Project acronym CancerFluxome
Project Cancer Cellular Metabolism across Space and Time
Researcher (PI) Tomer Shlomi
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), LS2, ERC-2016-STG
Summary The metabolism of cancer cells is altered to meet cellular requirements for growth, providing novel means to selectively target tumorigenesis. While extensively studied, our current view of cancer cellular metabolism is fundamentally limited by lack of information on variability in metabolic activity between distinct subcellular compartments and cells.
We propose to develop a spatio-temporal fluxomics approach for quantifying metabolic fluxes in the cytoplasm vs. mitochondria as well as their cell-cycle dynamics, combining mass-spectrometry based isotope tracing with cell synchronization, rapid cellular fractionation, and computational metabolic network modelling.
Spatio-temporal fluxomics will be used to revisit and challenge our current understanding of central metabolism and its induced adaptation to oncogenic events – an important endeavour considering that mitochondrial bioenergetics and biosynthesis are required for tumorigenesis and accumulating evidences for metabolic alterations throughout the cell-cycle.
Our preliminary results show intriguing oscillations between oxidative and reductive TCA cycle flux throughout the cell-cycle. We will explore the extent to which cells adapt their metabolism to fulfil the changing energetic and anabolic demands throughout the cell-cycle, how metabolic oscillations are regulated, and their benefit to cells in terms of thermodynamic efficiency. Spatial flux analysis will be instrumental for investigating glutaminolysis - a ‘hallmark’ metabolic adaptation in cancer involving shuttling of metabolic intermediates and cofactors between mitochondria and cytoplasm.
On a clinical front, our spatio-temporal fluxomics analysis will enable to disentangle oncogene-induced flux alterations, having an important tumorigenic role, from artefacts originating from population averaging. A comprehensive view of how cells adapt their metabolism due to oncogenic mutations will reveal novel targets for anti-cancer drugs.
Summary
The metabolism of cancer cells is altered to meet cellular requirements for growth, providing novel means to selectively target tumorigenesis. While extensively studied, our current view of cancer cellular metabolism is fundamentally limited by lack of information on variability in metabolic activity between distinct subcellular compartments and cells.
We propose to develop a spatio-temporal fluxomics approach for quantifying metabolic fluxes in the cytoplasm vs. mitochondria as well as their cell-cycle dynamics, combining mass-spectrometry based isotope tracing with cell synchronization, rapid cellular fractionation, and computational metabolic network modelling.
Spatio-temporal fluxomics will be used to revisit and challenge our current understanding of central metabolism and its induced adaptation to oncogenic events – an important endeavour considering that mitochondrial bioenergetics and biosynthesis are required for tumorigenesis and accumulating evidences for metabolic alterations throughout the cell-cycle.
Our preliminary results show intriguing oscillations between oxidative and reductive TCA cycle flux throughout the cell-cycle. We will explore the extent to which cells adapt their metabolism to fulfil the changing energetic and anabolic demands throughout the cell-cycle, how metabolic oscillations are regulated, and their benefit to cells in terms of thermodynamic efficiency. Spatial flux analysis will be instrumental for investigating glutaminolysis - a ‘hallmark’ metabolic adaptation in cancer involving shuttling of metabolic intermediates and cofactors between mitochondria and cytoplasm.
On a clinical front, our spatio-temporal fluxomics analysis will enable to disentangle oncogene-induced flux alterations, having an important tumorigenic role, from artefacts originating from population averaging. A comprehensive view of how cells adapt their metabolism due to oncogenic mutations will reveal novel targets for anti-cancer drugs.
