Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Role of miRNAs in brown and white adipose tissue differentiation and function (MIRBATWAT)

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: Switzerland
Call:  (ERC-2013-StG, 2013)
Start date: 2014-02-01
End date: 2019-01-31
Duration (months): 60.0
Total project cost (EUR): 1400014.1
EU funding (EUR): 1400014.1
Participants: 1
Project status: CLOSED

Mammals have two types of fat: brown and white, with opposing functions. The white adipose tissue (WAT) is an important regulator of the whole body homeostasis that also serves to store energy in form of triglycerides (TGs). The main function of the brown adipose tissue (BAT) is to catabolize lipids in order to produce heat, a function that can be induced by cold exposure or diet. Disruption of the normal differentiation or development of the WAT causes ectopic lipid storage and severe pathology in both humans and experimental animals. Increased BAT development leads to increased energy expenditure without causing dysfunction in other tissues, and is associated with a lean and healthy phenotype, outlining the manipulation of the fat stores as an obvious therapeutic objective. With the proposed research we will identify miRNAs and other factors that regulate BAT and WAT differentiation and function. We will distinguish the miRNAs that specifically regulate brown or white adipogenesis and are expressed in the respective precursors, and establish them as signatures for either cell type. We will also identify the molecular mechanisms of action of the identified miRNAs in regulation of adipose tissue differentiation and metabolism. Using in vitro and in vivo systems, linage tracing studies, transgenic animals, as well as cohorts of human patients, we will determine the origin of the beige cells within the SAT, establish their importance in the regulation of metabolism in vivo, and develop novel strategies to induce the brown fat differentiation and function. Finally, we will discover ways to exclusively silence miRNAs in the brown fat will that will allow us not only to investigate the miRNAs function specifically in the brown fat, but also to develop new strategies for treatment of dyslipedaemia, diabetes and obesity.

Keywords: brown and white adipose tissue,micrornas,differentiation,preadipocytes,obesity,insulin sensitivity,metabolic diseases,glucose homeostasis
Neither visitors, nor colonial victims: Muslims in Interwar Europe and European Trans-cultural History (NEITHER NOR)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: The study of the human past
Countries involved: Netherlands
Call:  (ERC-2013-StG, 2013)
Start date: 2014-06-01
End date: 2019-05-31
Duration (months): 60.0
Total project cost (EUR): 1498984.0
EU funding (EUR): 1498984.0
Participants: 2
Project status: CLOSED

No comprehensive attempt has yet been made to cover the history of Muslims in interwar Europe. Historians of the modern Middle East underestimate the role of interwar Muslim actors in writing a history of Islam, whereas historians of Europe underestimate their role in intra-European developments. Existing works focus either on the nineteenth-century Muslim travelers, diplomats, students and residents or on the later post-World War II influx of Muslim immigrant workers. Based on personal and official archives, memoirs, press writings and correspondences, this project analyses the multiple aspects of the global Muslim religious, political and intellectual affiliations in interwar Europe, broadly defined. How did Muslims in interwar Europe act and interact among each other; and within the European socio-political and cultural context? The project answers this question by studying the intellectual and religio-political roles played by Muslim “intellectual agents” during the interwar years and up until the rest of World War II (1918-1946). We hypothesize that histoire croisée (entangled history) is the most appropriate approach to study the encounters and experiences of Muslim actors in interwar Europe from within. By exploring the complex relationship between the historical data and the social, political, theological and cultural patterns of Muslims as a new social structure in interwar Europe, the study represents a step towards a systematic global approach of Muslim connections in interwar Europe. The project contributes to our historical conceptualization of Europe itself as much as to our understanding of the contemporary scene of Islam in Europe and the world today, without resorting to a neatly tailored hypothesis. Many Muslim groups in the West nowadays still trace their heritage to the ideas of the great reformers of the early 20th century. More historical reflection on Islam in Europe can put the present “fear" for Islamization of the West into perspective.

