Project acronym ANXIETY & COGNITION
Project How anxiety transforms human cognition: an Affective Neuroscience perspective
Researcher (PI) Gilles Roger Charles Pourtois
Host Institution (HI) UNIVERSITEIT GENT
Call Details Starting Grant (StG), SH3, ERC-2007-StG
Summary Anxiety, a state of apprehension or fear, may provoke cognitive or behavioural disorders and eventually lead to serious medical illnesses. The high prevalence of anxiety disorders in our society sharply contrasts with the lack of clear factual knowledge about the corresponding brain mechanisms at the origin of this profound change in the appraisal of the environment. Little is known about how the psychopathological state of anxiety ultimately turns to a medical condition. The core of this proposal is to gain insight in the neural underpinnings of anxiety and disorders related to anxiety using modern human brain-imaging such as scalp EEG and fMRI. I propose to enlighten how anxiety transforms and shapes human cognition and what the neural correlates and time-course of this modulatory effect are. The primary innovation of this project is the systematic use scalp EEG and fMRI in human participants to better understand the neural mechanisms by which anxiety profoundly influences specific cognitive functions, in particular selective attention and decision-making. The goal of this proposal is to precisely determine the exact timing (using scalp EEG), location, size and extent (using fMRI) of anxiety-related modulations on selective attention and decision-making in the human brain. Here I propose to focus on these two specific processes, because they are likely to reveal selective effects of anxiety on human cognition and can thus serve as powerful models to better figure out how anxiety operates in the human brain. Another important aspect of this project is the fact I envision to help bridge the gap in Health Psychology between fundamental research and clinical practice by proposing alternative revalidation strategies for human adult subjects affected by anxiety-related disorders, which could directly exploit the neuro-scientific discoveries generated in this scientific project.
Summary
Anxiety, a state of apprehension or fear, may provoke cognitive or behavioural disorders and eventually lead to serious medical illnesses. The high prevalence of anxiety disorders in our society sharply contrasts with the lack of clear factual knowledge about the corresponding brain mechanisms at the origin of this profound change in the appraisal of the environment. Little is known about how the psychopathological state of anxiety ultimately turns to a medical condition. The core of this proposal is to gain insight in the neural underpinnings of anxiety and disorders related to anxiety using modern human brain-imaging such as scalp EEG and fMRI. I propose to enlighten how anxiety transforms and shapes human cognition and what the neural correlates and time-course of this modulatory effect are. The primary innovation of this project is the systematic use scalp EEG and fMRI in human participants to better understand the neural mechanisms by which anxiety profoundly influences specific cognitive functions, in particular selective attention and decision-making. The goal of this proposal is to precisely determine the exact timing (using scalp EEG), location, size and extent (using fMRI) of anxiety-related modulations on selective attention and decision-making in the human brain. Here I propose to focus on these two specific processes, because they are likely to reveal selective effects of anxiety on human cognition and can thus serve as powerful models to better figure out how anxiety operates in the human brain. Another important aspect of this project is the fact I envision to help bridge the gap in Health Psychology between fundamental research and clinical practice by proposing alternative revalidation strategies for human adult subjects affected by anxiety-related disorders, which could directly exploit the neuro-scientific discoveries generated in this scientific project.
Max ERC Funding
812 986 €
Duration
Start date: 2008-11-01, End date: 2013-10-31
Project acronym APOLs
Project Role of Apolipoproteins L in immunity and disease
Researcher (PI) Etienne Pays
Host Institution (HI) UNIVERSITE LIBRE DE BRUXELLES
Call Details Advanced Grant (AdG), LS6, ERC-2014-ADG
Summary Work conducted in my laboratory on the trypanosome killing factor of human serum led to the identification
of the primate-specific Apolipoprotein L1 (APOL1) as a novel pore-forming protein with striking similarities
with proteins of the apoptotic BCL2 family. APOL1 belongs to a family of proteins induced under
inflammatory conditions in myeloid and endothelial cells. APOL1 is efficiently neutralized by the SRA
protein of Trypanosoma rhodesiense, accounting for the ability of this trypanosome subspecies to infect
humans and cause sleeping sickness. We found that natural APOL1 variants escaping SRA neutralization and
therefore conferring human resistance to T. rhodesiense are associated with chronic kidney disease.