Max ERC Funding
1 481 250 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
Project acronym CELLREPROGRAMMING
Project Uncovering the Mechanisms of Epigenetic Reprogramming of Pluripotent and Somatic Cell States
Researcher (PI) Yaqub Hanna
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Starting Grant (StG), LS3, ERC-2011-StG_20101109
Summary The generation of animals by nuclear transfer demonstrated that the epigenetic state of somatic cells could be reset to an embryonic state, capable of directing the development of a new organism. The nuclear cloning technology is of interest for transplantation medicine, but any application is hampered by the inefficiency and ethical problems. A breakthrough solving these issues has been the in vitro derivation of reprogrammed Induced Pluripotent Stem “iPS” cells by the ectopic expression of defined transcription factors in somatic cells. iPS cells recapitulate all defining features of embryo-derived pluripotent stem cells, including the ability to differentiate into all somatic cell types. Further, recent publications have demonstrated the ability to directly trans-differentiate somatic cell types by ectopic expression of lineage specification factors. Thus, it is becoming increasingly clear that an ultimate goal in the stem cell field is to enable scientists to have the power to safely manipulate somatic cells by “reprogramming” their behavior at will. However, to frame this challenge, we must understand the basic mechanisms underlying the generation of reprogrammed cells in parallel to designing strategies for their medical application and their use in human disease specific research. In this ERC Starting Grant proposal, I describe comprehensive lines of experimentation that I plan to conduct in my new lab scheduled to open in April 2011 at the Weizmann Institute of Science. We will utilize exacting transgenic mammalian models and high throughput sequencing and genomic screening tools for in depth characterization of the molecular “rules” of rewiring the epigenome of somatic and pluripotent cell states. The proposed research endeavors will not only contribute to the development of safer strategies for cell reprogramming, but will also help decipher how diverse gene expression programs lead to cellular specification during normal development.
Summary
The generation of animals by nuclear transfer demonstrated that the epigenetic state of somatic cells could be reset to an embryonic state, capable of directing the development of a new organism. The nuclear cloning technology is of interest for transplantation medicine, but any application is hampered by the inefficiency and ethical problems. A breakthrough solving these issues has been the in vitro derivation of reprogrammed Induced Pluripotent Stem “iPS” cells by the ectopic expression of defined transcription factors in somatic cells. iPS cells recapitulate all defining features of embryo-derived pluripotent stem cells, including the ability to differentiate into all somatic cell types. Further, recent publications have demonstrated the ability to directly trans-differentiate somatic cell types by ectopic expression of lineage specification factors. Thus, it is becoming increasingly clear that an ultimate goal in the stem cell field is to enable scientists to have the power to safely manipulate somatic cells by “reprogramming” their behavior at will. However, to frame this challenge, we must understand the basic mechanisms underlying the generation of reprogrammed cells in parallel to designing strategies for their medical application and their use in human disease specific research. In this ERC Starting Grant proposal, I describe comprehensive lines of experimentation that I plan to conduct in my new lab scheduled to open in April 2011 at the Weizmann Institute of Science. We will utilize exacting transgenic mammalian models and high throughput sequencing and genomic screening tools for in depth characterization of the molecular “rules” of rewiring the epigenome of somatic and pluripotent cell states. The proposed research endeavors will not only contribute to the development of safer strategies for cell reprogramming, but will also help decipher how diverse gene expression programs lead to cellular specification during normal development.
Max ERC Funding
1 960 000 €
Duration
Start date: 2011-11-01, End date: 2016-10-31
Project acronym ChangeBehavNeuro
Project Novel Mechanism of Behavioural Change
Researcher (PI) Tom SCHONBERG
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Starting Grant (StG), SH4, ERC-2016-STG
Summary Understanding how values of different options that lead to choice are represented in the brain is a basic scientific question with far reaching implications. I recently showed that by the mere-association of a cue and a button press we could influence preferences of snack food items up to two months following a single training session lasting less than an hour. This novel behavioural change manipulation cannot be explained by any of the current learning theories, as external reinforcement was not used in the process, nor was the context of the decision changed. Current choice theories focus on goal directed behaviours where the value of the outcome guides choice, versus habit-based behaviours where an action is repeated up to the point that the value of the outcome no longer guides choice. However, in this novel task training via the involvement of low-level visual, auditory and motor mechanisms influenced high-level choice behaviour. Thus, the far-reaching goal of this project is to study the mechanism, by which low-level sensory, perceptual and motor neural processes underlie value representation and change in the human brain even in the absence of external reinforcement. I will use behavioural, eye-gaze and functional MRI experiments to test how low-level features influence the neural representation of value. I will then test how they interact with the known striatal representation of reinforced behavioural change, which has been the main focus of research thus far. Finally, I will address the basic question of dynamic neural plasticity and if neural signatures during training predict long term success of sustained behavioural change. This research aims at a paradigmatic shift in the field of learning and decision-making, leading to the development of novel interventions with potential societal impact of helping those suffering from health-injuring behaviours such as addictions, eating or mood disorders, all in need of a long lasting behavioural change.
