells to engulf and digest portions of their cytoplasm, thereby accomplishing quality and quantity control of organelles, proteins and pathogens. These homeostatic and adaptive function intricately link autophagy to diverse health and disease states including innate immunity. Microbial pathogens that successfully parasitize eukaryotic cells have evolved to evade autophagic microbial defenses (xenophagy) and subvert the host autophagic responses for their own survival and/or growth. Central to xenophagy is cargo recognition and dynamic rearrangements of membrane-bound compartments to sequester and deliver pathogen load for lysosomal degradation. Microbial adaptation strategies identified to date have targeted both of these crucial and intertwining functions. However, the precise molecular mechanisms underpinning pathogen avoidance of host-cell autophagy and immune responses are only poorly understood. This raised specific questions about host-pathogen interactions: (1) What is the dynamic response of the core autophagy system to bacterial pathogens? (2) How does the autophagy pathway impinge on the endocytic system and how do pathogens subvert intracellular vesicle trafficking systems? (3) What is the molecular machinery involved in detecting cargo and how do pathogens counter this response? This proposal seeks to elucidate pathways and functions involved in xenophagy and to identify mechanisms by which pathogens usurpate the anti-bacterial cell-autonomous defence system. To address these questions, we will employ a highly complementary multidisciplinary platform, which combines biochemical, cell and infection biological approaches with emerging proteomics and high-content imaging techniques. Together, this proposal has the potential to uncover novel molecular mechanisms that define the signaling machinery driving xenophagy of pathogens, thereby contributing to advancements in the fields of cell and infection biology.

Keywords: autophagy,rab gtpase cycle,ubiquitylation,image-based rnai,aqua ms,bacterial pathogens
SPHERE: Susceptibility to Particle Health Effects, miRNAs and Exosomes (SPHERE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Italy
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-12-01
End date: 2016-11-30
Duration (months): 60.0
Total project cost (EUR): 1444742.0
EU funding (EUR): 1444742.0
Participants: 1
Project status: CLOSED

In spite of more than two decades of mechanistic research, the recent statement of air pollution and Cardiovascular Diseases (CVD) from the American Heart Association remarked that at front of high degree of consistency of the epidemiology findings showing increased air pollution related CVD risk, the evidence on intermediate mechanisms remains moderate or weak. Exosomes might be the ideal candidate to mediate the effects of air pollution, since potentially they could be produced by the respiratory system, reach the systemic circulation and lead to the development of endothelial dysfunction. The main object of our proposal is to determine whether exposure to air particles and PM-associated metals can modify exosomes (as quantity, size, membrane molecules, procoagulant activity and miRNAs content) in plasma of human subjects and to investigate whether these alterations may be linked to CVD risk factors and outcomes. The study population will include 2000 overweighed/obese subjects presenting at the Center for Obesity and Weight Control, Milan. Obese subjects have been shown to be particularly susceptible to the effects of air pollution. Exposure to air pollutants will be assessed using: a) ambient concentrations of particulate and gaseous air pollutants; b) geographical information and modelling; c) road density and traffic intensity data; d) Metals determination in urine and hair; e) Personal passive samplers (to measure PM), on a subgroup of subjects (n=200). To identify altered exosome-associated miRNAs , we will follow a two-stage, split sample study design: a discovery stage involving OpenArray miRNA expression profiling (on 1000 subjects) and a replication stage involving a real time analysis of the top 10 miRNAs. We will integrate the human study with an in-vitro model using a system made of paired cell cultures (A549 lung/ granulocytes and endothelial cells) to clarify if exosomes produced by lung/granulocytes can directly interact with endothelial cells.

Keywords: microvesicles,microrna,particulate matter exposure
HIgh Speed PRoteomics Analysis (Prot-HiSPRA): Solving the bottlenecks of proteomics technologies for time sensitive proteome driven medical decisions (PROT-HISPRA)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Austria,Hungary,Slovenia,United Kingdom,Russian Federation,Austria
Call:  (FP7-HEALTH-2011-single-stage, 2011)
Start date: 2011-10-01
End date: 2015-03-31
Duration (months): 42.0
Total project cost (EUR): 3212398.88
EU funding (EUR): 2536246.99
Participants: 7
Project status: CLOSED

The main objective of the proposed collaborative project Prot-HiSPRA is to remove time-consuming bottlenecks of existing proteomics technologies (sample preparation, fractionation, proteolysis, separation, data collection, and data mining) and bring the proteome driven analysis into time sensitive clinical practice. Prot-HiSPRA is an objective-driven research project and it aims at generating new knowledge and new technologies which will improve the European competitiveness in the field of applied proteomics. Prot-HiSPRA is planned for the duration of 36 months which is necessary in order to ensure a high-quality validation of the developed high-throughput methodologies. A strong participation of SMEs (partner 2 – MAYLAB, partner 3 – CELS - left the onsortium, partner 6 – RTDs, partner 7 - BIA) will ensure strong innovation and exploitation during HiSPRA. Research activities in the Prot-HiSPRA program can be divided into a technological core project that is tailored to significantly improve on technologies in the fields of proteomics, bioinformatics, and integrated biology. Analytical methods developed with the Prot-HiSPRA project will be exemplified by applying for analysis of clinical samples originating from in vitro fertilization (IVF) procedures. During the IVF process, especially at the moment when decisions are made which embryo can be implanted, decisions must be made so that the process has the greatest chance for success. To further elevate pregnancy rates for IVF a non-invasive, rapid, and robust methods for judging the embryos status is urgently needed to examine the embryos´ proteome. These methods could not only be applied in the described field of reproductive medicine but also in any the other fields of clinical analysis where fast and reliable diagnosis on a proteomic basis could be made available.

Keywords: online sample preparation,nano hplc,intelligent data correlation