Keywords: islamic studies religious studies
Towards a new understanding of carbon processing in freshwaters: methane emission hot spots and carbon burial (HYDROCARB)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Earth system science
Countries involved: Sweden
Call:  (ERC-2013-StG, 2013)
Start date: 2013-09-01
End date: 2019-08-31
Duration (months): 72.0
Total project cost (EUR): 1798226.6
EU funding (EUR): 1798226.6
Participants: 1
Project status: CLOSED

In spite of their small areal extent, inland waters play a vital role in the carbon cycle of the continents, as they emit significant amounts of the greenhouse gases (GHG) carbon dioxide (CO2) and methane (CH4) to the atmosphere, and simultaneously bury more organic carbon (OC) in their sediments than the entire ocean. Particularly in tropical hydropower reservoirs, GHG emissions can be large, mainly owing to high CH4 emission. Moreover, the number of tropical hydropower reservoirs will continue to increase dramatically, due to an urgent need for economic growth and a vast unused hydropower potential in many tropical countries. However, the current understanding of the magnitude of GHG emission, and of the processes regulating it, is insufficient. Here I propose a research program on tropical reservoirs in Brazil that takes advantage of recent developments in both concepts and methodologies to provide unique evaluations of GHG emission and OC burial in tropical reservoirs. In particular, I will test the following hypotheses: 1) Current estimates of reservoir CH4 emission are at least one order of magnitude too low, since they have completely missed the recently discovered existence of gas bubble emission hot spots; 2) The burial of land-derived OC in reservoir sediments offsets a significant share of the GHG emissions; and 3) The sustained, long-term CH4 emission from reservoirs is to a large degree fuelled by primary production of new OC within the reservoir, and may therefore be reduced by management of nutrient supply. The new understanding and the cross-disciplinary methodological approach will constitute a major advance to aquatic science in general, and have strong impacts on the understanding of other aquatic systems at other latitudes as well. In addition, the results will be merged into an existing reservoir GHG risk assessment tool to improve planning, design, management and judgment of hydropower reservoirs.

Keywords: limnology,carbon cycling,greenhouse gas emission,carbon burial,methane,carbon dioxide,natural organic matter,river damming,reservoirs
Re-engineering the tumor microenvironment to alleviate mechanical stresses and improve chemotherapy (REENGINEERINGCANCER)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Products and process engineering
Countries involved: Cyprus
Call:  (ERC-2013-StG, 2013)
Start date: 2014-01-01
End date: 2018-12-31
Duration (months): 60.0
Total project cost (EUR): 1440360.0
EU funding (EUR): 1440360.0
Participants: 1
Project status: CLOSED

Current chemotherapeutic agents are potent enough to kill cancer cells. Nonetheless, failure of chemotherapies for many cancers (e.g. breast and pancreatic cancers and various sarcomas) is primarily because these agents cannot reach cancer cells in amounts sufficient to cause complete cure. The abnormal microenvironment of these tumors drastically reduces perfusion and results in insufficient delivery of therapeutic agents. Tumor structural abnormalities is in large part an effect of mechanical stresses developed within the tumor due to unchecked cancer cell proliferation that strains the tumor microenvironment. Alleviation of these stresses has the potential to normalize the tumor, enhance delivery of drugs and improve treatment efficacy. Here, I propose to test the hypothesis that re-engineering the tumor microenvironment with stress-alleviating drugs has the potential to enhance chemotherapy. To explore this hypothesis, I will make use of a mixture of cutting-edge computational and experimental techniques. I will develop sophisticated models for the biomechanical response of tumors to analyze how stresses are generated and transmitted during tumor progression. Subsequently, I will perform animal studies to validate model predictions and indentify the drug that more effectively alleviates stress levels, normalizes the tumor microenvironment and improves chemotherapy. Successful completion of this research will reveal the mechanisms for stress generation and storage in tumors and will lead to new strategies for the use of chemotherapy.

Keywords: biomedical engineering,biomechanics,drug delivery,solid tumors,cancer pathophysiology,in vivo studies
LEarning from our collective visual memory to Analyze its trends and Predict future events (LEAP)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Computer science and informatics
Countries involved: France
Call:  (ERC-2013-StG, 2013)
Start date: 2014-11-01
End date: 2019-10-31
Duration (months): 60.0
Total project cost (EUR): 1496736.0
EU funding (EUR): 1496736.0
Participants: 1
Project status: CLOSED