Moreover, transgenic mice expressing these APOL1 variants exhibit an obese phenotype. Our unpublished
results also indicate that APOLs control the lifespan of dendritic cells and podocytes activated by viral
stimuli. Therefore, we propose that the pathology of APOL variants is due to their deregulated activity on the
control of the cellular lifespan in myeloid/endothelial cells activated by pathogen detection.
This project aims at characterizing (i) the molecular mechanism by which APOLs control the lifespan of
activated dendritic cells and podocytes, which has direct impact on innate immunity and inflammation, and
(ii) the mechanism by which APOL1 variants cause pathology. In addition, we plan to detail the
physiological function of APOLs by studying the phenotype of transgenic mice either expressing human
APOL1 (wild-type and variants) or devoid of APOL genes, which we have recently generated. Finally, we
propose to exploit the extraordinary potential of trypanosomes for antigenic variation in order to produce
SRA variants able to neutralize the pathogenic APOL1 variants. Preliminary experiments suggest that in
podocytes SRA antagonizes APOL1 induction by viral stimulus and subsequent cell death, opening new
perspectives to treat kidney disease.
Summary
Work conducted in my laboratory on the trypanosome killing factor of human serum led to the identification
of the primate-specific Apolipoprotein L1 (APOL1) as a novel pore-forming protein with striking similarities
with proteins of the apoptotic BCL2 family. APOL1 belongs to a family of proteins induced under
inflammatory conditions in myeloid and endothelial cells. APOL1 is efficiently neutralized by the SRA
protein of Trypanosoma rhodesiense, accounting for the ability of this trypanosome subspecies to infect
humans and cause sleeping sickness. We found that natural APOL1 variants escaping SRA neutralization and
therefore conferring human resistance to T. rhodesiense are associated with chronic kidney disease.
Moreover, transgenic mice expressing these APOL1 variants exhibit an obese phenotype. Our unpublished
results also indicate that APOLs control the lifespan of dendritic cells and podocytes activated by viral
stimuli. Therefore, we propose that the pathology of APOL variants is due to their deregulated activity on the
control of the cellular lifespan in myeloid/endothelial cells activated by pathogen detection.
This project aims at characterizing (i) the molecular mechanism by which APOLs control the lifespan of
activated dendritic cells and podocytes, which has direct impact on innate immunity and inflammation, and
(ii) the mechanism by which APOL1 variants cause pathology. In addition, we plan to detail the
physiological function of APOLs by studying the phenotype of transgenic mice either expressing human
APOL1 (wild-type and variants) or devoid of APOL genes, which we have recently generated. Finally, we
propose to exploit the extraordinary potential of trypanosomes for antigenic variation in order to produce
SRA variants able to neutralize the pathogenic APOL1 variants. Preliminary experiments suggest that in
podocytes SRA antagonizes APOL1 induction by viral stimulus and subsequent cell death, opening new
perspectives to treat kidney disease.
Max ERC Funding
2 250 000 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym ARCHGLASS
Project Archaeometry and Archaeology of Ancient Glass Production as a Source for Ancient Technology and Trade of Raw Materials
Researcher (PI) Patrick Degryse
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Starting Grant (StG), SH6, ERC-2009-StG
Summary In this project, innovative techniques to reconstruct ancient economies are developed and new insights in the trade and processing of mineral raw materials are gained based on interdisciplinary archaeological and archaeometrical research. An innovative methodology for and a practical provenance database of the primary origin of natron glass from the Hellenistic-Roman world will be established. The project investigates both production and consumer sites of glass raw materials using both typo-chronological and archaeometrical (isotope geochemical) study of finished glass artefacts at consumer sites as well as mineralogical and chemical characterisation of raw glass and mineral resources at primary production sites. Suitable sand resources in the locations described by ancient authors will be identified through geological prospecting on the basis of literature review and field work. Sand and flux (natron) deposits will be mineralogically and geochemically characterised and compared to the results of the archaeological and geochemical investigations of the glass. Through integrated typo-chronological and archaeometrical analysis, the possible occurrence of primary production centres of raw glass outside the known locations in Syro-Palestine and Egypt, particularly in North-Africa, Italy, Spain and Gaul will be critically studied. In this way, historical, archaeological and archaeometrical data are combined, developing new interdisciplinary techniques for innovative archaeological interpretation of glass trade in the Hellenistic-Roman world.
