Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
THE ROLE OF UBIQUITYLATION AND DEUBIQUITINATION ENZYMES IN CANCER (UBIQCANCER)

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: Sweden
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-04-01
End date: 2016-03-31
Duration (months): 60.0
Total project cost (EUR): 1067280.0
EU funding (EUR): 1067280.0
Participants: 1
Project status: CLOSED

The overall goal of my research is to identify and characterize genetic factors leading to tumor development in human by establishing mouse models for development of anticancer drugs. The objective of the present study is to understand the function of ubiquitin ligation enzymes and deubiquitin enzymes during progression of different human skin cancers. This is analysed by generating transgenic animals and applying tumour-promoting protocol to specifically dissect the role of these enzymes during progression of cancer on mouse skin. During the proposed studies, mice deficient in various ubiquitin mediated signaling molecules such as CYLD and Bcl-3 will be used to test their contribution to cancer development. In addition we will identify novel E3 ligation and deubiquitination enzymes involved in progression of skin cancer using a multidisciplinary approach that combines mouse genetic, masspectrometry in vivo and gene expression profiling. To correlate information obtained from animal model to the development of treatments of human cancer, we are generating human tissue platforms from skin cancer patients regenerated on immune deficient mice. This model enables to study human epithelial neoplasms under in situ conditions. The results obtained in the transgenic animals as well as human tissue platform are correlated and compared to the samples from melanoma and non-melanoma human cancer patients. Furthermore, transgenic animals and transplanted human tissues are treated with proposed drug before tumor induction to test their specificity. Using state-of-the-art approaches and techniques, this project will identify novel markers for improved diagnosis and validation of candidate drug target for skin cancer therapies.

Keywords: skin cancer,ubiquitin,mouse genetic
Geometric control of the cell cycle in the fission yeast (GEOMETRYCELLCYCLE)

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: Switzerland
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-09-01
End date: 2016-08-31
Duration (months): 72.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Cell cycle progression is monitored by checkpoints that ensure the fidelity of cell division and prevent unrestricted cell proliferation. Checkpoints also serve to couple cell size with division – a mechanism important to adapt to changing environmental conditions. While most studies on cell size homeostasis have focused on the links between size and biosynthetic activity, we have recently discovered a novel geometry-sensing mechanism by which fission yeast cells couple cell length with entry into mitosis. Conceptually, the system is remarkably simple: it is composed of a signal – the protein kinase Pom1 – forming concentration gradients from the ends of the cells, which inhibits a sensor – the protein kinase Cdr2, itself an activator of mitotic entry – placed at the cell equator. Since Pom1 concentration at the cell middle is higher in short cells than in long cells, this suggests a model where Pom1 inhibits Cdr2 until the cell has reached a sufficient length. These findings open a conceptually new way of thinking about cell size homeostasis and suggest that cell polarity and cell shape have important effect on cell cycle progression. The proposed project investigates the mechanisms and functional importance of this geometry-sensing system through four specific aims: Aim 1. Defining and modeling the molecular mechanisms of Pom1 gradient formation Aim 2. Dissecting the mechanisms of Pom1 action Aim 3. Investigating the influence of altered cell shape on cell proliferation Aim 4. Exploring the effect of environmental stresses to the Pom1-Cdr2 system By combining genetic, biochemical, physical, live-imaging and modeling approaches, this project will provide an integrated understanding of how cell geometry can be perceived at the molecular level and how this information is transduced to control cell proliferation. This work will have wide-ranging implication for our understanding of gradient formation, cell size homeostasis, and the role of cell polarity in proliferation. It will thus be of interest to cell, developmental and cancer biologists alike.

Keywords: fission yeast,cell cycle,cell polarity,concentration gradient,stress response
SEcreted Membrane vesicles: role in the therapeutic plasticity of neural StEM cells (SEM_SEM)

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,Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2010-12-01
End date: 2015-11-30
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 2
Project status: CLOSED