Summary
Understanding how values of different options that lead to choice are represented in the brain is a basic scientific question with far reaching implications. I recently showed that by the mere-association of a cue and a button press we could influence preferences of snack food items up to two months following a single training session lasting less than an hour. This novel behavioural change manipulation cannot be explained by any of the current learning theories, as external reinforcement was not used in the process, nor was the context of the decision changed. Current choice theories focus on goal directed behaviours where the value of the outcome guides choice, versus habit-based behaviours where an action is repeated up to the point that the value of the outcome no longer guides choice. However, in this novel task training via the involvement of low-level visual, auditory and motor mechanisms influenced high-level choice behaviour. Thus, the far-reaching goal of this project is to study the mechanism, by which low-level sensory, perceptual and motor neural processes underlie value representation and change in the human brain even in the absence of external reinforcement. I will use behavioural, eye-gaze and functional MRI experiments to test how low-level features influence the neural representation of value. I will then test how they interact with the known striatal representation of reinforced behavioural change, which has been the main focus of research thus far. Finally, I will address the basic question of dynamic neural plasticity and if neural signatures during training predict long term success of sustained behavioural change. This research aims at a paradigmatic shift in the field of learning and decision-making, leading to the development of novel interventions with potential societal impact of helping those suffering from health-injuring behaviours such as addictions, eating or mood disorders, all in need of a long lasting behavioural change.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym CODEX
Project Decoding Domesticate DNA in Archaeological Bone and Manuscripts
Researcher (PI) Daniel Gerard Bradley
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Call Details Advanced Grant (AdG), SH6, ERC-2011-ADG_20110406
Summary Through animal domestication humans profoundly altered their relationship with nature, controlling the breeding of their major food sources for material, social or symbolic profit. Understanding this complex process is a compelling research aim. There is a need to develop new high-resolution genetic tools to put flesh on the bones of this two-millenium long transition. These will take advantage of very recent advances: targeted next generation DNA sequencing, high throughput screening of expertly provenanced archaeological samples, and emerging knowledge of modern cattle, sheep and goat genome science plus their genetic geographies. Combining these, this proposal will develop an ancient DNA data matrix that will be unparalleled in archaeological science. These data will unlock the key genetic changes that accompany the domestic state and the breeding structures that are a consequence of human management. It will also identify the wild and proto-domestic populations that later herds emerge from. A more precise geography and timing of the key changes will enable richer contextualising inform our assessement of why these changes take place. The 10,000 year matrix for each species will function as a standard spatiotemporal reference grid on which any subsequent bone or animal artefact may be placed i.e. via genetic postcoding. Exceptional discontinuities in the matrix will highlight points of strong historical interest such as the emergence of new trade networks, migrations and periods of economic turbulence - perhaps driven by climate fluctuations or plagues. The final work objectives will focus on diachronic sample assemblages selected to have particular import for both historical events and transitions in material culture. For example, manuscript vellum samples will give a uniquely dated series that will enable correlation of genetic change with historical studies of the timing and impact of past animal plagues (e.g. in C 14th and C 18th Europe).