Summary
In this project, innovative techniques to reconstruct ancient economies are developed and new insights in the trade and processing of mineral raw materials are gained based on interdisciplinary archaeological and archaeometrical research. An innovative methodology for and a practical provenance database of the primary origin of natron glass from the Hellenistic-Roman world will be established. The project investigates both production and consumer sites of glass raw materials using both typo-chronological and archaeometrical (isotope geochemical) study of finished glass artefacts at consumer sites as well as mineralogical and chemical characterisation of raw glass and mineral resources at primary production sites. Suitable sand resources in the locations described by ancient authors will be identified through geological prospecting on the basis of literature review and field work. Sand and flux (natron) deposits will be mineralogically and geochemically characterised and compared to the results of the archaeological and geochemical investigations of the glass. Through integrated typo-chronological and archaeometrical analysis, the possible occurrence of primary production centres of raw glass outside the known locations in Syro-Palestine and Egypt, particularly in North-Africa, Italy, Spain and Gaul will be critically studied. In this way, historical, archaeological and archaeometrical data are combined, developing new interdisciplinary techniques for innovative archaeological interpretation of glass trade in the Hellenistic-Roman world.
Max ERC Funding
954 960 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym ARISTOTLE
Project Aristotle in the Italian Vernacular: Rethinking Renaissance and Early-Modern Intellectual History (c. 1400–c. 1650)
Researcher (PI) Marco Sgarbi
Host Institution (HI) UNIVERSITA CA' FOSCARI VENEZIA
Call Details Starting Grant (StG), SH5, ERC-2013-StG
Summary From the twelfth to the seventeenth century, Aristotle’s writings lay at the foundation of Western culture, providing a body of knowledge and a set of analytical tools applicable to all areas of human investigation. Scholars of the Renaissance have emphasized the remarkable longevity and versatility of Aristotelianism, but their attention has remained firmly, and almost exclusively, fixed on the transmission of Aristotle’s works in Latin. Scarce attention has gone to works in the vernacular. Nonetheless, several important Renaissance figures wished to make Aristotle’s works accessible and available outside the narrow circle of professional philosophers and university professors. They believed that his works could provide essential knowledge to a broad set of readers, and embarked on an intense programme of translation and commentary to see this happen. It is the argument of this project that vernacular Aristotelianism made fundamental contributions to the thought of the period, anticipating many of the features of early modern philosophy and contributing to a new encyclopaedia of knowledge. Our project aims to offer the first detailed and comprehensive study of the vernacular diffusion of Aristotle through a series of analyses of its main texts. We will thus study works that fall within the two main Renaissance divisions of speculative philosophy (metaphysics, natural philosophy, mathematics, and logic) and civil philosophy (ethics, politics, rhetoric, and poetics). We will give strong attention to the contextualization of the texts they examine, as is standard practice in the best kind of intellectual history, focusing on institutional contexts, reading publics, the value of the vernacular, new visions of knowledge and eclecticism. With the work of the PI, two professors, 5 post-docs and two PhD students we aim to make considerable advances in the understanding of both speculative and civil philosophy within vernacular Aristotelianism.