Compelling evidence exists that somatic stem cell-based therapies protect the central nervous system from chronic inflammation-driven degeneration, such as that occurring in experimental autoimmune encephalomyelitis and stroke. It was first assumed that stem cells directly replace lost/damaged cells, but it has now become clear that they are able to protect the damaged nervous system through mechanisms other than cell replacement. In immune-mediated experimental demyelination and stroke we have shown that transplanted NPCs possess a constitutive and inducible ability to mediate efficient bystander myelin repair and axonal rescue. Yet, a comprehensive understanding of the mechanisms by which NPCs exert their therapeutic impact is lacking. We envisage that major NPC functions would result from highly sophisticated horizontal communication and we attribute a key role to the transfer of secreted membrane vesicles (MVs) from NPCs to neighbouring cells. Here we will focus on defining whether this form of communication exists for NPCs, and on elucidating its molecular signature and therapeutic relevance. We will investigate the MV small RNAome using next generation deep-sequencing, computational analysis and bioinformatics tools; and demonstrate that ncRNAs from NPCs are able to affect gene expression in neighbouring cells. Functional readouts of candidate ncRNAs will be provided by semi-quantitative RT-PCR and cutting-edge molecular and cellular biology tools [eg., miRNA-regulated LV vectors; identification of ncRNA targets by quantitative proteomics] on recipient cells. Then, we will demonstrate the biological impact of the transfer of individual small ncRNAs in vitro and in vivo in rodents with experimental neurological diseases. The true innovation of this project relies in its unique peculiarity to look into an innate mechanism with the visionary focus of translating the knowledge of basal stem cell functions into innovative high clinical impact therapeutics.

Keywords: neural stem cells,membrane particles,stem cell therapies,horizontal rna transfer,mirnas,small ncrnas.
Neurocircuitry of endocannabinoid regulation of food intake (ENDOFOOD)

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: France
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-02-01
End date: 2016-01-31
Duration (months): 60.0
Total project cost (EUR): 1500000.0
EU funding (EUR): 1500000.0
Participants: 1
Project status: CLOSED

Few tasks executed by the brain hold greater survival and adaptive value than keeping us fed and in adequate nutritional state. The regulation of energy metabolism represents a prototypical homeostatic system, with the brain acting as the central coordinator. Any alteration of these mechanisms can lead to pathological states threatening the survival of the individual. The main brain region regulating food intake behaviour is the hypothalamus. The endocannabinoid system (ECS), formed by cannabinoid receptors, their endogenous ligands (endocannabinoids) and the enzymatic machinery for the synthesis and degradation of endocannabinoids is centrally involved in the regulation of food intake. This project aims at defining the mechanisms of the ECS-mediated control of food intake. We will reach the following goals: 1.We will generate advanced genetic tools allowing conditional deletion, rescue and overexpression of ECS elements. The integrated use of these tools will lead to the detailed mapping of the brain neurocircuitries where the ECS controls food intake. 2.We will provide strong evidence pointing to differential functions of the ECS in food intake, depending on the specific circuits activated. 3.We will determine which endocannabinoid(s) are involved in specific aspects of food intake. 4.We will detail the electrophysiological impact of the ECS on the hypothalamic neuronal network regulating food intake. 5.We will identify novel biochemical mechanisms, linking the ECS to hypothalamic neuronal activity, mitochondrial functions and regulation of food intake. This project has the ambitious aim to explore new scientific avenues and to provide “in depth” knowledge on the neuronal mechanisms regulating ingestive behaviour in mammals. The results of this project will pave the way to novel lines of research for the physiology and pharmacology of the ECS in the control of energy balance.

Keywords: endocannabinoid system,food intake,conditional mutagenesis
Brain states, synapses and behaviour (BRAINSTATES)

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: Germany
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-02-01
End date: 2016-01-31
Duration (months): 60.0
Total project cost (EUR): 1463125.0
EU funding (EUR): 1463125.0
Participants: 1
Project status: CLOSED

Global changes in patterns of neuronal activity or brain state are the first phenomenon recorded in the awake human brain (1). Changes in brain state are present in recordings of neocortical activity from mouse to man. It is now thought that changes in brain state are fundamental to normal brain function and neuronal computation. Despite their importance, we have very little idea about the underlying neuronal mechanisms that generate them or their precise impact on neuronal processing and behaviour. In previous work we have characterised brain state changes in a well characterised model for neuroscience research the mouse whisker system. We have recorded changes in the brain state in mouse cortex during whisker movements (2). In this proposal, we aim to use the mouse whisker system further to investigate the mechanisms and functions of changes in brain state. First we will use state of the art techniques to record and manipulate neuronal activity in the awake, behaving mouse to investigate the network and cellular mechanisms involved in generating brain state. Second we will use 2-photon microscopy to investigate the impact of brain state on excitatory and inhibitory synaptic integration in vivo. Finally we will use behaviourally trained mice to measure the impact of brain state changes on sensory perception and behaviour. This proposal will therefore provide fundamental insights into brain function at every step: mechanisms of changes in brain state, how neurons communicate with eachother and how the brain controls sensory perception and behaviour. References 1 Berger H (1929) Archiv für Psychiatrie und Nervenkrankheiten 87:527-570. 2 Poulet JFA, Petersen CC (2008) Nature 454:881-885.

