Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Evolutionary Social Ecology in Wild Populations (SOCECOL)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Evolutionary, population and environmental biology
Countries involved: United Kingdom
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-04-01
End date: 2015-03-31
Duration (months): 60.0
Total project cost (EUR): 2485013.0
EU funding (EUR): 2485013.0
Participants: 1
Project status: CLOSED

Social behaviour is ubiquitous, but most studies of wild populations treats individuals as if they are independent entities. The central thesis of this application is that our understanding of evolution and ecology is restricted by a failure to consider organisms in their social context. Novel analytical and technical approaches now enable a new generation of studies of organisms in their proper social context, and the quantification of the effects of social interactions. This proposal s central objective is to understand the dependence of a series of ecological processes on the social behaviour of interacting organisms, using replicate populations of model organisms for field population biology, tits (Parus). The research has four major aims: (1) To understand the causes and consequences of variation in social behaviour, using both individual (nodal) and population (network) approaches; (2) to conduct quantitative and molecular genetic analyses of social phenotypes, in particular considering the role of indirect genetic effects on both social and non-social phenotypes; (3) to conduct experimental manipulations, at a range of scales, of the social environment of individuals, and hence test their effect on population structure and dispersal; (4) to combine these approaches to understand how social interactions modulate the processes of dispersal and natural selection, and how they contribute to explaining fitness variance in these species. This combined approach, applied to one of the best studied populations of vertebrates in the world, will lead to major advances in our understanding of the determinants and forces acting on sociality, and in our understanding of the importance of social behaviour in modulating key ecological and evolutionary processes.

Keywords: social behaviour,dispersal,social networks,evolutionary quantitative genetics
Tissue engineering to evaluate novel treatments for skin cancer and genetic disease (TREATSKIN)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: United Kingdom
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-05-01
End date: 2015-04-30
Duration (months): 60.0
Total project cost (EUR): 1999999.12
EU funding (EUR): 1999999.12
Participants: 1
Project status: CLOSED

As our understanding of disease translates from basic science to clinical application there is a need for robust preclinical models to test interventions and therapies, which mirror the clinical situation and likely outcomes. This will assist key stage decision making before costly clinical trials are commenced. Skin diseases represent a significant health burden. Non-melanoma skin cancers including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common human malignancies. Genetic skin diseases, or genodermatoses, are heritable conditions comprising nearly 300 distinct often rare clinical entities, which affect ~30M people in Europe i.e. ~7% of the entire population (http://geneskin.idi.it/homepgs/rareg.php). Thus, genodermatoses have important medical and social implications and have very limited therapeutic possibilities. This proposal will develop preclinical models which can be used to identify therapeutic targets for the treatment of skin cancer and to explore novel approaches to gene and cell therapy. Organotypical tissue engineered skin constructs combining normal, malignant and diseased epithelial, mesenchymal and connective tissue elements will first be used to examine the effect of tumour microenvironment on cancer cell invasion. Then constructs mimicking 1. intraepithelial, 2. well and 3. poorly differentiated SCCs will be used as surface xenotransplants. Optimisation will examine the contribution of adipocyte and mesenchymal stem cells. A set of genes identified as a characteristic SCC signature by extensive previous studies will then be genetically manipulated to examine the effects of up and down regulation of these genes in tumour progression and invasion. The effects of novel small molecules will also be tested. Surface xenotransplants of organotypical cultures of genetically diseased keratinocytes will be established to assess the long term outcomes of comparing ex vivo gene therapy with protein and cell therapy.
Identifying the genes responsible for the expansion of the human cerebral cortex (NEUROMAN)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: ERC Advanced Grant Interdisciplinary Panel
Countries involved: Germany
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-10-01
End date: 2016-09-30
Duration (months): 72.0
Total project cost (EUR): 2496000.0
EU funding (EUR): 2496000.0
Participants: 1
Project status: CLOSED

