Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Functional and Mecahnistic Roles of Large Intergenic Non-coding RNAs in Cancer (CANCERLINC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: Spain
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2017-12-31
Duration (months): 72.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Mammalian cells express thousands of RNA molecules structurally similar to protein coding genes –they are large, spliced, poly-adenylated, transcribed by RNA Pol II, with conserved promoters and exonic structures –however lack coding capacity. Although thousands exist, only few of these large intergenic non-coding RNAs (lincRNAs) have been characterized. The few that have, show powerful biological roles as regulators of gene expression by diverse epigenetic and non-epigenetic mechanisms. Significantly, their expression patterns suggest that some lincRNAs are involved in cellular pathways critical in cancer, like the p53 pathway. I explored this association demonstrating that p53 induces the expression of many lincRNAs. One them, named lincRNA-p21, is directly induced by p53 to play a critical role in the p53 response, being required for the global repression of genes that interfere with p53 induction of apoptosis. My results, together with the emerging evidence in the field, suggest that lincRNAs may play key roles in numerous tumor-suppressor and oncogenic pathways, representing an unknown paradigm in cellular transformation. However, their mechanisms of function and biological roles remain largely unexplored. The goal of this project is to decipher the functional and biological roles of lincRNAs in the context of oncogenic pathways to better understand the cellular mechanisms of gene regulation at the epigenetic and non-epigenetic levels, and be able to implement lincRNA use for diagnostics and therapies. In order to accomplish these goals we will integrate molecular and cell biology techniques with functional genomics approaches and in vivo studies. Importantly, the profiling of patient samples will reveal the relevance of our findings in human disease. Together, the functional study of lincRNAs will not only be crucial for developing improved diagnostics and therapies, but also will help a better understanding of the mechanisms that govern cellular network.

Keywords: large non-coding rnas
Uncovering the Mechanisms of Epigenetic Reprogramming of Pluripotent and Somatic Cell States (CELLREPROGRAMMING)

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: Israel
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 1960000.0
EU funding (EUR): 1960000.0
Participants: 1
Project status: CLOSED

The generation of animals by nuclear transfer demonstrated that the epigenetic state of somatic cells could be reset to an embryonic state, capable of directing the development of a new organism. The nuclear cloning technology is of interest for transplantation medicine, but any application is hampered by the inefficiency and ethical problems. A breakthrough solving these issues has been the in vitro derivation of reprogrammed Induced Pluripotent Stem “iPS” cells by the ectopic expression of defined transcription factors in somatic cells. iPS cells recapitulate all defining features of embryo-derived pluripotent stem cells, including the ability to differentiate into all somatic cell types. Further, recent publications have demonstrated the ability to directly trans-differentiate somatic cell types by ectopic expression of lineage specification factors. Thus, it is becoming increasingly clear that an ultimate goal in the stem cell field is to enable scientists to have the power to safely manipulate somatic cells by “reprogramming” their behavior at will. However, to frame this challenge, we must understand the basic mechanisms underlying the generation of reprogrammed cells in parallel to designing strategies for their medical application and their use in human disease specific research. In this ERC Starting Grant proposal, I describe comprehensive lines of experimentation that I plan to conduct in my new lab scheduled to open in April 2011 at the Weizmann Institute of Science. We will utilize exacting transgenic mammalian models and high throughput sequencing and genomic screening tools for in depth characterization of the molecular “rules” of rewiring the epigenome of somatic and pluripotent cell states. The proposed research endeavors will not only contribute to the development of safer strategies for cell reprogramming, but will also help decipher how diverse gene expression programs lead to cellular specification during normal development.

