Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Insulin resistance and diabetic nephropathy - development of novel in vivo models for drug discovery (DIADRUG)

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: Finland
Call:  (ERC-2009-StG, 2009)
Start date: 2009-11-01
End date: 2014-10-31
Duration (months): 60.0
Total project cost (EUR): 2000000.0
EU funding (EUR): 2000000.0
Participants: 1
Project status: CLOSED

Up to one third of diabetic patients develop nephropathy, a serious complication of diabetes. Microalbuminuria is the earliest sign of the complication, which may ultimately develop to end-stage renal disease requiring dialysis or a kidney transplant. Insulin resistance and metabolic syndrome are associated with an increased risk for diabetic nephropathy. Interestingly, glomerular epithelial cells or podocytes have recently been shown to be insulin responsive. Further, nephrin, a key structural component of podocytes, is essential for insulin action in these cells. Our novel findings show that adaptor protein CD2AP, an interaction partner of nephrin, associates with regulators of insulin signaling and glucose transport in glomeruli. The results suggest that nephrin and CD2AP are involved, by association with these proteins, in the regulation of insulin signaling and glucose transport in podocytes. We hypothesize that podocytes can develop insulin resistance and that disturbances in insulin response affect podocyte function and contribute to the development of diabetic nephropathy. The aim of this project is to clarify the mechanisms leading to development of insulin resistance in podocytes and to study the association between insulin resistance and the development of diabetic nephropathy. For this we will develop transgenic zebrafish and mouse models by overexpressing/knocking down insulin signaling-associated proteins specifically in podocytes. Further, we aim to identify novel drug leads to treat insulin resistance and diabetic nephropathy by performing high-throughput small molecule library screens on the developed transgenic fish models. The ultimate goal is to find a treatment to combat the early stages of diabetic nephropathy in humans.

Keywords: transgenic fish,transgenic mice,drug lead discovery,kidney,podocyte,diabetic nephropathy,insulin signaling,insulin resistance
Source and efficacy of human olfactory ensheathing cells in the repair of brachial plexus avulsion. (HORAB)

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: United Kingdom
Call:  (ERC-2009-StG, 2009)
Start date: 2010-01-01
End date: 2014-12-31
Duration (months): 60.0
Total project cost (EUR): 1600000.0
EU funding (EUR): 1600000.0
Participants: 1
Project status: CLOSED

Olfactory ensheathing cells (OECs) are a unique group of cells which were originally discovered in the olfactory bulb, the part of the brain that receives the sense of smell. These cells have now been found in the nose, and have the potential to encourage damaged nerve fibres to regenerate. When these cells are transplanted into the damaged spinal cords of rats they facilitate repair of the nerve fibres, and this results in an improved ability to climb and breath. It is now possible to obtain these cells from the noses of patients with brachial plexus avulsion (a longitudinal spinal cord injury) and to purify and multiply them for transplantation back into the same patient s damaged brachial plexus, to possibly cure injuries which were previously untreatable. However it is first necessary to find a safe and reliable way to obtain these cells from patients, develop a protocol for cleanroom manufacturing these cells under UK Good Manufacturing Practice (GMP) guidelines, and check whether human cells have the same reparative effects in the laboratory and animal studies, compared to what we already know about rat cells. The research programme consists of the following projects: 1. To develop a protocol for obtaining these cells in optimum quantities, by taking samples from volunteer patients who are undergoing nasal endoscopy for other reasons, and develop an effective culture method to maximise the yield of OECs. 2. To culture these cells under GMP conditions, using standardised reagents, and develop a protocol that ensures the maximum yield in a new culture facility. 3. To transplant autologous OECs into the site of injury in patients with complete brachial plexus avulsion, and assess the safety and efficacy of the technique. This will also allow us to obtain pilot data to allow planning of a future randomised controlled trial of OEC transplantation. 4. To study the effects of OECs derived from rat mucosa in animal models of brachial plexus avulsion

Keywords: transplantation,brachial plexus,trauma
Physical Forces Driving Collective Cell Migration: from Genes to Mechanism (GENESFORCEMOTION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: ERC Starting Grant Interdisciplinary Panel
Countries involved: Spain
Call:  (ERC-2009-StG, 2009)
Start date: 2010-01-01
End date: 2014-12-31
Duration (months): 60.0
Total project cost (EUR): 1749745.0
EU funding (EUR): 1749745.0
Participants: 2
Project status: CLOSED