Summary
Through animal domestication humans profoundly altered their relationship with nature, controlling the breeding of their major food sources for material, social or symbolic profit. Understanding this complex process is a compelling research aim. There is a need to develop new high-resolution genetic tools to put flesh on the bones of this two-millenium long transition. These will take advantage of very recent advances: targeted next generation DNA sequencing, high throughput screening of expertly provenanced archaeological samples, and emerging knowledge of modern cattle, sheep and goat genome science plus their genetic geographies. Combining these, this proposal will develop an ancient DNA data matrix that will be unparalleled in archaeological science. These data will unlock the key genetic changes that accompany the domestic state and the breeding structures that are a consequence of human management. It will also identify the wild and proto-domestic populations that later herds emerge from. A more precise geography and timing of the key changes will enable richer contextualising inform our assessement of why these changes take place. The 10,000 year matrix for each species will function as a standard spatiotemporal reference grid on which any subsequent bone or animal artefact may be placed i.e. via genetic postcoding. Exceptional discontinuities in the matrix will highlight points of strong historical interest such as the emergence of new trade networks, migrations and periods of economic turbulence - perhaps driven by climate fluctuations or plagues. The final work objectives will focus on diachronic sample assemblages selected to have particular import for both historical events and transitions in material culture. For example, manuscript vellum samples will give a uniquely dated series that will enable correlation of genetic change with historical studies of the timing and impact of past animal plagues (e.g. in C 14th and C 18th Europe).
Max ERC Funding
2 499 693 €
Duration
Start date: 2012-07-01, End date: 2018-06-30
Project acronym CrackEpitranscriptom
Project Cracking the epitranscriptome
Researcher (PI) Schraga SCHWARTZ
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Starting Grant (StG), LS2, ERC-2016-STG
Summary Over 100 types of distinct modifications are catalyzed on RNA molecules post-transcriptionally. In an analogous manner to well-studied chemical modifications on proteins or DNA, modifications on RNA - and particularly on mRNA - harbor the exciting potential of regulating the complex and interlinked life cycle of these molecules. The most abundant modification in mammalian and yeast mRNA is N6-methyladenosine (m6A). We have pioneered approaches for mapping m6A in a transcriptome wide manner, and we and others have identified factors involved in encoding and decoding m6A. While experimental disruption of these factors is associated with severe phenotypes, the role of m6A remains enigmatic. No single methylated site has been shown to causally underlie any physiological or molecular function. This proposal aims to establish a framework for systematically deciphering the molecular function of a modification and its underlying mechanisms and to uncover the physiological role of the modification in regulation of a cellular response. We will apply this framework to m6A in the context of meiosis in budding yeast, as m6A dynamically accumulates on meiotic mRNAs and as the methyltransferase catalyzing m6A is essential for meiosis. We will (1) aim to elucidate the physiological targets of methylation governing entry into meiosis (2) seek to elucidate the function of m6A at the molecular level, and understand its impact on the various steps of the mRNA life cycle, (3) seek to understand the mechanisms underlying its effects. These aims will provide a comprehensive framework for understanding how the epitranscriptome, an emerging post-transcriptional layer of regulation, fine-tunes gene regulation and impacts cellular decision making in a dynamic response, and will set the stage towards dissecting the roles of m6A and of an expanding set of mRNA modifications in more complex and disease related systems.
Summary
Over 100 types of distinct modifications are catalyzed on RNA molecules post-transcriptionally. In an analogous manner to well-studied chemical modifications on proteins or DNA, modifications on RNA - and particularly on mRNA - harbor the exciting potential of regulating the complex and interlinked life cycle of these molecules. The most abundant modification in mammalian and yeast mRNA is N6-methyladenosine (m6A). We have pioneered approaches for mapping m6A in a transcriptome wide manner, and we and others have identified factors involved in encoding and decoding m6A. While experimental disruption of these factors is associated with severe phenotypes, the role of m6A remains enigmatic. No single methylated site has been shown to causally underlie any physiological or molecular function. This proposal aims to establish a framework for systematically deciphering the molecular function of a modification and its underlying mechanisms and to uncover the physiological role of the modification in regulation of a cellular response. We will apply this framework to m6A in the context of meiosis in budding yeast, as m6A dynamically accumulates on meiotic mRNAs and as the methyltransferase catalyzing m6A is essential for meiosis. We will (1) aim to elucidate the physiological targets of methylation governing entry into meiosis (2) seek to elucidate the function of m6A at the molecular level, and understand its impact on the various steps of the mRNA life cycle, (3) seek to understand the mechanisms underlying its effects. These aims will provide a comprehensive framework for understanding how the epitranscriptome, an emerging post-transcriptional layer of regulation, fine-tunes gene regulation and impacts cellular decision making in a dynamic response, and will set the stage towards dissecting the roles of m6A and of an expanding set of mRNA modifications in more complex and disease related systems.