Keywords: pluripotency,ips cells,epigenetic reprogramming,embryonic stem cells
Health Effects of Social Change in Gender, Work & Family: Life Course Evidence from Great Britain (SOCIALCHANGEHEALTH)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Institutions, values, beliefs and behaviour
Countries involved: United Kingdom
Call:  (ERC-2011-StG_20101124, 2011)
Start date: 2011-11-01
End date: 2016-10-31
Duration (months): 60.0
Total project cost (EUR): 681582.0
EU funding (EUR): 681582.0
Participants: 2
Project status: CLOSED

Immense changes in work and family lives of men and women are well-documented, but their relationship with health and wellbeing remains unclear. The aim of this study is to use data from four longitudinal British birth cohort studies to assess the health impact of social change in women's and men's work-family life courses, for both the women and the men themselves, but also for their children and partner's. Generational changes in these relationships will also be investigated as biographies diversify over time. The objectives of the study are: 1. To characterise cohort differences in women's and men's participation in paid work, unpaid domestic work and family forms in Britain using longitudinal typologies. 2. To examine gender differences in relationships between work-family typologies and health and whether these relationships differ by cohort. 3. To investigate whether relationships between work-family typologies and health vary by socioeconomic position for men and women in different cohorts. 4. To examine the effects of changing work and family patterns on children's emotional and physical development. 5. To investigate the extent to which changing relationships between work-family typologies and health are mediated by changes in the social relations of gender. State-of-the-art contributions will be four-fold: 1. The inclusion of biological measures of health, in addition to measures of perceived health, to examine the interface between the social (gender) and biological (sex) in national, longitudinal population studies. 2. The use of life course data across cohorts to examine generation and gender differences in the health effects of increasing individualization. 3. Investigating the health effects of social change within families, focusing on health effects among men and children in addition to women. 4. The application of sociological theory to quanitative social epidemiology.

Keywords: gender,work,family,social change,health,biomarkers
The role of ROS/RNS during inflammation-associated and sporadic carcinogenesis (ROSCAN)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Germany,Germany
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2011-10-01
End date: 2016-09-30
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 2
Project status: CLOSED

A link between inflammation and cancer has been suspected over a long period of time and in recent years genetic evidence supporting such notion could be obtained. Several signaling pathways, such as NF-κB and STAT3, could be identified by our group as well as other groups to play important roles during tumor promotion and progression. Chronic inflammation leads to the formation of reactive oxygen and nitrogen species, which are known to cause DNA damage and inactivation of DNA repair mechanisms, thereby presumably inducing tumor-initiating mutations. On the other hand, oxidative stress has been documented to trigger apoptosis and cellular senescence. However, in vivo evidence demonstrating the consequences of increased oxidative stress on tumor development in a distinct genetic model is lacking. Selenoproteins of the glutathione peroxidase and thioredoxin reductase family are important anti-oxidant scavenger systems. Using cell type specific inactivation (epithelial cells an myeloid cells) of several of these family members in various well established and relevant models of inflammation-associated and sporadic colon tumorigenesis we will directly examine the role of these anti-oxidant systems. These models will allow us to genetically determine the outcome of increased lipid peroxidation and accumulation of reactive oxygen species in each cell type and to address whether cancer development is supported or inhibited under such conditions and will help to identify which phase of tumor development is affected. Furthermore, we expect to obtain results that will determine whether increased levels of ROS/RNS found during chronic inflammation are capable of initiating tumorigenesis. Our proposed experiments are supposed to provide fundamental insight into the molecular changes in the tumor microenvironment, which will ultimately help to identify novel strategies to prevent and treat colorectal cancer.

Keywords: inflammation,ros,colon cancer,signal transduction
Terragenesis: Using landscape ontogeny to predict the persistence of species (TERRAGEN)

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: United Kingdom
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-01-01
End date: 2016-12-31
Duration (months): 60.0
Total project cost (EUR): 1486058.0
EU funding (EUR): 1486058.0
Participants: 1
Project status: CLOSED