Fundamental biological processes including morphogenesis, tissue repair, and tumour metastasis require collective cell motions, and to drive these motions cells exert traction forces on their surroundings. The mechanisms underlying this basic principle of health and disease have been debated intensively and, using a variety of methods in vivo, in vitro, and in silico, much conflicting evidence has accumulated. This conflicting evidence has been in every case indirect or inferential, however, because within the moving cell group the physical forces themselves have remained inaccessible to direct experimental observation. To fill this gap, this ERC application describes an interdisciplinary project to uncover the physical mechanisms underlying collective cell migration. In Objective 1, I propose to develop technology to map forces that cells within moving groups exert on each other and on their extracellular matrix. In Objective 2, we will use siRNA technology to provide a systematic analysis of the genes that regulate force generation and transmission in a migrating epithelial cell sheet. In Objective 3, we will use this pool of data to establish a constitutive link between genes, forces and collective cell motion. Although these Objectives present major technical and scientific challenges, the feasibility of each is supported by a unique technical know-how and by a productive track record in the field of cell biophysics.

Keywords: cell migration,cell mechanics,biomechanics
Social Vaccination in Ant Colonies: from Individual Mechanisms to Society Effects (SOCIALVACCINES)

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: Austria,Germany
Call:  (ERC-2009-StG, 2009)
Start date: 2010-04-01
End date: 2015-03-31
Duration (months): 60.0
Total project cost (EUR): 1299780.0
EU funding (EUR): 1299780.0
Participants: 2
Project status: CLOSED

Living in social groups leads to a high risk of disease spread. Insect societies counteracted this threat by evolving sophisticated collective anti-parasite defences, combining the immune systems of all group members and their collective social hygienic behaviours. I recently described a direct link between these social and individual defences, by showing that social contact to an infected individual results in a protective Social Vaccination in its nestmate ants: the latter survived an infection with the same pathogen significantly better than control ants that had lived with other healthy ants only. Aim of this project is to elucidate the molecular and physiological mechanisms of this Social Vaccination in individual ants, and its effect on the organisation of collective defences and disease dynamics at the colony level. Preliminary results have shown different protein upregulation in healthy, infected and vaccinated ants, and a detailed analysis of gene and protein expression patterns will define those proteins and their function in anti-parasite defence (postdoc). Observations of the social interactions between infected ants and their group members, and measures of the physiological immune responses of the individuals at different stages of the infection and after the vaccination will further reveal when and how Social Vaccination occurs, how long it endures, and how specific and plastic it is (PhD 1). At the colony level, the social role of vaccinated individuals and the fate of infected ants when loosing their vaccination potential will be determined, as well as the effects of Social Vaccination on disease spread in the colony and the regulation of collective defences between group members (PhD 2). This unique combination studying both the social and individual aspect of immune defences makes this project valuable for the fields of Social Evolution and Ecological Immunology, and further impacts on Epidemiology, Evolutionary Medicine and Biocontrol.

Keywords: collective anti-parasite behaviour,invertebrate immune systems,ecological immunology
Exploring the aggressiveness of prostate cancer to enable an individualised treatment approach (EXACTA)

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-2009-StG, 2009)
Start date: 2010-03-01
End date: 2015-02-28
Duration (months): 60.0
Total project cost (EUR): 1800209.0
EU funding (EUR): 1800209.0
Participants: 1
Project status: CLOSED

Prostate cancer is the most frequently diagnosed malignancy in the western male population and the associated socio-economic impact on healthcare is more than worrying. There is one key feature of confined (stage T2) prostate cancer that needs to be addressed with immediate urgency: its true aggressiveness. Not all cancers are life threatening and early diagnosis, although needed to improve outcome, will lead to overtreatment of patients with indolent prostate cancer resulting in unnecessary treatment-related morbidity. Therefore, methods to identify clinically significant forms of prostate cancer have to be developed. To pursue this, the initial assessment of the extent of the disease process (clinical staging) needs to be adequate. Obtaining pre-treatment representative tumor tissue (biopsies) is a major clinical challenge, as the disease is often multi-focal and heterogeneous. Accurate functional in vivo imaging modalities could guide these biopsies. Modern genomics technologies have identified numerous cancer cell-associated genetic markers being expressed in prostate cancer tissue or body fluids. Closing the gap between genomics and a non-invasive metabolic assessment of the in vivo prostate, we propose to identify new in vivo targets/biomarkers indicating confined prostate cancer aggressiveness with the underlying central hypothesis: early functional metabolic differences in different tumor foci determine whether it will grow into life-threatening prostate cancer or not. To track these early metabolic differences, the very latest magnetic resonance methodologies, including 13C MR of hyperpolarized metabolites and 1H- and 31P-MRSI of the in vivo human prostate at a field strength of 7 Tesla, will be further developed and implemented. In the well-established translational research environment at the host institution, potential new biomarkers translate into molecular diagnostics or imaging tools for an accurate individual assessment of cancer aggressiveness.