Max ERC Funding
1 402 666 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym DIASPORAINTRANSITION
Project A Diaspora in Transition - Cultural and Religious Changes in Western Sephardic Communities in the Early Modern Period
Researcher (PI) Yosef Mauricio Kaplan
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Advanced Grant (AdG), SH6, ERC-2011-ADG_20110406
Summary The communities of the Western Sephardic Diaspora were founded in the 16th and 17th centuries by New Christians from Iberia who returned to Judaism that had been abandoned by their ancestors in the late Middle Ages. This project will concentrate on the changes in the religious conceptions and behavior as well as the cultural patterns of the communities of Amsterdam, Hamburg, Leghorn, London, and Bordeaux. We will analyze the vigorous activity of their leaders to set the boundaries of their new religious identity in comparison to the policy of several Christian “communities of belief,” which went into exile following religious persecution in their homelands. We will also examine the changes in the attitude toward Judaism during the 17th century in certain segments of the Sephardic Diaspora: rather than a normative system covering every area of life, Judaism came to be seen as a system of faith restricted to the religious sphere. We will seek to explain the extent to which this significant change influenced their institutions and social behaviour. This study will provide us with better understanding of the place of the Jews in European society. At the same time, we will subject a central series of concepts in the historiographical discourse of the Early Modern Period to critical analysis: confessionalization, disciplinary revolution, civilizing process, affective individualism, etc. This phase of the research will be based on qualitative and quantitative analysis of many hundreds of documents, texts and the material remains of these communities. Using sociological and anthropological models, we will analyze ceremonies and rituals described at length in the sources, the social and cultural meaning of the architecture of the Sephardic synagogues of that time, and of other visual symbols.
Summary
The communities of the Western Sephardic Diaspora were founded in the 16th and 17th centuries by New Christians from Iberia who returned to Judaism that had been abandoned by their ancestors in the late Middle Ages. This project will concentrate on the changes in the religious conceptions and behavior as well as the cultural patterns of the communities of Amsterdam, Hamburg, Leghorn, London, and Bordeaux. We will analyze the vigorous activity of their leaders to set the boundaries of their new religious identity in comparison to the policy of several Christian “communities of belief,” which went into exile following religious persecution in their homelands. We will also examine the changes in the attitude toward Judaism during the 17th century in certain segments of the Sephardic Diaspora: rather than a normative system covering every area of life, Judaism came to be seen as a system of faith restricted to the religious sphere. We will seek to explain the extent to which this significant change influenced their institutions and social behaviour. This study will provide us with better understanding of the place of the Jews in European society. At the same time, we will subject a central series of concepts in the historiographical discourse of the Early Modern Period to critical analysis: confessionalization, disciplinary revolution, civilizing process, affective individualism, etc. This phase of the research will be based on qualitative and quantitative analysis of many hundreds of documents, texts and the material remains of these communities. Using sociological and anthropological models, we will analyze ceremonies and rituals described at length in the sources, the social and cultural meaning of the architecture of the Sephardic synagogues of that time, and of other visual symbols.