Summary
From the twelfth to the seventeenth century, Aristotle’s writings lay at the foundation of Western culture, providing a body of knowledge and a set of analytical tools applicable to all areas of human investigation. Scholars of the Renaissance have emphasized the remarkable longevity and versatility of Aristotelianism, but their attention has remained firmly, and almost exclusively, fixed on the transmission of Aristotle’s works in Latin. Scarce attention has gone to works in the vernacular. Nonetheless, several important Renaissance figures wished to make Aristotle’s works accessible and available outside the narrow circle of professional philosophers and university professors. They believed that his works could provide essential knowledge to a broad set of readers, and embarked on an intense programme of translation and commentary to see this happen. It is the argument of this project that vernacular Aristotelianism made fundamental contributions to the thought of the period, anticipating many of the features of early modern philosophy and contributing to a new encyclopaedia of knowledge. Our project aims to offer the first detailed and comprehensive study of the vernacular diffusion of Aristotle through a series of analyses of its main texts. We will thus study works that fall within the two main Renaissance divisions of speculative philosophy (metaphysics, natural philosophy, mathematics, and logic) and civil philosophy (ethics, politics, rhetoric, and poetics). We will give strong attention to the contextualization of the texts they examine, as is standard practice in the best kind of intellectual history, focusing on institutional contexts, reading publics, the value of the vernacular, new visions of knowledge and eclecticism. With the work of the PI, two professors, 5 post-docs and two PhD students we aim to make considerable advances in the understanding of both speculative and civil philosophy within vernacular Aristotelianism.
Max ERC Funding
1 483 180 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym AROMA-CFD
Project Advanced Reduced Order Methods with Applications in Computational Fluid Dynamics
Researcher (PI) Gianluigi Rozza
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Call Details Consolidator Grant (CoG), PE1, ERC-2015-CoG
Summary The aim of AROMA-CFD is to create a team of scientists at SISSA for the development of Advanced Reduced Order Modelling techniques with a focus in Computational Fluid Dynamics (CFD), in order to face and overcome many current limitations of the state of the art and improve the capabilities of reduced order methodologies for more demanding applications in industrial, medical and applied sciences contexts. AROMA-CFD deals with strong methodological developments in numerical analysis, with a special emphasis on mathematical modelling and extensive exploitation of computational science and engineering. Several tasks have been identified to tackle important problems and open questions in reduced order modelling: study of bifurcations and instabilities in flows, increasing Reynolds number and guaranteeing stability, moving towards turbulent flows, considering complex geometrical parametrizations of shapes as computational domains into extended networks. A reduced computational and geometrical framework will be developed for nonlinear inverse problems, focusing on optimal flow control, shape optimization and uncertainty quantification. Further, all the advanced developments in reduced order modelling for CFD will be delivered for applications in multiphysics, such as fluid-structure interaction problems and general coupled phenomena involving inviscid, viscous and thermal flows, solids and porous media. The advanced developed framework within AROMA-CFD will provide attractive capabilities for several industrial and medical applications (e.g. aeronautical, mechanical, naval, off-shore, wind, sport, biomedical engineering, and cardiovascular surgery as well), combining high performance computing (in dedicated supercomputing centers) and advanced reduced order modelling (in common devices) to guarantee real time computing and visualization. A new open source software library for AROMA-CFD will be created: ITHACA, In real Time Highly Advanced Computational Applications.
Summary
The aim of AROMA-CFD is to create a team of scientists at SISSA for the development of Advanced Reduced Order Modelling techniques with a focus in Computational Fluid Dynamics (CFD), in order to face and overcome many current limitations of the state of the art and improve the capabilities of reduced order methodologies for more demanding applications in industrial, medical and applied sciences contexts. AROMA-CFD deals with strong methodological developments in numerical analysis, with a special emphasis on mathematical modelling and extensive exploitation of computational science and engineering. Several tasks have been identified to tackle important problems and open questions in reduced order modelling: study of bifurcations and instabilities in flows, increasing Reynolds number and guaranteeing stability, moving towards turbulent flows, considering complex geometrical parametrizations of shapes as computational domains into extended networks. A reduced computational and geometrical framework will be developed for nonlinear inverse problems, focusing on optimal flow control, shape optimization and uncertainty quantification. Further, all the advanced developments in reduced order modelling for CFD will be delivered for applications in multiphysics, such as fluid-structure interaction problems and general coupled phenomena involving inviscid, viscous and thermal flows, solids and porous media. The advanced developed framework within AROMA-CFD will provide attractive capabilities for several industrial and medical applications (e.g. aeronautical, mechanical, naval, off-shore, wind, sport, biomedical engineering, and cardiovascular surgery as well), combining high performance computing (in dedicated supercomputing centers) and advanced reduced order modelling (in common devices) to guarantee real time computing and visualization. A new open source software library for AROMA-CFD will be created: ITHACA, In real Time Highly Advanced Computational Applications.