The goal of this research proposal is to unravel the molecular and cell biological basis underlying the expansion of the human cerebral cortex. Specifically, we wish to identify the genes responsible for the increase in the generation of cortical neurons from neural stem and progenitor cells that occurs during primate evolution. We will take two complementary approaches. One is to characterize the differences between mouse and human cerebral cortex with regard to the molecular and cell biological features of neural stem and progenitor cells, their mode of division, and the generation of neurons from these cells. Among the observed differences, human-specific features of cortical progenitor cells will then be identified by comparison with various non-human primates. The resulting candidate genes will be expressed in mouse embryonic cortical progenitors by in utero electroporation and tested for their ability to reconstitute human-like cortical progenitors in vivo. The second approach is based on a novel technology that allows us to introduce the total pool of mRNAs expressed in human cortical progenitors into mouse cortical progenitors in organotypic slice culture. This technology will be used to functionally screen for human genes able to generate human-like cortical progenitors in the mouse embryonic cortex. Human genes validated by these two approaches will then be used to generate acute transgenic mouse embryos and transgenic mouse lines that show a gyrencephalic, primate-like cerebral cortex. This research proposal will provide fundamental insight into the process of human cortical expansion, which provides the cellular basis of higher brain function, and establish an essential basis for future progenitor cell-based therapies for the diseased human brain.

Keywords: none
Voxel Imaging PET Pathfinder (VIP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Spain
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-07-01
End date: 2015-06-30
Duration (months): 60.0
Total project cost (EUR): 2044400.0
EU funding (EUR): 2044400.0
Participants: 1
Project status: CLOSED

Positron-Emission-Tomography (PET) scanners play an important role in cancer diagnosis and molecular imaging. Their accuracy overtakes that of the conventional diagnostics systems. They are used, alone or in combination with other imaging systems, such as CT or MRI. The current best detectors for PET are based on LSO crystals that are usually made of 4mm x 4mm x 10mm coupled to PMT, APD, or similar photon-sensitive device. At best, the FWHM that can be achieved at 511keV is around 10%. This limited energy resolution limits the ability to remove scattered events which are a significant noise contribution to the reconstructed image. The typical length (in the radial direction) of the LSO crystals is about 10mm, which implies a significant uncertainty of the impact point in the radial direction and this induces an error in the projection of the Line of Response. This error deteriorates the quality of the reconstructed image. Pixel-PET uses pixel solid-state-detector coupled to front end electronics. With this novel detector one can achieve the followings: 1- millimeter-size voxel, this means no more parallax effect and hence precise LOR; 2-FWHM energy resolution of less than 1% for 511keV photons. This allows us to eliminate most of the scattered events and thus keep the golden events; 3- Have adequate depth of absorption to achieve high detection efficiency (90%) for 511keV photon; 4- The modular detector has trapezoidal parallelepiped shape thus making it seamless compared to the existing PET system; 5- The conceptual design can be modified to construct a Flat panel detector (Gamma Camera); 6-The design is compatible with MRI making it ideal for Brain imaging. Preliminary Geant4 simulation results, using Derenzo Phantom with Pixel-PET detector suggests that one can achieve the same image quality of the current PET devices but using 25 times less dose.

Keywords: molecular imaging,cancer,diagnostic,pet-mri
OVErcoming Resistance to anti-HER2 therapy (OVER-HER2)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Spain
Call:  (ERC-2009-AdG, 2009)
Start date: 2011-01-01
End date: 2014-12-31
Duration (months): 48.0
Total project cost (EUR): 1666700.0
EU funding (EUR): 1666700.0
Participants: 1
Project status: CLOSED