Biodiversity scenarios have the potential to exert a strong influence on public perception of the current biodiversity crisis, and on national and international policies to mitigate that crisis. Here, I propose to generate a novel conceptual and analytical model of biodiversity loss, and combine that with deforestation models to generate biodiversity scenarios for the world’s most species rich ecosystem, the rainforests of the humid tropics. Studies of the ecological consequences of habitat fragmentation almost entirely ignore the historical patterns of landscape change that have led to habitat patches being distributed in the way they are. I have developed a simple random sampling model that shows how explicit consideration of landscape ontogeny generates a remarkably diverse set of testable predictions about biodiversity patterns in fragmented landscapes. The model, termed terragenesis, combines the random sampling hypothesis with a landscape terrageny, the latter representing the historical relationships between patches much as a phylogeny represents evolutionary relationships among species. I propose to extend the simple model based on the random sampling hypothesis to incorporate real-world complexity such as variation in rates and timing of historical habitat loss, spatial variation in habitat quality within patches, species dispersal among patches and the way in which matrix habitat influences those dispersal patterns, and variation among species in their susceptibility to habitat loss and fragmentation. I will combine the analytical biodiversity predictions with modelled scenarios of deforestation and logging damage across the humid tropics that my research group is already developing to generate biodiversity scenarios for the world’s most biodiverse biome.

Keywords: biodiversity scenario,habitat fragmentation,tropical deforestation
Large-scale integrative biology of human dendritic cells (IT-DC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: France
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-03-01
End date: 2017-02-28
Duration (months): 60.0
Total project cost (EUR): 1498996.8
EU funding (EUR): 1498996.8
Participants: 1
Project status: CLOSED

The immune system is composed of different cell types that work in a coordinated manner to maintain the integrity of the organism in situations of threats or danger. Dendritic cells (DC) act as sentinels in peripheral tissue and mucosal interfaces where they integrate a diversity of danger- and inflammation-associated stimuli, then migrate to secondary lymphoid organs, and instruct naïve CD4 T cells to differentiate into the appropriate effector T cells. Hence, they play a critical role in linking innate to adaptive immunity. Three important levels of complexity characterize the DC system: 1) DC integrate multiple stimuli within complex inflammatory microenvironments, 2) these signals induce a complex output response and modify the global state of DC (environmental plasticity), 3) DC exist in different subsets generated by distinct differentiation pathways (evolutionary selection). In this proposal, we use cellular and molecular immunology combined to computational biology and modeling to study these properties at the large-scale level, and understand their interdependence in controlling DC biology. We ask the following specific questions: WP1: How DC subsets integrate combinations of stimuli at the large-scale level; WP2: How single and multiple stimuli modify DC state over time (dynamic modeling); WP3: How the DC global state influences response to a given stimulus. These questions will be addressed using a data-driven strategy combining global unsupervised exploratory analysis, gene-by-gene analysis and modeling, experimental validation of testable hypothesis. Through this systems level integrative approach, we will dissect the complexity of DC reciprocal interactions with their complex microenvironment, and hope to unravel novel mechanisms and concepts determining DC function.

Keywords: inflammation,intracellular networks,transcriptome,dynamic modeling
Disarming bacterial weapons in the nucleus: functional study of Chlamydia nuclear effectors (NUCHLEAR)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Immunity and infection
Countries involved: France
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-07-01
End date: 2018-06-30
Duration (months): 72.0
Total project cost (EUR): 1491660.0
EU funding (EUR): 1491660.0
Participants: 1
Project status: CLOSED

The high prevalence of Chlamydia infections and the heavy burden they inflict on public health justify the search for novel therapeutic approaches directed against this pathogen. Research on this obligate intracellular bacterium is very difficult, due to substantial technical impediments. One current challenge is to identify bacterial proteins that are required for Chlamydia to survive and proliferate in the host and that could serve as targets in novel therapeutic strategies. In particular, the identification of bacterial proteins implicated in the microbe’s ability to persist in host cells is highly desirable, since current treatments fail to erradicate the resulting chronic infections. Our project is focused on the bacterial proteins that are secreted into the host cell during infection and translocate into the nucleus. Our preliminary work has already identified some of these “nuclear effectors” of Chlamydia. Targetting the “central system” of the host, these proteins are likely essential for infection. We will (i) identify all Chlamydia trachomatis nuclear effectors and define their frame of action (in time and space) during infection, (ii) identify the targets of the nuclear effectors and their roles in infection and (iii) test the hypothesis that nuclear effectors are necessary for the entry into and/or maintenance of the persistent state of infection. Addressing for the first time the full repertoire of “nuclear weapons” of an intracellular bacterium, we will uncover new interactions between the pathogen and the host. This work will lead to the development of rationally-designed drugs that inhibit the activity of the nuclear effectors, thereby disrupting the microbe’s ability to survive in the host. Beyond this medical aim, our study, which lies at the interface between microbiology, cell biology and genome biology, will provide new angles of study to each of these three disciplines and improve our understanding of fundamental cellular processes.