Max ERC Funding
1 656 579 €
Duration
Start date: 2016-05-01, End date: 2021-04-30
Project acronym ARS
Project Autonomous Robotic Surgery
Researcher (PI) Paolo FIORINI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI VERONA
Call Details Advanced Grant (AdG), PE7, ERC-2016-ADG
Summary The goal of the ARS project is the derivation of a unified framework for the autonomous execution of robotic tasks in challenging environments in which accurate performance and safety are of paramount importance. We have chosen surgery as the research scenario because of its importance, its intrinsic challenges, and the presence of three factors that make this project feasible and timely. In fact, we have recently concluded the I-SUR project demonstrating the feasibility of autonomous surgical actions, we have access to the first big data made available to researchers of clinical robotic surgeries, and we will be able to demonstrate the project results on the high performance surgical robot “da Vinci Research Kit”. The impact of autonomous robots on the workforce is a current subject of discussion, but surgical autonomy will be welcome by the medical personnel, e.g. to carry out simple intervention steps, react faster to unexpected events, or monitor the insurgence of fatigue. The framework for autonomous robotic surgery will include five main research objectives. The first will address the analysis of robotic surgery data set to extract action and knowledge models of the intervention. The second objective will focus on planning, which will consist of instantiating the intervention models to a patient specific anatomy. The third objective will address the design of the hybrid controllers for the discrete and continuous parts of the intervention. The fourth research objective will focus on real time reasoning to assess the intervention state and the overall surgical situation. Finally, the last research objective will address the verification, validation and benchmark of the autonomous surgical robotic capabilities. The research results to be achieved by ARS will contribute to paving the way towards enhancing autonomy and operational capabilities of service robots, with the ambitious goal of bridging the gap between robotic and human task execution capability.
Summary
The goal of the ARS project is the derivation of a unified framework for the autonomous execution of robotic tasks in challenging environments in which accurate performance and safety are of paramount importance. We have chosen surgery as the research scenario because of its importance, its intrinsic challenges, and the presence of three factors that make this project feasible and timely. In fact, we have recently concluded the I-SUR project demonstrating the feasibility of autonomous surgical actions, we have access to the first big data made available to researchers of clinical robotic surgeries, and we will be able to demonstrate the project results on the high performance surgical robot “da Vinci Research Kit”. The impact of autonomous robots on the workforce is a current subject of discussion, but surgical autonomy will be welcome by the medical personnel, e.g. to carry out simple intervention steps, react faster to unexpected events, or monitor the insurgence of fatigue. The framework for autonomous robotic surgery will include five main research objectives. The first will address the analysis of robotic surgery data set to extract action and knowledge models of the intervention. The second objective will focus on planning, which will consist of instantiating the intervention models to a patient specific anatomy. The third objective will address the design of the hybrid controllers for the discrete and continuous parts of the intervention. The fourth research objective will focus on real time reasoning to assess the intervention state and the overall surgical situation. Finally, the last research objective will address the verification, validation and benchmark of the autonomous surgical robotic capabilities. The research results to be achieved by ARS will contribute to paving the way towards enhancing autonomy and operational capabilities of service robots, with the ambitious goal of bridging the gap between robotic and human task execution capability.