Max ERC Funding
1 671 200 €
Duration
Start date: 2012-03-01, End date: 2018-02-28
Project acronym EMODHEBREW
Project The emergence of Modern Hebrew as a case-study of linguistic discontinuity
Researcher (PI) Edit Doron
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Advanced Grant (AdG), SH4, ERC-2016-ADG
Summary The pioneering enterprise I propose is the study of a particular type of linguistic discontinuity – language revival – inspired by the revival of Hebrew at the end of the 19th century. The historical and sociocultural dimensions the revival have been studied before, but not its linguistic dimensions. My main aim is to construct a model of the linguistic factors which have shaped the revival of Hebrew. I expect this model to provide clues for the understanding of the process of language revival in general. For a language to be revived, a new grammar must be created by its native speakers. I hypothesize that the new grammar is formed by some of the general principles which also govern other better known cases of linguistic discontinuity (creoles, mixed languages, emergent sign languages etc.). The model I will develop will lay the foundation for a new subfield within the study of discontinuity – the study of language revival. I will start with careful work of documenting the development of the grammar of Modern Hebrew, in particular its syntax, something which has not been done systematically before. One product of the project will be a linguistic application for the documentation and annotation of the novel syntactic constructions of Modern Hebrew, their sources in previous stages of Hebrew and in the languages with which Modern Hebrew was in contact at the time of the revival, and the development of these constructions since the beginning of the revival until the present time. The linguistic application will be made available on the web for other linguists to use and to contribute to. The institution of an expanding data-base of the syntactic innovations of Modern Hebrew which comprises both documentation/ annotation and theoretical modeling which could be applied to other languages makes this an extremely ambitious proposal with potentially wide-reaching ramifications for the revival and revitalization of the languages of ethno-linguistic minorities world wide.
Summary
The pioneering enterprise I propose is the study of a particular type of linguistic discontinuity – language revival – inspired by the revival of Hebrew at the end of the 19th century. The historical and sociocultural dimensions the revival have been studied before, but not its linguistic dimensions. My main aim is to construct a model of the linguistic factors which have shaped the revival of Hebrew. I expect this model to provide clues for the understanding of the process of language revival in general. For a language to be revived, a new grammar must be created by its native speakers. I hypothesize that the new grammar is formed by some of the general principles which also govern other better known cases of linguistic discontinuity (creoles, mixed languages, emergent sign languages etc.). The model I will develop will lay the foundation for a new subfield within the study of discontinuity – the study of language revival. I will start with careful work of documenting the development of the grammar of Modern Hebrew, in particular its syntax, something which has not been done systematically before. One product of the project will be a linguistic application for the documentation and annotation of the novel syntactic constructions of Modern Hebrew, their sources in previous stages of Hebrew and in the languages with which Modern Hebrew was in contact at the time of the revival, and the development of these constructions since the beginning of the revival until the present time. The linguistic application will be made available on the web for other linguists to use and to contribute to. The institution of an expanding data-base of the syntactic innovations of Modern Hebrew which comprises both documentation/ annotation and theoretical modeling which could be applied to other languages makes this an extremely ambitious proposal with potentially wide-reaching ramifications for the revival and revitalization of the languages of ethno-linguistic minorities world wide.
Max ERC Funding
2 498 750 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym European Unions
Project Labour Politics and the EU's New Economic Governance Regime
Researcher (PI) Roland ERNE
Host Institution (HI) UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Call Details Consolidator Grant (CoG), SH2, ERC-2016-COG
Summary Trade unions play a major role in democratic interest intermediation. This role is currently threatened by the increasingly authoritarian strain in EU’s new economic governance (NEG). This project aims to explore the challenges and possibilities that the NEG poses to labour politics. Until recently, European labour politics has mainly been shaped by horizontal market integration through the free movement of goods, capital, services and people. After the financial crisis, the latter has been complemented by vertical integration effected through the direct surveillance of member states. The resulting NEG opens contradictory possibilities for labour movements in Europe.
On the one hand, the reliance of the NEG on vertical surveillance makes decisions taken in its name more tangible, offering concrete targets for contentious transnational collective action. On the other hand however, the NEG mimics the governance structures of multinational firms, by using key performance indicators that put countries in competition with one another. This constitutes a deterrent to transnational collective action. The NEG’s interventionist and competitive strains also pose the threat of nationalist counter-movements, thus making European collective action ever more vital for the future of EU integration and democracy.
This project has the following objectives:
1. To understand the interrelation between NEG and existing ‘horizontal’ EU economic governance; and the shifts in labour politics triggered by NEG;
2. To open up novel analytical approaches that are able to capture both national and transnational social processes at work;
3. To analyse the responses of established trade unions and new social movements to NEG in selected subject areas and economic sectors at national and EU levels, and their feedback effects on NEG;
4. To develop a new scientific paradigm capable of accounting for the interplay between EU economic governance, labour politics and EU democracy.