Keywords: chlamydia,intracellular bacteria,host/pathogen interaction,type iii secretion,nucleus,nuclear functions
Controlling excitability in developing neurons: from synapses to the axon initial segment (CEIDNFSTTAIS)

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: 2012-03-01
End date: 2017-02-28
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

A critical question in neuroscience is to understand how neurons wire up to form a functional network. During the wiring of the brain it is important to establish mechanisms that act as safeguards to control and stabilize neuronal excitability in the face of large, chronic changes in neuronal or network activity. This is especially true for developing systems that undergo rapid and large scale forms of plasticity, which could easily lead to large imbalances in activity. If left unchecked, they could lead the network to its extremes: a complete loss of signal or epileptic-like activity. For this reason neurons employ different strategies to maintain their excitability within reasonable bounds. This proposal will focus on two crucial sites for neuronal information processing and integration: the synapse and the axon initial segment (AIS). Both sites undergo important structural and functional rearrangements in response to chronic activity changes, thus controlling the input-output function of a neuron and allowing the network to function efficiently. This proposal will explore novel forms of plasticity that occur during development and which are key to establishing a functional network. They range from understanding the role of activity during synapse formation to how pre- and postsynaptic structure and function become matched during development. Finally, it tackles a novel form of plasticity that lies downstream of synaptic inputs and is responsible for setting the threshold of action potential firing: the axon initial segment. Here, chronic changes in network activity results in a physical relocation of the AIS along the axon, which in turn alters the excitability of the neuron. This proposal will focus on the central issue of how a neuron alters both its input (synapses) and output (AIS) during development to maintain its activity levels within a set range and allow a functional network to form.

Keywords: synaptogenesis,homeostatic plasticity,presynaptic,postsynaptic
How force regulates cell function: a molecular and cellular outlook (FORCEREGULATION)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Molecular and Structural Biology and Biochemistry
Countries involved: United Kingdom
Call:  (ERC-2011-StG_20101109, 2011)
Start date: 2012-03-01
End date: 2018-02-28
Duration (months): 72.0
Total project cost (EUR): 1998331.0
EU funding (EUR): 1998331.0
Participants: 2
Project status: CLOSED

Force is ubiquitous in nature and physical stimuli are crucial for cell function. How cells process forces determines key physiological processes such as cell growth and differentiation, in which cells divide or differentiate according to the chemical and physical cues cells receive from the extracellular matrix. Physical stimuli have also been involved in the development of pathological processes, especially those in which cells lose the proper physical communication with the environment, such as cancer and metastasis formation. The major components of the mechanotransduction signaling pathways that transmit and translate these physical messages will most likely to be the molecules that directly sense force from the extracellular matrix. These molecules are integrins and the proteins that link them to the cytoskeleton. Here, I propose a multidisciplinary approach aimed to elucidate how force can modulate cellular behaviour. The project will focus on (i) determining how cells sense, produce and interpret forces and (ii) the cellular outcomes resulting from these processes. First, a nanotechnological suite composed of magnetic tweezers, and siRNA technology will be developed and employed to determine the roles of the molecules involved in these mechanical pathways. Second, the molecular mechanisms that trigger the interaction of proteins under force application will be studied. Several biophysical techniques such as magnetic tweezers, Atomic Force Microscopy (AFM), Total Internal Reflection Fluorescence (TIRF), and Fluorescence Resonance Energy Transfer (FRET) will be used here. Finally, a comparative study of the effect of force in normal and malignant cells will be accomplished. It will be tested whether or not these pathways are involved in the expression of genes in the nucleus, and the ability of normal and malignant cells to respond to external forces and to apply forces on their substrates. Magnetic tweezers, and elastic pillars will be used here.

Keywords: force regulation,mechanical stimulus,mechanotransduction,force sensing,transmission and transduction,talin,integrin,cytoskeletal proteins,from mechanical stimuli to biochemical signals