Max ERC Funding
2 750 000 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym ArsNova
Project European Ars Nova: Multilingual Poetry and Polyphonic Song in the Late Middle Ages
Researcher (PI) Maria Sofia LANNUTTI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI FIRENZE
Call Details Advanced Grant (AdG), SH5, ERC-2017-ADG
Summary Dante Alighieri at the dawn of the 1300s, as well as Eustache Deschamps almost a century later, conceived poetry as music in itself. But what happens with poetry when it is involved in the complex architecture of polyphony? The aim of this project is to study for the first time the corpus of 14th- and early 15th-century poetry set to music by Ars Nova polyphonists (more than 1200 texts). This repertoire gathers different poetic and musical traditions, as shown by the multilingual anthologies copied during the last years of the Schism. The choice of this corpus is motivated by two primary goals: a) to offer a new interpretation of its meaning and function in the cultural and historical context, one that may be then applied to the rest of coeval European lyric poetry; b) to overcome current disciplinary divisions in order to generate a new methodological balance between the project’s two main fields of interest (Comparative Literature / Musicology). Most Ars Nova polyphonists were directly associated with religious institutions. In many texts, the language of courtly love expresses the values of caritas, the theological virtue that guides wise rulers and leads them to desire the common good. Thus, the poetic figure of the lover becomes a metaphor for the political man, and love poetry can be used as a device for diplomacy, as well as for personal and institutional propaganda. From this unprecedented point of view, the project will develop three research lines in response to the following questions: 1) How is the relationship between poetry and music, and how is the dialogue between the different poetic and musical traditions viewed in relation to each context of production? 2) To what extent does Ars Nova poetry take part in the ‘soft power’ strategies exercised by the entire European political class of the time? 3) Is there a connection between the multilingualism of the manuscript tradition and the perception of the Ars Nova as a European, intercultural repertoire?
Summary
Dante Alighieri at the dawn of the 1300s, as well as Eustache Deschamps almost a century later, conceived poetry as music in itself. But what happens with poetry when it is involved in the complex architecture of polyphony? The aim of this project is to study for the first time the corpus of 14th- and early 15th-century poetry set to music by Ars Nova polyphonists (more than 1200 texts). This repertoire gathers different poetic and musical traditions, as shown by the multilingual anthologies copied during the last years of the Schism. The choice of this corpus is motivated by two primary goals: a) to offer a new interpretation of its meaning and function in the cultural and historical context, one that may be then applied to the rest of coeval European lyric poetry; b) to overcome current disciplinary divisions in order to generate a new methodological balance between the project’s two main fields of interest (Comparative Literature / Musicology). Most Ars Nova polyphonists were directly associated with religious institutions. In many texts, the language of courtly love expresses the values of caritas, the theological virtue that guides wise rulers and leads them to desire the common good. Thus, the poetic figure of the lover becomes a metaphor for the political man, and love poetry can be used as a device for diplomacy, as well as for personal and institutional propaganda. From this unprecedented point of view, the project will develop three research lines in response to the following questions: 1) How is the relationship between poetry and music, and how is the dialogue between the different poetic and musical traditions viewed in relation to each context of production? 2) To what extent does Ars Nova poetry take part in the ‘soft power’ strategies exercised by the entire European political class of the time? 3) Is there a connection between the multilingualism of the manuscript tradition and the perception of the Ars Nova as a European, intercultural repertoire?
Max ERC Funding
2 193 375 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym ART
Project Aberrant RNA degradation in T-cell leukemia
Researcher (PI) Jan Cools
Host Institution (HI) VIB
Call Details Consolidator Grant (CoG), LS4, ERC-2013-CoG
Summary "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."
Summary
"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."
Max ERC Funding
1 998 300 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym ASNODEV
Project Aspirations Social Norms and Development
Researcher (PI) Eliana LA FERRARA
Host Institution (HI) UNIVERSITA COMMERCIALE LUIGI BOCCONI
Call Details Advanced Grant (AdG), SH1, ERC-2015-AdG
Summary Development economists and policymakers often face scenarios in which poor people do not make choices that would help them get out of poverty due to an “aspiration failure”: the poor perceive certain goals as unattainable and do not invest towards those goals, thus perpetuating their own state of poverty. The aim of this proposal is to improve our understanding of the relationship between aspirations and socio-economic outcomes of disadvantaged individuals, in order to answer the question: Can we design policy interventions that shift aspirations in a way that is conducive to development?
In addressing the above question a fundamental role is played by social norms and by the ability of individuals to coordinate on “new” aspirations, hence the analysis of social effects is a salient feature of this proposal.
The proposed research is organized in two workpackages. The first focuses on the media as a vehicle for changing aspirations, examining both commercial TV programs and “educational entertainment”. The second workpackage examines “tailored” interventions designed to address specific determinants of aspiration failures (e.g., psychological support to reduce perceived barriers; inter-racial interaction to change stereotypes; institutional reform to strengthen women’s rights and reduce the gender aspiration gap).