Summary
Trade unions play a major role in democratic interest intermediation. This role is currently threatened by the increasingly authoritarian strain in EU’s new economic governance (NEG). This project aims to explore the challenges and possibilities that the NEG poses to labour politics. Until recently, European labour politics has mainly been shaped by horizontal market integration through the free movement of goods, capital, services and people. After the financial crisis, the latter has been complemented by vertical integration effected through the direct surveillance of member states. The resulting NEG opens contradictory possibilities for labour movements in Europe.
On the one hand, the reliance of the NEG on vertical surveillance makes decisions taken in its name more tangible, offering concrete targets for contentious transnational collective action. On the other hand however, the NEG mimics the governance structures of multinational firms, by using key performance indicators that put countries in competition with one another. This constitutes a deterrent to transnational collective action. The NEG’s interventionist and competitive strains also pose the threat of nationalist counter-movements, thus making European collective action ever more vital for the future of EU integration and democracy.
This project has the following objectives:
1. To understand the interrelation between NEG and existing ‘horizontal’ EU economic governance; and the shifts in labour politics triggered by NEG;
2. To open up novel analytical approaches that are able to capture both national and transnational social processes at work;
3. To analyse the responses of established trade unions and new social movements to NEG in selected subject areas and economic sectors at national and EU levels, and their feedback effects on NEG;
4. To develop a new scientific paradigm capable of accounting for the interplay between EU economic governance, labour politics and EU democracy.
Max ERC Funding
1 997 132 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym EvoDevoQuorum
Project Evolution and Development of Bacterial Communication
Researcher (PI) Avigdor Eldar
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Starting Grant (StG), LS2, ERC-2011-StG_20101109
Summary Bacterial cooperation underlies many bacterial traits of practical interest. Many social traits of bacteria are regulated by inter-cellular signalling pathways, generally known as quorum sensing (QS). QS has been proposed as novel target for anti-virulence treatment. To this aim, there is a need to better understand the mechanisms of QS and their social and evolutionary impact.
While the basic schemes of a single quorum sensing pathway acting in homogenous conditions are well understood, the system’s level function of QS regulatory networks can only be appreciated by considering the role phenotypic and genetic variability has on shaping the network’s structure and function. Phenotypic variability in complex communities may arise from division of labour between cells and environmental gradients and substantially impact the way cells secrete and interpret QS signals. Genetic variability in QS networks may lead to multiple social relations between cells of different genotypes including cross-talks, interception, manipulation and quenching of signals. This will affect the population structure and performance.
The proposed project will study the function of QS signalling in heterogeneous communities. Phenotypic variability and its impact on QS function will be studied in a spatially inhomogeneous cooperating system. Genetic variability will be studied at the macro and micro-scales in a bacterial species showing rapid diversification of their QS networks. Finally, we will rationally design strains with superior ‘cheating’ strategies that can invade and eliminate a cooperative population.
Throughout this project, we will use a combination of experimental techniques from microbiology, socio-biology, genetics and microscopy together with mathematical analysis tools from systems biology, population genetics and game theory, to study bacterial cooperation and its dependence on the underlying communication network, social complexity and environmental variation.
Summary
Bacterial cooperation underlies many bacterial traits of practical interest. Many social traits of bacteria are regulated by inter-cellular signalling pathways, generally known as quorum sensing (QS). QS has been proposed as novel target for anti-virulence treatment. To this aim, there is a need to better understand the mechanisms of QS and their social and evolutionary impact.
While the basic schemes of a single quorum sensing pathway acting in homogenous conditions are well understood, the system’s level function of QS regulatory networks can only be appreciated by considering the role phenotypic and genetic variability has on shaping the network’s structure and function. Phenotypic variability in complex communities may arise from division of labour between cells and environmental gradients and substantially impact the way cells secrete and interpret QS signals. Genetic variability in QS networks may lead to multiple social relations between cells of different genotypes including cross-talks, interception, manipulation and quenching of signals. This will affect the population structure and performance.