Keywords: metabolism,magnetic resonance imaging,magnetic resonance spectroscopic imaging,x-nuclei
Development of super-wheat crops by introgressing agronomic traits from related wild species (SWCD)

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: Spain
Call:  (ERC-2009-StG, 2009)
Start date: 2010-01-01
End date: 2015-12-31
Duration (months): 72.0
Total project cost (EUR): 600000.0
EU funding (EUR): 600000.0
Participants: 1
Project status: CLOSED

Wheat is one of the most important food crops in the world and understanding its genetics and genome organisation is of great value for genetics and plant breeding purposes. Despite is genome complexity (polyploidy), hexaploid and tetraploid wheats behave as diploids during meiosis. This means that each chromosome only recognises its identical (homologue) to pair and not the related chromosomes (homeologues). There are several pairing homologous (Ph) genes controlling chromosome pairing in wheat during meiosis. The strongest effect is associated with the Ph1 locus, which is located on the long arm on chromosome 5B. Ph1 appears to sense homology prior to the chromosomes coming into contact with each other at early meiosis. Thus, if the chromosomes are true homologues, they perfectly recognise each other, chromatin remodelling is synchronized and allows pairing and recombination to occur. If the chromosomes are homoeologous (related), remodelling is not synchronized and the chromosomes fail to pair and recombine. In the absence of Ph1, all chromosomes can remodel without the requirement for the presence of an identical or near identical chromosome, and this increases the chance of pairing between related chromosomes in addition to pairing between true homologues. In this project we want to analyse deeper this Ph1 behaviour and we also want to exploit ph1 mutants as a tool for wheat breeding programs to promote inter-specific recombination between related wild species. In fact, Hordeum chilense (wild barley with interesting agronomic traits for wheat breeding) introgressions will be developed into durum wheat to transfer desirable agronomic traits from this wild barley into wheat, like resistance to diseases or the increment in carotene content. Introgression lines will be crosses with ph1 mutants to promote inter-specific recombination H. chilense-wheat, reduce the size of the H. chilense chromosome fragment. New wheat varieties will be generated.

Keywords: wheat,h. chilense,meiosis,chromosome pairing,ph1,plant breeding
Tie2-expressing monocytes: Role in tumor angiogenesis and therapeutic targeting (TIE2+MONOCYTES)

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: Switzerland,Italy
Call:  (ERC-2009-StG, 2009)
Start date: 2009-11-01
End date: 2014-10-31
Duration (months): 60.0
Total project cost (EUR): 1311900.0
EU funding (EUR): 1311900.0
Participants: 2
Project status: CLOSED

Recent data indicated that tumor-infiltrating myeloid cells promote tumor angiogenesis. We contributed to this concept by showing that Tie2-expressing monocytes (TEMs) have a requisite role in this process. Indeed, the specific elimination of TEMs inhibits tumor angiogenesis and growth in several models. Yet, little is known of the biological bases of TEMs activity in tumors. Building upon my previous studies, I will provide a thorough characterization of the precise identity of TEMs and of their biological role in mouse tumor models. I will perform comparative gene expression studies and analyze the developmental relationship between TEMs and other monocyte-lineage cells. By exploiting state-of-the-art genetic strategies, including novel gene knockdown platforms and exogenously- and microRNA-regulated vectors, I will identify and validate molecular pathways that may be targeted to selectively inhibit TEMs activity in tumors. I recently showed that TEMs can be turned into efficient and therapeutically effective vehicles for the targeted delivery of interferon-alpha to tumors. I will now implement preclinical models, including human hematochimeric mice, that will better assess the safety and feasibility of this new delivery strategy. Finally, I will assess the relevance of TEMs in metastasis, and exploit them to constrain metastatic dissemination and growth, either by a cell depletion approach or by delivering interferon specifically at the metastatic niche. The results of these studies will increase significantly our knowledge of the biological functions of proangiogenic monocytes in tumor development, and may improve cancer therapies by enlightening novel and yet unrecognized therapeutic targets and by providing proof-of-feasibility of a new gene therapy strategy.

