Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Releasing the brakes on adult plasticity (REBOOT)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: The Human Mind and its Complexity
Countries involved: Sweden
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-07-01
End date: 2019-06-30
Duration (months): 60.0
Total project cost (EUR): 1918069.8
EU funding (EUR): 1918069.8
Participants: 1
Project status: CLOSED

Age-related cognitive impairments compromise the functional capacity of aging individuals, and create major individual and societal costs. Developing means for preserving and restoring cognitive functioning in old age is therefore of great importance. Age-related cognitive impairments have a complex and multifactorial etiology. Pharmaceutical approaches to prevention and treatment have therefore been unsuccessful, and searching for non-pharmaceutical approaches is important. Results of cognitive training studies have so far been disappointing. I hypothesize that the reason for this is that plasticity is functionally inhibited after normal childhood development. Plasticity is then further reduced in aging due to negative brain changes. In this sense, past studies on the effects of cognitive training in adulthood and old age have, so to speak, attempted to push a car that has the brakes on. In a series of experimental studies on humans, my research team will discover feasible ways to release inhibitory brakes on adult plasticity, develop routes to attenuate age-related negative effects on plasticity, and uncover the neural mediators of training-related change in performance, so that the effects of cognitive training can be increased and better understood. Outcome variables include measures of brain function, volume, and integrity acquired using high-resolution magnetic resonance imaging, and up-to-date measures of cognitive performance. Experimental effects on these measures will be evaluated using structural equation models suitable for analyzing repeated measures. This amalgamation of state-of-the-art methodology in the neurosciences and the behavioral sciences bolsters the uniqueness of this research program, which will enlighten the mechanisms of plasticity at neuronal and behavioral levels of analysis. The resulting insights will pave the way for effective rehabilitation of several neurological conditions and for reducing age-associated cognitive impairments.

Keywords: plasticity,cognitive training,experience-dependent brain changes,aging,intervention
Aberrant RNA degradation in T-cell leukemia (ART)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Belgium
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-05-01
End date: 2019-04-30
Duration (months): 60.0
Total project cost (EUR): 1998300.0
EU funding (EUR): 1998300.0
Participants: 1
Project status: CLOSED

The deregulation of transcription is an important driver of leukemia development. Typically, transcription in leukemia cells is altered by the ectopic expression of transcription factors, by modulation of signaling pathways or by epigenetic changes. In addition to these factors that affect the production of RNAs, also changes in the processing of RNA (its splicing, transport and decay) may contribute to determine steady-state RNA levels in leukemia cells. Indeed, acquired mutations in various genes encoding RNA splice factors have recently been identified in myeloid leukemias and in chronic lymphocytic leukemia. In our study of T-cell acute lymphoblastic leukemia (T-ALL), we have identified mutations in RNA decay factors, including mutations in CNOT3, a protein believed to function in deadenylation of mRNA. It remains, however, unclear how mutations in RNA processing can contribute to the development of leukemia. In this project, we aim to further characterize the mechanisms of RNA regulation in T-cell acute lymphoblastic leukemia (T-ALL) to obtain insight in the interplay between RNA generation and RNA decay and its role in leukemia development. We will study RNA decay in human T-ALL cells and mouse models of T-ALL, with the aim to identify the molecular consequences that contribute to leukemia development. We will use new technologies such as RNA-sequencing in combination with bromouridine labeling of RNA to measure RNA transcription and decay rates in a transcriptome wide manner allowing unbiased discoveries. These studies will be complemented with screens in Drosophila melanogaster using an established eye cancer model, previously also successfully used for the studies of T-ALL oncogenes. This study will contribute to our understanding of the pathogenesis of T-ALL and may identify new targets for therapy of this leukemia. In addition, our study will provide a better understanding of how RNA processing is implicated in cancer development in general.