HER2 is a membrane receptor tyrosine kinase overexpressed in 30% of breast tumors and results in an aggressive clinical course. Anti-HER2 therapies including monoclonal antibodies (trastuzumab) and small-molecule tyrosine kinase inhibitors (lapatinib) are active and have improved survival of patients with HER2 overexpressing breast cancer. However, the emergence of primary or acquired resistance to these agents limits their efficacy. We have previously identified mechanisms of resistance to anti-HER2 therapies such as the co-expression of a truncated form of HER2 that correlates with trastuzumab resistance or the presence of downstream oncogenic mutations of PI3K or PTEN loss that result in resistance to lapatinib . Not surprisingly, PI3K/mTOR inhibitors overcome lapatinib resistance in the later example. Building on our results to date, this proposal is aimed at identifying novel mechanisms of resistance to anti-HER2 agents and to devise therapeutic strategies to revert it. To uncover such mechanisms, we have generated cancer cells with acquired resistance to lapatinib or trastuzumab by continuous exposure to increasing concentrations of these agents. We will perform genome wide screens, including shRNA libraries, gene expression and SNPs arrays, to discover candidate genes responsible for decreased sensitivity to anti-HER2 agents. To overcome anti-HER2 therapy resistance we will study several therapeutic strategies, such as combinations of different anti-HER2 compounds and the use of alternative agents targeting downstream/parallel pathways. Among the novel targeted therapies, we plan to study the use of PI3K, Akt, CDK2 and Hsp90 inhibitors, for which we will also start resistance-screens. It is anticipated that any promising preclinical leads will stimulate trial design and conduct for subsequent evaluation and confirmation in the clinic.

Keywords: her2 targeted therapy therapy resistance
Host-environment interactions in the protection from asthma and allergies (HERA)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Germany
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-05-01
End date: 2015-04-30
Duration (months): 60.0
Total project cost (EUR): 2155697.0
EU funding (EUR): 2155697.0
Participants: 1
Project status: CLOSED

Asthma and allergies are chronic conditions affecting billions of Europeans. These complex diseases are determined by interplay of genetic and environmental factors. Treatments can control symptoms, but cannot cure or prevent the diseases. I, and my team, have shown that children are strongly protected from asthma and allergies when growing up in a farming environment rich in microbial exposures: the prevalence of asthma and hay fever is reduced over 5 fold. We have shown that environmental exposure to microbial compounds is inversely related to asthma and allergies. We have isolated microbes from animal sheds which protect mice from allergic airway inflammation. My team is now at a critical point to move this work forward to the next step, which is to systematically identify the microbes and their immuno-stimulatory compounds that protect from asthma and allergies. We have key resources in hand. In previous population based studies large numbers of environmental samples from farm and non farm children with and without asthma and allergies have been stored in biobanks. Genome wide genotyping data have also been gathered. The HERA project aims at applying the latest innovative high throughput sequencing techniques to comprehensively characterize the microbial ecology of these environmental samples. New methods for assessing microbial immuno-stimulatory substances will be used. These innovations will allow the HERA team to identify distinct asthma and allergy protective microbial exposures taking each individual s genetic susceptibility into account. Once protective microbial exposures have been identified, the responsible substances can be isolated. These substances can be developed into novel and effective prevention strategies to combat the asthma and allergy epidemic.

Keywords: epidemiology,environment,asthma,allergies,microbiology
Cell compartmentalization, individuation and diversity (BARRAGE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: Switzerland
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-05-01
End date: 2015-04-30
Duration (months): 60.0
Total project cost (EUR): 2200000.0
EU funding (EUR): 2200000.0
Participants: 1
Project status: CLOSED

Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.

Keywords: asymmetric cell division
THE HYGIENE HYPOTHESIS : REVISITING THE CONCEPT BY INTEGRATING EPIDEMIOLOGY AND MECHANISTIC STUDIES (HYGIENE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: France,Italy
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-08-01
End date: 2015-07-31
Duration (months): 60.0
Total project cost (EUR): 2099999.0
EU funding (EUR): 2099999.0
Participants: 2
Project status: CLOSED

The hygiene hypothesis postulating the paradoxical protective role of infections on immune-mediated diseases including atopy (i.e. atopic dermatitis, rhinitis, asthma) and more recently autoimmune diseases has been the matter of extensive investigation. The aim of the present project is to validate this hypothesis integrating epidemiological and experimental studies. We will review in a meta-analysis published studies of direct and indirect markers of infections and atopic diseases, and conduct a case-control study to analyse the association between infections and atopy using atopic dermatitis as a prototypic model. This epidemiological study will assess the occurrence of different infections and other risk factors related to the incidence of atopic dermatitis in children under age five in Italy (300 cases and 600 controls). This epidemiological study will be supported by experimental approaches addressing mechanistic questions raised by the hygiene hypothesis. Experimental models will include induction of acute and chronic bronchoconstriction/asthma, atopic dermatitis. In addition the project will aim at devising new mouse models of atopy. The nature of infections providing protection against allergic diseases will be investigated to characterise the difference at the molecular level between protective and non protective pathogens or their derivatives. The underlying immune mechanisms notably homeostasis imbalance, antigenic competition, stimulation of regulatory immune cells and Toll-like receptor involvement will be analysed. In addition to developing integrated in vivo models, including the use of transgenic animals, efforts will be focussed on the study of available synthetic pathogen-derived compounds showing a protective activity to better approach their cellular and molecular mode of action. These studies may pave the way to novel and safe therapies that could advantageously substitute for the “protective” immune stimulation induced by major infections.

