Project acronym BIOPROPERTY
Project Biomedical Research and the Future of Property Rights
Researcher (PI) Javier Lezaun Barreras
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Starting Grant (StG), SH2, ERC-2010-StG_20091209
Summary This research project investigates the dynamics of private and public property in contemporary biomedical research. It will develop an analytical framework combining insights from science and technology studies, economic sociology, and legal and political philosophy, and pursues a social scientific investigation of the evolution of intellectual property rights in three fields of bioscientific research: 1) the use of transgenic research mice; 2) the legal status of totipotent and pluripotent stem cell lines; and 3) modes of collaboration for research and development on neglected diseases. These three domains, and their attendant modes of appropriation, will be compared across three general research themes: a) the production of public scientific goods; b) categories of appropriation; and c) the moral economy of research. The project rests on close observation of research practices in these three domains. The BioProperty research programme will track the trajectories of property rights and property objects in each of the three fields of biomedical research.
Summary
This research project investigates the dynamics of private and public property in contemporary biomedical research. It will develop an analytical framework combining insights from science and technology studies, economic sociology, and legal and political philosophy, and pursues a social scientific investigation of the evolution of intellectual property rights in three fields of bioscientific research: 1) the use of transgenic research mice; 2) the legal status of totipotent and pluripotent stem cell lines; and 3) modes of collaboration for research and development on neglected diseases. These three domains, and their attendant modes of appropriation, will be compared across three general research themes: a) the production of public scientific goods; b) categories of appropriation; and c) the moral economy of research. The project rests on close observation of research practices in these three domains. The BioProperty research programme will track the trajectories of property rights and property objects in each of the three fields of biomedical research.
Max ERC Funding
887 602 €
Duration
Start date: 2011-03-01, End date: 2014-12-31
Project acronym DEBIDEM
Project Defining Belief and Identities in the Eastern Mediterranean:
The Role of Interreligious Debate and Interaction
Researcher (PI) Ioannis Papadogiannakis
Host Institution (HI) KING'S COLLEGE LONDON
Call Details Starting Grant (StG), SH2, ERC-2010-StG_20091209
Summary This project seeks to recover the processes by which religious beliefs and identities were defined through interreligious interaction and debate in the religious culture of a broader social base in the eastern Mediterranean (6-8th centuries AD) through examination of a neglected, unconventional corpus of medieval Greek, Syriac and Arabic literature of debate and disputation (consisting of collections of questions and answers, dialogues among others), treating authors such as Ps. Kaisarios, Anastasios of Sinai, and Ps. Athanasios. These sources help us to understand the kinds of perplexities that were being raised in Christian communities of the eastern Mediterranean as they negotiated a lively and contentious religious and social landscape, and they highlight the multifarious issues which Christian leaders had to be prepared to deal with in their pastoral, pedagogical, and apologetic work. At the same time these collections must be seen as an attempt by Christian authors to work out how Christianity was to define its position with regard to other religions (Hellenism, Judaism and Islam) in a period still characterized by considerable fluidity and change.
As well as writing those doubts, challenges, objections, concerns, issues and anxieties back into the religious history of the eastern Mediterranean, when completed this full-length study of these texts will provide scholars not only with a detailed knowledge of the ways in which religious belief, practice and communities were defined in contrast to other religious systems, and a fuller sense of the religious, social and intellectual history of the eastern Mediterranean but also with a nuanced picture of their self-definition, one which will be more sensitive to the processes that led to its formation.
Summary
This project seeks to recover the processes by which religious beliefs and identities were defined through interreligious interaction and debate in the religious culture of a broader social base in the eastern Mediterranean (6-8th centuries AD) through examination of a neglected, unconventional corpus of medieval Greek, Syriac and Arabic literature of debate and disputation (consisting of collections of questions and answers, dialogues among others), treating authors such as Ps. Kaisarios, Anastasios of Sinai, and Ps. Athanasios. These sources help us to understand the kinds of perplexities that were being raised in Christian communities of the eastern Mediterranean as they negotiated a lively and contentious religious and social landscape, and they highlight the multifarious issues which Christian leaders had to be prepared to deal with in their pastoral, pedagogical, and apologetic work. At the same time these collections must be seen as an attempt by Christian authors to work out how Christianity was to define its position with regard to other religions (Hellenism, Judaism and Islam) in a period still characterized by considerable fluidity and change.