The methodology will involve rigorous evaluation of several interventions directly designed to or indirectly affecting aspirations and social norms. Original data collected through survey work, large administrative datasets and media content analysis will be used.
The results of this project will advance our knowledge on the sources of aspiration failures by poor people and on the interplay between aspirations and social norms, eventually opening the avenue for a new array of anti-poverty policies.
Summary
Development economists and policymakers often face scenarios in which poor people do not make choices that would help them get out of poverty due to an “aspiration failure”: the poor perceive certain goals as unattainable and do not invest towards those goals, thus perpetuating their own state of poverty. The aim of this proposal is to improve our understanding of the relationship between aspirations and socio-economic outcomes of disadvantaged individuals, in order to answer the question: Can we design policy interventions that shift aspirations in a way that is conducive to development?
In addressing the above question a fundamental role is played by social norms and by the ability of individuals to coordinate on “new” aspirations, hence the analysis of social effects is a salient feature of this proposal.
The proposed research is organized in two workpackages. The first focuses on the media as a vehicle for changing aspirations, examining both commercial TV programs and “educational entertainment”. The second workpackage examines “tailored” interventions designed to address specific determinants of aspiration failures (e.g., psychological support to reduce perceived barriers; inter-racial interaction to change stereotypes; institutional reform to strengthen women’s rights and reduce the gender aspiration gap).
The methodology will involve rigorous evaluation of several interventions directly designed to or indirectly affecting aspirations and social norms. Original data collected through survey work, large administrative datasets and media content analysis will be used.
The results of this project will advance our knowledge on the sources of aspiration failures by poor people and on the interplay between aspirations and social norms, eventually opening the avenue for a new array of anti-poverty policies.
Max ERC Funding
1 618 125 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym AST
Project Automatic System Testing
Researcher (PI) Leonardo MARIANI
Host Institution (HI) UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Call Details Proof of Concept (PoC), ERC-2018-PoC
Summary Verifying the correctness of software systems requires extensive and expensive testing sessions. While there are tools and methodologies to efficiently address unit and integration testing, system testing is still largely the result of manual effort.
Testing software applications at the system level requires executing the applications through their interfaces to verify the correctness of their functionalities and stimulate all their layers and components. Automating just part of this process can dramatically improve the effectiveness of verification activities and significantly reduce development costs, relevantly alleviating developers from their verification effort.
This project addresses the development of a pre-commercial tool that has the unique capability of efficiently and automatically generating semantically-relevant system test cases equipped with functional oracles. This capability derives from the AUGUSTO technique, which is an outcome of the Learn ERC project. The idea behind Augusto is to exploit the common-sense knowledge, that is, the background knowledge that every computer user has and that normally lets her/him use software applications without the need of accessing any documentation or manual. Once this knowledge is represented abstractly and then embedded in AUGUSTO, the technique can automatically adapt its definition to the software under test every time a program is tested.
This development work will be performed jointly with A company that produces and markets testing tools.
Summary
Verifying the correctness of software systems requires extensive and expensive testing sessions. While there are tools and methodologies to efficiently address unit and integration testing, system testing is still largely the result of manual effort.
Testing software applications at the system level requires executing the applications through their interfaces to verify the correctness of their functionalities and stimulate all their layers and components. Automating just part of this process can dramatically improve the effectiveness of verification activities and significantly reduce development costs, relevantly alleviating developers from their verification effort.
This project addresses the development of a pre-commercial tool that has the unique capability of efficiently and automatically generating semantically-relevant system test cases equipped with functional oracles. This capability derives from the AUGUSTO technique, which is an outcome of the Learn ERC project. The idea behind Augusto is to exploit the common-sense knowledge, that is, the background knowledge that every computer user has and that normally lets her/him use software applications without the need of accessing any documentation or manual. Once this knowledge is represented abstractly and then embedded in AUGUSTO, the technique can automatically adapt its definition to the software under test every time a program is tested.
This development work will be performed jointly with A company that produces and markets testing tools.
Max ERC Funding
150 000 €
Duration
Start date: 2019-01-01, End date: 2020-06-30