Keywords: allergy,atopic dermatitis,asthma,infections,toll-like receptors,immunoregulation
Ras Genes in Health and Disease (RAS AHEAD)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Spain
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-04-01
End date: 2015-03-31
Duration (months): 60.0
Total project cost (EUR): 2496192.0
EU funding (EUR): 2496192.0
Participants: 1
Project status: CLOSED

Ras genes are some of the best-studied genes in biomedical research due to their central role in mitogenic signaling and their oncogenic activation in one third of all human tumors. More recently, Ras genes have also been implicated in developmental disorders including Costello and Noonan syndromes. In spite of this wealth of information, we still do not know the role of Ras proteins in adult homeostasis and, more importantly, how their misregulation affects human health. The latter is of paramount importance in order to develop efficacious therapies against tumors carrying Ras oncogenes - an achievement that could save thousands of lives worldwide. We propose to address these issues using genetic approaches in mouse models. We aim to systemically ablate all Ras genes in adult mice as well as in selective tissues to understand their role in normal homeostasis. We also propose to characterize mouse models for developmental disorders induced by hyperactive Ras proteins. These models should help us to better understand these human disorders as well as tools to test potential therapeutic strategies. Finally, we propose to use K-Ras driven mouse tumor models for human PDA and NSCLC to address key questions that may be directly translated to the clinic. In the case of PDA, we propose to study the contribution of the inflammatory response induced by pancreatitis to tumor development. In the case of NCSLC, we propose to isolate cancer initiating cells in an attempt to reveal the earliest events in tumor development. Moreover, we intend to use this tumor model to validate druggable Ras downstream effectors as therapeutic targets. The results derived from these studies should provide key information to design forthcoming clinical trials that will benefit cancer patients.

Keywords: ras oncogenes,mouse tumor models,target validation
Molecular origin and function of dynamic heterogeneities in mouse ES cells and pre-implantation embryos (MOFDH)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Cellular and Developmental Biology
Countries involved: United Kingdom
Call:  (ERC-2009-AdG, 2009)
Start date: 2010-05-01
End date: 2016-04-30
Duration (months): 72.0
Total project cost (EUR): 2299366.57
EU funding (EUR): 2299366.57
Participants: 1
Project status: CLOSED

The mechanisms powering the transition from one cell state to another are the central engine of embryonic development. Genetic analysis over the last twenty years has provided us with a catalogue of genes and proteins that can be linked in linear and time dependent manners to specific states and transitions in this process. However this picture, characterized by complex charts of univocal relationships between different genes, is static and rigid and contrasts with the plasticity displayed by cells in many processes, in particular during repair and regeneration. The early mammalian embryo and the closely related ES cells provide extreme examples of this in the form of toti- and pluri-potency i.e. the maintenance of an open uncommitted state from which all cell types emerge. Understanding the molecular basis of these uncommitted states and the way they are established and regulated will not only provide a deeper insight into the operation of biological systems but will also new targets for regulation and therapies. This project revolves around the hypothesis that the plasticity displayed by cells in developmental and regulative processes is associated with dynamical cellular heterogeneities generated by transcriptional noise: phenotypic variability in genetically identical cells that arises from stochastic fluctuations during transcription and translation. Specifically I propose to provide measurements and analysis of gene expression noise in mammalian cells, its origin, regulation and use using ES cells and early mouse embryos as experimental systems.

Keywords: quantitative biology,live imaging