Keywords: cortex,behaviour,electrophysiology,optogenetics
EUROmediCAT: Safety of Medication use in Pregnancy in Relation to Risk of Congenital Malformations (EUROMEDICAT)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Collaborative project
Countries involved: United Kingdom,Netherlands,United Kingdom,Denmark,Poland,Italy,United Kingdom,United Kingdom
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2011-03-01
End date: 2015-02-28
Duration (months): 48.0
Total project cost (EUR): 3956151.6
EU funding (EUR): 2996100.0
Participants: 9
Project status: CLOSED

A variety of complementary approaches are needed to evaluate safety of medicine use in pregnancy. To evaluate safety in relation to teratogenicity (capacity to cause malformations), population-based congenital anomaly registers, which are already networked across Europe (EUROCAT) with a common database, can provide a cost-effective mechanism which is as yet underexploited. The enormous population coverage of registers when combined gives sufficient statistical power for the identification of associations between specific drugs and specific malformations. This project will develop and test an efficient pharmaco-vigilance system for safety of drugs during pregnancy in relation to teratogenicity by (i) enhancing the information regarding drug exposure in the EUROCAT database, covering a total population of 3 million births 1995-2010, through linkage to electronic databases containing prescription information, and by linkage to chronic disease cohorts (ii) analysing the enhanced EUROCAT database in relation to four drug groups of public health concern - new antiepileptics, insulin analogs, SSRI antidepressants, and antiasthmatics - exposure to all of which is increasing in the pregnant population (iii) interrogating health care databases to monitor the effectiveness of drug safety recommendations and pregnancy prevention programmes through drug utilisation studies, and to provide an exposure profile for pregnant women (iv) conducting a scoping study of the implications for drug safety of growing internet use by pregnant women, in terms of access to safety information about teratogenicity, and access to drugs with teratogenic potential.

Keywords: medication,pregnancy,safety,congenital malformations,teratogen
Glycomics by High-throughput Integrated Technologies (GLYCOHIT)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Ireland,Germany,Ireland,Sweden,France,Norway,Germany,Belgium,Spain,China,United States,Japan,Israel
Call:  (FP7-HEALTH-2010-single-stage, 2010)
Start date: 2011-01-01
End date: 2014-06-30
Duration (months): 42.0
Total project cost (EUR): 4874903.6
EU funding (EUR): 2993056.4
Participants: 15
Project status: CLOSED

Protein glycosylation is a post-translational phenomenon that is involved in most physiological and disease processes including cancer. Most of the known cancer-associated glycobiomarkers were discovered individually using liquid chromatography and mass spectroscopy. Though valuable, there is room for improvement in these approaches for the discovery phase. There is also a critical need for innovative, rapid, and high-throughput (HTP) technologies that will translate the discovery of cancer-associated glycobiomarkers from basic science to clinical application. The GlycoHIT consortium brings a highly experienced, innovative and interdisciplinary team of researchers from Europe, China and USA representing academia, industry and clinical fields to significantly enhance some of the existing glycoanalytical technologies and to advance novel HTP glycoanalytical technologies beyond current state of the art. ▪ Microchip technology and novel partitioning methods will be exploited for nanoscale HTP separations of serum glycoproteins for analysis by HPLC or LC–MS. ▪ In parallel, lectin array technology will be radically improved by the innovative use of recombinant human lectins and lectin mimics derived by screening large phage displayed combinatorial libraries. ▪ Aptamer libraries will be exploited for identification of lectin mimics and development of a glycosignature platform ▪ Compatibility of the lectin/lectin mimic array technologies with novel label-free biosensors will be explored. Newly-developed technologies will be validated by analysis of serum samples from a variety of cancer patient cohorts and will be supported throughout by experimental interaction analysis, complex structural modelling and informatics. Effective project management, commercially-aware intellectual property management and targeted dissemination activities supplement the core science and ensure maximum impact for the project.