Keywords: tumor angiogenesis
Epigenetic and genome stability: non coding RNA-mediated chromatin modifications in S. cerevisiae (EPINCRNA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Genetics,Genomics,Bioinformatics and Systems Biology
Countries involved: France
Call:  (ERC-2009-StG, 2009)
Start date: 2009-12-01
End date: 2014-11-30
Duration (months): 60.0
Total project cost (EUR): 1735524.0
EU funding (EUR): 1735524.0
Participants: 1
Project status: CLOSED

Our project is to understand the role of non coding (nc)RNA in the regulation of epigenetic landscape and gene expression. RNA interference pathway is absent in the budding yeast but recent works from our laboratory showed the existence of an original ncRNA-dependent pathway that controls gene expression in S. cerevisiae. We characterized a cryptic unstable ncRNA mediating the transcriptional silencing of the transposon Ty1 through histone methylation. Furthermore, unpublished data suggest the existence of subtelomeric ncRNAs that might control telomere metabolism and promoter-associated ncRNAs that mediate repressive epigenetic marks. We propose that a class of unstable ncRNA mediates genome expression and fluidity through histone modifications. Following 2 directions, our aim is to systematically identify these ncRNAs (A) and further characterize their regulatory mechanisms (B). (A) First, we aim to identify the regulatory ncRNAs by performing genome-wide approaches in strains accumulating these regulatory ncRNAs. We envisage developing protocols to analyze the cryptic transcriptome using deep sequencing technologies. (B) Second, we will further characterize the previously identified regulatory ncRNAs controlling repetitive regions (Ty1 transposon and telomeric repeats) but also gene expression. Through a range of experimental procedures from living cell biology (Fluorescence Immuno Hybridization), biochemical approaches (RNA-TRAP) and genetic, we will determine the dynamics of the regulatory ncRNA within the cell, the associated proteins that regulate their activities and the chromatin defects resulting from their expression. Our aim is to extensively describe the RNAi-like regulation in S. cerevisiae, that we anticipate to be broadly conserved in other eukaryotes.

Keywords: chromatin,transcription,histone,rna
Balancing selection and the molecular evolution of mimicry supergenes (MIMEVOL)

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: France
Call:  (ERC-2009-StG, 2009)
Start date: 2010-02-01
End date: 2014-01-31
Duration (months): 48.0
Total project cost (EUR): 760726.0
EU funding (EUR): 760726.0
Participants: 1
Project status: CLOSED

How genome organisation and architecture respond to variations in selection regimes is indeed poorly known at the microevolutionary scale. Supergenes are tight clusters of genes which simultaneously control the variation of various components of a complex trait, involving elements with different ontology1-4. Supergenes typically evolve in response to strong epistatic selection between neighbouring genes. They are usually maintained by some form of balancing selection, but the modalities of their evolution are still obscure and require empirical investigation. I propose to take advantage of the remarkable supergene controlling wing-pattern mimicry balanced polymorphism in the tropical butterfly Heliconius numata to investigate the structure and evolution of supergenes at the molecular level. The supergene P is a positional homologue of a loose cluster of loci controlling wing pattern mimicry in a related species. Positional cloning revealed the supergene is situated in a local inversion. Recombination is largely suppressed around P and two groups of haplotypes segregate in perfect association with wing pattern in natural populations. I propose to investigate the detailed structure of the inversion breakpoints and gene shuffling to test the working model of supergenes arising by rearrangement of distant ancestral loci. Using population genetics I propose to survey genetic diversity and look for signatures of balancing selection on the genes composing the supergene inversion. We will test for the effect of balancing selection in a patchy habitat, which has received little empirical data. We are now very close to genetically characterise the major loci controlling spectacular adaptations, involved in speciation and radiations, and determining species coexistence.

Keywords: genetic architecture - adaptation - inversion - population genetics - lepidoptera