As well as writing those doubts, challenges, objections, concerns, issues and anxieties back into the religious history of the eastern Mediterranean, when completed this full-length study of these texts will provide scholars not only with a detailed knowledge of the ways in which religious belief, practice and communities were defined in contrast to other religious systems, and a fuller sense of the religious, social and intellectual history of the eastern Mediterranean but also with a nuanced picture of their self-definition, one which will be more sensitive to the processes that led to its formation.
Max ERC Funding
1 483 119 €
Duration
Start date: 2011-01-01, End date: 2016-12-31
Project acronym ELABORATE
Project Elucidation of the molecular and functional basis of disease phenotypes in the rat model
Researcher (PI) Timothy Aitman
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Advanced Grant (AdG), LS2, ERC-2010-AdG_20100317
Summary Recent genetic studies have identified hundreds of susceptibility genes for common human diseases but genetic effects are small and identifying underlying mechanisms remains challenging. Rodent models offer significant advantages for analysis of disease phenotypes. Advances in genome resources and gene targeting have increased the attractiveness of the rat model for genetic studies but progress has been hampered by absence of relevant rat genome sequences.
We recently sequenced the genome of the spontaneously hypertensive rat (SHR) and will shortly have completed the Wistar Kyoto (WKY) rat sequence. The SHR genome contains over 750 genes that are completely or partly deleted, or have a frameshift in their open reading frame. These sequence variants, along with variants controlling dysregulated gene expression that we characterised previously, most likely include the major determinants of SHR cardiovascular and metabolic disease phenotypes.
We shall determine the functional consequences of these variants by creating and phenotyping transgenic and knockout rats on the SHR and WKY genetic backgrounds, using transposon-mediated transgenesis and zinc-finger nuclease-mediated gene deletion recently shown to be highly efficient in rats. Genes will be prioritised for study by statistical and informatic analyses using our extensive physiological, gene expression and linkage data in these rat strains, and by comparative analysis with data from human genome-wide association studies. Confirmed rat disease genes will be tested for conserved functions in humans.
These proposals provide a systematic route to elucidating the molecular and functional basis of disease phenotypes in SHR and WKY rats, and for translating these findings to advance understanding of common human diseases.
Summary
Recent genetic studies have identified hundreds of susceptibility genes for common human diseases but genetic effects are small and identifying underlying mechanisms remains challenging. Rodent models offer significant advantages for analysis of disease phenotypes. Advances in genome resources and gene targeting have increased the attractiveness of the rat model for genetic studies but progress has been hampered by absence of relevant rat genome sequences.
We recently sequenced the genome of the spontaneously hypertensive rat (SHR) and will shortly have completed the Wistar Kyoto (WKY) rat sequence. The SHR genome contains over 750 genes that are completely or partly deleted, or have a frameshift in their open reading frame. These sequence variants, along with variants controlling dysregulated gene expression that we characterised previously, most likely include the major determinants of SHR cardiovascular and metabolic disease phenotypes.
We shall determine the functional consequences of these variants by creating and phenotyping transgenic and knockout rats on the SHR and WKY genetic backgrounds, using transposon-mediated transgenesis and zinc-finger nuclease-mediated gene deletion recently shown to be highly efficient in rats. Genes will be prioritised for study by statistical and informatic analyses using our extensive physiological, gene expression and linkage data in these rat strains, and by comparative analysis with data from human genome-wide association studies. Confirmed rat disease genes will be tested for conserved functions in humans.
These proposals provide a systematic route to elucidating the molecular and functional basis of disease phenotypes in SHR and WKY rats, and for translating these findings to advance understanding of common human diseases.