People constantly draw on past visual experiences to anticipate future events and better understand, navigate, and interact with their environment, for example, when seeing an angry dog or a quickly approaching car. Currently there is no artificial system with a similar level of visual analysis and prediction capabilities. LEAP is a first step in that direction, leveraging the emerging collective visual memory formed by the unprecedented amount of visual data available in public archives, on the Internet and from surveillance or personal cameras - a complex evolving net of dynamic scenes, distributed across many different data sources, and equipped with plentiful but noisy and incomplete metadata. The goal of this project is to analyze dynamic patterns in this shared visual experience in order (i) to find and quantify their trends; and (ii) learn to predict future events in dynamic scenes. With ever expanding computational resources and this extraordinary data, the main scientific challenge is now to invent new and powerful models adapted to its scale and its spatio-temporal, distributed and dynamic nature. To address this challenge, we will first design new models that generalize across different data sources, where scenes are captured under vastly different imaging conditions. Next, we will develop a framework for finding, describing and quantifying trends that involve measuring long-term changes in many related scenes. Finally, we will develop a methodology and tools for synthesizing complex future predictions from aligned past visual experiences. Breakthrough progress on these problems would have profound implications on our everyday lives as well as science and commerce, with safer cars that anticipate the behavior of pedestrians on streets; tools that help doctors monitor, diagnose and predict patients’ health; and smart glasses that help people react in unfamiliar situations enabled by the advances from this project.

Keywords: visual recognition,dynamic scene analysis,visual prediction
Systematic in-vivo analysis of chromatin-associated targets in leukemia (CHROMATINTARGETS)

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: Austria
Call:  (ERC-2013-StG, 2013)
Start date: 2014-01-01
End date: 2019-12-31
Duration (months): 72.0
Total project cost (EUR): 1498985.0
EU funding (EUR): 1498985.0
Participants: 1
Project status: CLOSED

Recent advances in genome sequencing illustrate the complexity, heterogeneity and plasticity of cancer genomes. In leukemia - a group of blood cancers affecting 300,000 new patients every year – we know over 100 driver mutations. This genetic complexity poses a daunting challenge for the development of targeted therapies and highlights the urgent need for evaluating them in combination. One gene class that has recently emerged as highly promising target space are chromatin regulators, which maintain aberrant cell fate programs in leukemia. The dependency on altered chromatin states is thought to provide great therapeutic opportunities, since epigenetic aberrations are reversible and controlled by a machinery that is amenable to drug modulation. However, the precise mechanisms underlying these dependencies and the most effective and safe targets to exploit them therapeutically remain unknown. Here we propose an innovative approach combining genetically engineered leukemia mouse models and advanced in-vivo RNAi technologies to explore chromatin-associated vulnerabilities at an unprecedented level of depth. Following a first screen in MLL-AF9;Nras-driven AML, which led to the discovery of BRD4 as a promising therapeutic target, we aim to (1) construct a knockdown-validated shRNA library targeting 520 chromatin regulators and use it to comparatively probe chromatin-associated dependencies in diverse leukemia subtypes; (2) explore the mechanistic basis of response and resistance to suppression of BRD4 and new chromatin-associated targets; and (3) pioneer a system for multiplexed combinatorial RNAi screening and use it to identify synergies between established and new chromatin-associated targets. We envision that this ERC-funded project will generate a comprehensive functional-genetic dataset that will greatly complement ongoing genome and epigenome profiling studies and ultimately guide the development of targeted therapies for leukemia and, potentially, other cancers.

Keywords: leukemia,aml,all,mouse models,in-vivo rnai,multiplexed rnai screening,combinatorial rnai,therapeutic targets,chromatin network,brd4,epigenetic therapies,drug sensitivity and resistance
The Elementary Theory of Partially Commutative Groups (PCG)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Mathematical foundations
Countries involved: Spain
Call:  (ERC-2013-StG, 2013)
Start date: 2014-09-01
End date: 2019-08-31
Duration (months): 60.0
Total project cost (EUR): 1021216.8
EU funding (EUR): 1021216.8
Participants: 1
Project status: CLOSED

The solution of Tarski's problems on the first-order theory of free groups has uncovered deep connections between Model Theory, Geometry and Group Theory and served as a nexus and motivation for many classical results in Geometric Group Theory and Theoretical Computer Science. Just as the Tarski problems connected the theory of free groups with the geometry of trees, our goal is to point at a new direction in Group Theory and develop appropriate generalisations of the techniques and results whose nature is based on the geometry of higher dimensional counterparts of trees and interplays with the theory of partially commutative groups, notably the theory of groups acting on real cubings. We then shall apply these tools to approach fundamental questions in the model theory of partially commutative groups: classify finitely generated groups elementarily equivalent to a given partially commutative group and prove decidability and stability of their first-order theory.