The proposed project will study the function of QS signalling in heterogeneous communities. Phenotypic variability and its impact on QS function will be studied in a spatially inhomogeneous cooperating system. Genetic variability will be studied at the macro and micro-scales in a bacterial species showing rapid diversification of their QS networks. Finally, we will rationally design strains with superior ‘cheating’ strategies that can invade and eliminate a cooperative population.
Throughout this project, we will use a combination of experimental techniques from microbiology, socio-biology, genetics and microscopy together with mathematical analysis tools from systems biology, population genetics and game theory, to study bacterial cooperation and its dependence on the underlying communication network, social complexity and environmental variation.
Max ERC Funding
1 497 996 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym EXPRES
Project Chromatin and transcription in ES cells: from single cells to genome wide views
Researcher (PI) Eran Meshorer
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Starting Grant (StG), LS2, ERC-2011-StG_20101109
Summary How embryonic stem cells (ESCs) maintain their dual capacity to self-renew and to differentiate into all cell types is one of the fundamental questions in biology. Although this question remains largely open, there is growing evidence suggesting that chromatin plasticity is a fundamental hallmark of ESCs, providing their necessary flexibility.
Previously we found that ESCs possess a relatively open chromatin conformation, giving rise to permissive transcriptional program. Here I propose to investigate the mechanisms that support chromatin plasticity and pluripotency in ESCs.
Using a simple biochemical assay which I developed (DCAP: Differential Chromatin Associated Proteins), based on micrococcal nuclease (MNase) digestion combined with multi-dimensional protein identification technology (MudPIT), I seek to identify ESC-specific chromatin proteins. Selected proteins will be knocked-down (or out) and their ESC function will be evaluated.
In addition, I will conduct a hypothesis-driven research using mutant ESCs and epigenetic-related drugs to search for potential mechanisms, (i.e. histone modifications, DNA methylation), that may support chromatin plasticity in ESCs. Based on our intriguing preliminary data, I will also focus on the link between the nuclear lamina and ESC plasticity.
Thirdly, we will analyze non-polyadenylated transcription using genome-wide tiling arrays and RNA-seq. We will design custom microarrays containing the identified sequences, which will allow us to reveal, using ChIP-chip experiments, the mechanistic regulation of the non-polyadenylated transcripts. Finally, we will knockout, using zinc-finger nuclease technology, selected highly conserved candidates in search of their function.
Understanding chromatin regulation, plasticity and function will enable one to intelligently manipulate ESCs to transition between the pluripotent, multipotent and unipotent states and to expedite their use in the clinic.
Summary
How embryonic stem cells (ESCs) maintain their dual capacity to self-renew and to differentiate into all cell types is one of the fundamental questions in biology. Although this question remains largely open, there is growing evidence suggesting that chromatin plasticity is a fundamental hallmark of ESCs, providing their necessary flexibility.
Previously we found that ESCs possess a relatively open chromatin conformation, giving rise to permissive transcriptional program. Here I propose to investigate the mechanisms that support chromatin plasticity and pluripotency in ESCs.
Using a simple biochemical assay which I developed (DCAP: Differential Chromatin Associated Proteins), based on micrococcal nuclease (MNase) digestion combined with multi-dimensional protein identification technology (MudPIT), I seek to identify ESC-specific chromatin proteins. Selected proteins will be knocked-down (or out) and their ESC function will be evaluated.
In addition, I will conduct a hypothesis-driven research using mutant ESCs and epigenetic-related drugs to search for potential mechanisms, (i.e. histone modifications, DNA methylation), that may support chromatin plasticity in ESCs. Based on our intriguing preliminary data, I will also focus on the link between the nuclear lamina and ESC plasticity.
Thirdly, we will analyze non-polyadenylated transcription using genome-wide tiling arrays and RNA-seq. We will design custom microarrays containing the identified sequences, which will allow us to reveal, using ChIP-chip experiments, the mechanistic regulation of the non-polyadenylated transcripts. Finally, we will knockout, using zinc-finger nuclease technology, selected highly conserved candidates in search of their function.
Understanding chromatin regulation, plasticity and function will enable one to intelligently manipulate ESCs to transition between the pluripotent, multipotent and unipotent states and to expedite their use in the clinic.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-12-01, End date: 2016-11-30