Keywords: leukemia,oncogenes and tumor suppressor genes,rna decay,next-generation sequencing,mouse models
Reactive control protocols for cyber-physical systems (CONTROL-CPS)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Life-long training and career development
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2013-CIG, 2013)
Start date: 2013-09-01
End date: 2017-08-31
Duration (months): 48.0
Total project cost (EUR): 100000.0
EU funding (EUR): 100000.0
Participants: 1
Project status: CLOSED

Cyber-physical systems (CPS) are physical and engineered systems whose operations are monitored, coordinated, controlled, and integrated by a computing and communication core. Systems of this type feature tight interactions between the system's computational and physical components and have attracted increasing attention and investment in both the USA and Europe, for its potential impact on a wide variety of industrial sectors, including aerospace, automotive, chemical production, civil infrastructure, energy, healthcare, manufacturing, materials, and transportation. While most targeted applications of cyber-physical systems are evidently of safety-critical nature, e.g., next generation transportation systems, power grid, and medical devices, how to affordably build and efficiently certify these systems as safe, reliable, and high performance remains one of the grand challenges of CPS research. The proposed research, which lies at the interface of control engineering, computer science, and applied mathematics, aims to bring together a variety of analytical, computational, and experimental tools to address the design and certification challenges in cyber-physical systems. More specifically, it seeks to (1) develop a hybrid systems based modelling framework for networked cyber-physical systems, (2) formally synthesize correct, robust, reactive control protocols for cyber-physical systems from high-level, rigorous specifications that are pertinent to the safe, reliable, and more autonomous operation of cyber-physical systems, and (3) validate and demonstrate the correct-by-construction methodology with numerical simulations and experiments using autonomous mobile robots. Hybrid systems, formal methods, and robotics are three of the key fields the proposed research will directly contribute to. It is expected that the research outcomes will advance the fundamental understanding of and provide new design paradigms for controlling cyber-physical systems.

Keywords: cyber-physical systems,hybrid systems,formal methods,correct-by-construction design,safety-critical systems,nonlinear dynamics,control
Genius before Romanticism: Ingenuity in Early Modern Art and Science (GBR)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Cultures and Cultural Production
Countries involved: United Kingdom
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-07-01
End date: 2019-06-30
Duration (months): 60.0
Total project cost (EUR): 1785670.59
EU funding (EUR): 1785670.59
Participants: 1
Project status: CLOSED

Genius before Romanticism: Ingenuity in Early Modern Art and Science What existed in the European imagination before the Romantic concept of ‘genius’? This five-year project will examine notions of unique talent, heightened imagination and extraordinary creativity in art and science by exploring the language, theories, practices and products of ingenium (ingenuity) ca. 1450-ca. 1750. Drawing on the perspectives of history of art, history of science, technology and medicine, intellectual history and literary studies, the project seeks to capture ingenuity across and between disciplines. Studying five countries (France, Germany, the Netherlands, Italy, Spain and England) across three centuries, it will trace ingenuity’s shifting patterns and fragmented fortunes over the longue durée. Research will be conducted in four strands, focused on distinctive but interrelated aspects of ingenuity. Strand 1, The ‘Language of Ingenuity’, will chart the word history of the ingenuity family of terms. Strand 2, ‘Conceptualizing Ingenuity’, will explore the intellectual framework of ingenuity through its theoretical treatment in natural philosophy and artistic theory. Strand 3, ‘Ingenuity in the Making’, will examine the cunning knowledge of ingenious craftsmen and the properties of ‘spirited’ materials. Strand 4, ‘Ingenious Images’, will investigate the visual culture of ingenuity, from the iconography of ingenium to the witty disingenuousness of optical games. The findings of the project team will be disseminated to a scholarly audience and the wider public through monographs, volumes of essays, a critical edition, an exhibition, conferences and colloquia, and a project website.

Keywords: genius,ingenuity,imagination,inspiration,creativity,wit,melancholy,soul,spirit,mind,renaissance,iconography,visual culture,material culture,art,artists,manuscripts,language
Uncovering the molecular and cellular mechanism of tumor dormancy for the rational design of theranostic nanomedicines (POLYDORM)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic Tools, Therapies and Public Health
Countries involved: Israel
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-04-01
End date: 2019-03-31
Duration (months): 60.0
Total project cost (EUR): 2255920.0
EU funding (EUR): 2255920.0
Participants: 1
Project status: CLOSED