Keywords: tarski problems,elementary equivalence of groups,right-angled artin groups,algebraic geometry over groups,model-theoretic stability
Identify novel pathways to enhance the induction of protective CD8+ T cell responses (PROTECTC)

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: Switzerland
Call:  (ERC-2013-StG, 2013)
Start date: 2013-10-01
End date: 2018-09-30
Duration (months): 60.0
Total project cost (EUR): 1499850.0
EU funding (EUR): 1499850.0
Participants: 2
Project status: CLOSED

There is an urgent need for progress in developing prophylactic and therapeutic vaccination strategies that induce polyfunctional, strongly protective cytotoxic CD8 T cell responses. These could shield us from pathogens against which the presently available, neutralizing antibody-inducing vaccine approaches confer limited or no protection and they could be used to eliminate tumors or chronic infections. In contrast to this need, we currently fail to induce effector and memory CD8 T cells in numbers high enough to effectively impact an infection or the growth of tumors. As protective CD8 T cell responses are readily generated during several viral infections, we need to improve our insight into how pathogen protection is naturally achieved, identify why immune protection sometimes fails, and use this knowledge to develop novel vaccine strategies. We will use a well balanced approach of hypothesis stimulated and unbiased multisystem observations to exploit novel mechanisms and to find ways to augment the CD8 T cell response to a vaccine. We have established model systems that are uniquely suited to extract and test molecules that determine T cell differentiation and expansion magnitude. Along with that we aim to enhance our insight of immune responses in vaccinated individuals to prevent creating situation in which vaccines fail to confer protection or may cause adverse effects. We recently made very unexpected observations that challenge our current concept of T cell differentiation in chronic infections, which proposes that T cells terminally differentiate and become senescent. We therefore aim to redefine our understanding of T cell responses in such infections. This will also be pursued to unravel novel strategies to reactivate T cells in persisting infections. Overall, the project will strongly further our insight into CD8 T cell responses during infections and will support the development of more effective vaccine strategies to induce antigen-specific CD8 T cells

Keywords: cytotoxic t cells,immune memory,acute infections,chronic infections,peptidemhc and tcr interaction,altered peptide ligands,secondary immune responses
Production Networks in Macroeconomics (MACRONETS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Individuals, institutions and markets
Countries involved: United Kingdom
Call:  (ERC-2013-StG, 2013)
Start date: 2014-05-01
End date: 2019-04-30
Duration (months): 60.0
Total project cost (EUR): 940200.0
EU funding (EUR): 940200.0
Participants: 1
Project status: CLOSED

A modern economy is an intricately linked web of specialized production units, each relying on the flow of inputs from their suppliers to produce their own output which, in turn, is routed towards other downstream units. Recent work in economics stresses that the structure of this production network is key in determining whether and how microeconomic shocks can propagate throughout the economy and shape aggregate outcomes. This project has two main goals. First, it aims to provide novel evidence that we can trace back the origins of business cycles and asset price fluctuations to individual technologies interconnected by input-supply relations. The particular questions it tries to answer are: (1) Can we have more direct, causal, evidence that these micro shocks do matter in practice for the evolution of aggregates? What are examples of these micro shocks in reality, how can we identify them and how do they propagate through input chains? (2) What are the asset pricing implications of this perspective on the micro origins of aggregate fluctuations? What is the relation between changes in the technology portfolio of an economy and the evolution of asset prices? The second aim of this project is to improve our understanding of the structure and evolution of these production networks by asking the following questions: (3) At the firm level, do more productive suppliers match with more productive customers and, if so, why? What is the typical duration of a supplier-customer match and does this vary across matches? What is the firm-level impact of matching with better suppliers or more productive customers? (4) How do inputs diffuse on a network of interconnected technologies? Do linkages across sectors facilitate input adoption and the diffusion of General Purpose Technologies? Can linkages across sectors help us understand not only which sectors will adopt a given input but also the order in which these sectors adopt it?