Keywords: glycomics,analysis,high-throughput,lectins,technologies,cancer
Modulation of mitochondrial complex I as a strategy to increase lifespan and prevent age-related diseases (COMPLEXI&AGING)

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: United Kingdom,Finland
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-02-01
End date: 2016-09-30
Duration (months): 68.0
Total project cost (EUR): 1491600.0
EU funding (EUR): 1491600.0
Participants: 2
Project status: CLOSED

Nowadays, ageing is one of the main problems in Western society. The increase in the percentage of elderly people serves to strain the Social Security to the point of bankruptcy. The only way to alleviate the suffering caused by age-related degenerative disease is to fully understand the underlying forces which drive ageing and design strategies to delay it. Mitochondria are considered as central modulators of longevity in different species. It has been proposed that free radicals cause the accumulation of oxidative damage and as a result ageing. In accordance with this, production of Reactive Oxygen Species (ROS) by complex I negatively correlates with longevity. However, the overexpression of antioxidants or the reduction of ROS levels does not increase lifespan. These contradictory data can only be reconciled if complex I is modulating longevity through a ROS independent mechanism. We have expressed the alternative internal NADH dehydrogenase 1 (NDI1) from Saccharomyces cerevisiae in Drosophila melanogaster. The expression of NDI1 does not change the level of ROS but increases both the ratio of NAD+/NADH and Drosophila longevity. The main objective of this proposal is to study the mechanisms by which complex I regulates longevity. My general hypothesis is that complex I regulates longevity through a ROS independent mechanism. I propose that complex I controls the cellular levels of NAD+/NADH, keeping their levels at an equilibrium that favours the optimal functioning of the cell. When the ratio is moved towards NADH ageing is promoted, whereas when it is moved towards NAD+ pro-survival pathways are activated. I proposed two specific mechanisms downstream of complex I that promote cellular longevity or senescence: 1) activation of sirtuins, which would increase genome stability and 2) reduction of methylglyoxal generation, which would decrease the accumulation of cellular garbarge .

Keywords: ageing,mitochondria,drosophila,lifespan,complex i,electron transport chain,ros,nadh
Host molecular and cellular responses to anti-cancer drug treatment as a potential biomarker for treatment outcome. (HOSTRESPONSE)

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: Israel
Call:  (ERC-2010-StG_20091118, 2010)
Start date: 2011-03-01
End date: 2017-02-28
Duration (months): 72.0
Total project cost (EUR): 1499622.0
EU funding (EUR): 1499622.0
Participants: 1
Project status: CLOSED

Chemotherapy remains one of the most common treatment modalities for cancer. It is typically administered in cycles of bolus injections following 21 days of drug-free break periods. However, tumor regrowth between drug intervals is often observed, due in part, to rebound angiogenesis. Our previous studies demonstrated that bone marrow derived proangiogenic cells are acutely mobilized following certain chemotherapy treatments, accompanied by enhanced tumor angiogenesis, which can be blocked by prior treatment with antiangiogenic drugs. These findings indicate that unknown host-derived mechanisms induced by chemotherapy, can stimulate tumor growth. Since the efficacy of antiangiogenic drugs is dependent on several parameters such as tumor type, stage, and the type of chemotherapy, such a therapy is not beneficial for all patients, and thus, necessitates the identification of surrogate biomarkers to predict clinical outcome. To address this issue, we will integrate basic, translational, and clinical approaches to: (i) identify molecular and cellular host systemic responses following treatments; (ii) isolate novel factors by proteomic approaches which are altered during the course of the treatment, and evaluate their feasibility as biomarkers to predict clinical outcome; (iii) determine the relevance of these factors in clinical specimens; (iv) screen for therapeutic compounds which can block host responses mediating tumor growth in order to increase treatment efficacy. We believe that this strategy of combined approach will lead to the development of new tools in clinical oncology. Profiling individual host response to anti-cancer drug treatment may serve as a biomarker for treatment outcome and further promote the concept of personalised medicine in cancer therapy.

Keywords: cancer therapy,antiangiogenic drugs,bone marrow derived cells