Tumor progression is dependent on a number of sequential steps, including initial tumor-vascular interactions and recruitment of blood vessels, as well as an established interaction of tumor cells with their surrounding microenvironment. Failure of a microscopic tumor, either primary, recurrent or metastatic, to complete one or more of these early stages may lead to delayed clinical manifestation of the cancer and a state of stable non-progressing disease. Micrometastasis, dormant tumors, and residual tumor cells contribute to the occurrence of relapse, and constitute fundamental clinical manifestations of tumor dormancy that together are responsible for the vast majority of cancer deaths. However, although the tumor dormancy phenomenon has critical implications for early detection and treatment of cancer, its biology and genetic characteristics are poorly understood. We now propose to investigate the molecular and cellular changes in tumor-host interactions that govern tumor dormancy, which may lead to the discovery of novel tumor dormancy targets and provide tools for dormancy-dependent tumor therapy strategies. In order to achieve this goal, we will integrate the following basic and translational approaches: (i) Establishment of mouse models of dormant and fast-growing tumor pairs; (ii) Functional and molecular characterization of dormant versus fast-growing tumors, (iii) Design of dormancy-promoting tailor-made polymer therapeutics delivering a combination of microRNAs with chemotherapies; (iv) Polymer conjugation to a prodrug designed to be activated by specific enzymes overexpressed in tumors, Turning-ON a near infra-red (NIR) fluorescence signal. When completed, this proposal will shed light on this fundamental cancer biology phenomenon. A better understanding of tumor dormancy and the availability of markers and therapeutic targets will most likely change our perception of tumor progression and, consequently, the way we diagnose and treat the disease.

Keywords: cancer,angiogenesis,polymer therapeutics,nanomedicine,tumor dormancy,micorrna,theranostics
Race Matter: On the Absent Presence of Race in Forensic Identification (RACEFACEID)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Institutions, Values, Beliefs and behaviour
Countries involved: Netherlands
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-09-01
End date: 2019-08-31
Duration (months): 60.0
Total project cost (EUR): 1999935.0
EU funding (EUR): 1999935.0
Participants: 1
Project status: CLOSED

This ethnographic project on race in forensic practice aims to study how technologies of identification shape race. The focus is on ‘face-making’ in forensic identification; i.e. the reconstruction of faces of unknown persons, a practice entwined with ‘race-making’. In five subprojects the study investigates: How technologies of facial identification in and outside laboratories enact race (subprojects 1-3); How versions of race change as knowledge moves across sites (subproject 4); The mechanism through which race becomes an absent present object, i.e. an object that appears to the surface, e.g. in discourse, to then go underground to hide in the routines and technologies of science, e.g. in genetic markers (subproject 5). The overall objective of this interdisciplinary project is to develop theoretical concepts and methods to grasp the absent present object race. The project goes beyond the social constructivist paradigm, by taking the biological into account. It attends to the materiality of race, i.e. the ways race is shaped as a set of relations between the biological, the social and the technical. This project is innovative in several ways. It is the first to comprehensively study race and forensics, a highly relevant field where knowledge circulates constantly between science and society. The ethnographic subprojects are innovative in the way they compare frontier science of genetics to every day practices, such as facial composite drawings and skull-based reconstructions. Because of its focus on race-in-practice, this project will make a major contribution to the social sciences by providing tools to theorize the materiality of race. Finally, this innovative project comprises a multi-sited ethnography that follows routes of knowledge into and out of the laboratory to various sites in society.

Keywords: anthropology of race and science,forensic anthropology
Pushing Myc inhibition towards the clinic (MYCINHIBINCLINIC)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic Tools, Therapies and Public Health
Countries involved: Spain
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-05-01
End date: 2019-07-31
Duration (months): 63.0
Total project cost (EUR): 1730700.0
EU funding (EUR): 1730700.0
Participants: 1
Project status: CLOSED

Deregulation of the Myc oncogene promotes tumorigenesis in most if not all cancers and is often associated with poor prognosis. However, targeting Myc has long been considered impossible because of potential catastrophic side effects in normal tissues. Despite this general assumption, we showed that Myc inhibition displays extraordinary therapeutic benefit in various transgenic mouse models of cancer, and caused only mild, well-tolerated and reversible side effects in normal tissues. For these studies we have employed a dominant negative of Myc, called Omomyc, which we designed and validated, and that is able to inhibit Myc transactivation function both in vitro and in vivo. Omomyc has so far been utilized exclusively as gene therapy and served the purpose of pre-clinically validating the therapeutic impact of systemic Myc inhibition. In this proposal we intend to push such a therapeutic approach further towards the clinic, making use of 1. Omomyc-based Cell Penetrating Peptides (CPPs): a novel, state-of-the-art potential method for directly utilising Omomyc itself (or a similar peptide) as a drug; 2. A new generation of Myc inhibitory small molecules generated by our collaborators at the Roswell Park Cancer Center. Our study in different mouse models of cancer will provide a comprehensive preclinical validation of such innovative therapies and will potentially boost our therapeutic arsenal against the majority of human cancers

Keywords: mouse models,cell penetrating peptide (cpp),small molecules,lung cancer,glioma
CHROMATIN-REPAIR-CODE: Hacking the chromatin code for DNA repair (CHROMATINREPAIRCODE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Genetics, Genomics, Bioinformatics and Systems Biology
Countries involved: Netherlands
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-03-01
End date: 2019-02-28
Duration (months): 60.0
Total project cost (EUR): 1999575.0
EU funding (EUR): 1999575.0
Participants: 1
Project status: CLOSED

Our cells receive tens of thousands of different DNA lesions per day. Failure to repair these lesions will lead to cell death, mutations and genome instability, which contribute to human diseases such as neurodegenerative disorders and cancer. Efficient recognition and repair of DNA damage, however, is complicated by the fact that genomic DNA is packaged, through histone and non-histone proteins, into a condensed structure called chromatin. The DNA repair machinery has to circumvent this barrier to gain access to the damaged DNA and repair the lesions. Our recent work suggests that chromatin-modifying enzymes (CME) help to overcome this barrier at sites of DNA damage. However, the identity of these CME, their mode of action and interconnections with DNA repair pathways remain largely enigmatic. The aim of this project is to systematically identify and characterize the CME that operate during DNA repair processes in both yeast and human cells. To reach this goal we will use a cross-disciplinary approach that combines novel and cutting-edge genomics approaches with bioinformatics, genetics, biochemistry and high-resolution microscopy. Epigenetics-IDentifier (Epi-ID) will be used as a tool to unveil novel CME, whereas RNAi-interference and genetic interaction mapping studies will pinpoint the CME that may potentially regulate repair of DNA damage. A series of functional assays will eventually characterize their role in distinct DNA repair pathways, focusing on those that counteract DNA strand breaks and replication stress. Together these studies will provide insight into how CME assist cells to repair DNA damage in chromatin and inform on the relevance of CME to maintain genome stability and counteract human diseases.

Keywords: dna damage repair,dna damage tolerance,replication stress,chromatin,rnai screens,genetic interaction mapping,human disease
Positioning the nucleus for cell migration and muscle fiber function (PHONICS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Consolidator grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Portugal
Call:  (ERC-2013-CoG, 2013)
Start date: 2014-07-01
End date: 2019-06-30
Duration (months): 60.0
Total project cost (EUR): 1968000.0
EU funding (EUR): 1968000.0
Participants: 1
Project status: CLOSED

The cell nucleus is positioned at specific places within the cytoplasm and this position is important for different cellular, developmental and physiological processes. Nuclear positioning depends on connections between nuclear envelope proteins and the cytoskeleton. In migrating cells, we found that the nucleus is positioned away from the front of the cell and this event is important for cell migration. We performed an RNAi screen for nuclear positioning and found new nuclear envelope proteins involved in nuclear positioning. In fully developed myofibers, nuclei are specifically positioned at the periphery of the myofiber, while during development and regeneration, as well as in multiple muscle pathologies, the nucleus is centrally positioned. We found new mechanisms drive nuclear movement during myofiber formation. We also showed that nuclear position is important for muscle function. However why nuclear positioning is important for myofiber activity remains an open question. We now propose to use unique systems to monitor cell migration and myofiber formation in combination with biochemistry, cell biology, high- and super-resolution microscopy approaches to: 1) Identify novel molecular mechanisms that mediate nuclear positioning during cell migration and myofiber formation. 3) Determine a role for nuclear positioning in myofiber function as well as the significance of altered nuclear positioning in different forms of muscle pathology. The proposed work will establish new mechanisms for nuclear positioning. Importantly, by identifying mechanisms and understanding the role of nuclear positioning in myofiber function, we will lay the foundations for future studies to ameliorate or treat muscle disorders as well as other conditions where nucleus positioning may prove to play a role such as cancer.