Max ERC Funding
2 476 108 €
Duration
Start date: 2011-06-01, End date: 2017-05-31
Project acronym GAMSOC
Project Gambling in Europe
Researcher (PI) Rebecca Cassidy
Host Institution (HI) GOLDSMITHS' COLLEGE
Call Details Starting Grant (StG), SH2, ERC-2010-StG_20091209
Summary This project uses an innovative anthropological approach to study gambling as a social and cultural activity, and uses these findings to establish a new research paradigm that is technologically astute, internationally focused and aggressively future oriented. Gambling in Europe is worth an estimated E89billion and is a rapidly expanding and changing industry. It is also a source of concern to legislators and consumers. Gambling legislation is not harmonised at the European level. National governments are currently moving at varying speeds
between containment and revenue generation, driven on by operators who use constantly evolving technology to create new markets and exploit loopholes in existing ad hoc and obsolete legislation. Like legislators, the research community has failed to keep pace with these changes and continues to focus on quantifying and categorising gamblers and gambling activities within national boundaries. This project will craft a more critical and powerful alternative. Highly productive and proven anthropological approaches will be applied to four
systematically integrated case studies: the UK remote gambling industry, spread betting among Chinese financial services workers in Europe, land based gaming in Cyprus and gamblers and non-gamblers in the Italo-Slovenian borderlands. The project will establish the value of a systematic ethnographic approach to gambling by conducting research in a number of contrasting settings, across a number of
different scales. It will produce high quality and robust data that will form the basis of a new research paradigm that matches the dynamism and internationalism of the European gambling industry today.
Summary
This project uses an innovative anthropological approach to study gambling as a social and cultural activity, and uses these findings to establish a new research paradigm that is technologically astute, internationally focused and aggressively future oriented. Gambling in Europe is worth an estimated E89billion and is a rapidly expanding and changing industry. It is also a source of concern to legislators and consumers. Gambling legislation is not harmonised at the European level. National governments are currently moving at varying speeds
between containment and revenue generation, driven on by operators who use constantly evolving technology to create new markets and exploit loopholes in existing ad hoc and obsolete legislation. Like legislators, the research community has failed to keep pace with these changes and continues to focus on quantifying and categorising gamblers and gambling activities within national boundaries. This project will craft a more critical and powerful alternative. Highly productive and proven anthropological approaches will be applied to four
systematically integrated case studies: the UK remote gambling industry, spread betting among Chinese financial services workers in Europe, land based gaming in Cyprus and gamblers and non-gamblers in the Italo-Slovenian borderlands. The project will establish the value of a systematic ethnographic approach to gambling by conducting research in a number of contrasting settings, across a number of
different scales. It will produce high quality and robust data that will form the basis of a new research paradigm that matches the dynamism and internationalism of the European gambling industry today.
Max ERC Funding
1 200 000 €
Duration
Start date: 2011-01-01, End date: 2015-07-31
Project acronym GENEVA
Project Genome Evolution in the Animal Kingdom
Researcher (PI) Peter William Harold Holland
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), LS2, ERC-2010-AdG_20100317
Summary Like everything in biology, the genome is a product of evolution. In our own history, mutations that duplicate genes have generated extensive multigene families and classes, including a great diversity of transcriptional regulators involved in development of cells, tissues and organs. For example, two complete genome duplication events occurred in early vertebrate evolution (known as 2R), a third genome duplication occurred at the base of teleost fish (3R), and there were extensive tandem gene duplications in placental mammals. What role did these events play in animal evolution? How do newly duplicate genes diverge in function? Why do tandem gene duplicates evolve in a different way to whole genome duplicates? The proposed research programme aims to resolve these questions. The long-term functional consequences of duplication will be examined by examining how the spectrum of target genes differs, or overlaps, between transcription factors known to have duplicated in the 2R and 3R events. To understand the earliest stages of duplicate gene evolution gene sequences and gene expression will be studied in a spectrum of animals descendent from much more recent genome duplications, including several freshwater fish and desert-living rodents. The contrast between whole genome and tandem gene duplication will be examined in parallel, through genomic and protein-engineering studies of novel homeobox genes that arose in mammalian evolution. The programme of research is novel and will create physical and knowledge-based resources relevant to genomics, evolution, development, physiology and biomedical genetics.
Summary
Like everything in biology, the genome is a product of evolution. In our own history, mutations that duplicate genes have generated extensive multigene families and classes, including a great diversity of transcriptional regulators involved in development of cells, tissues and organs. For example, two complete genome duplication events occurred in early vertebrate evolution (known as 2R), a third genome duplication occurred at the base of teleost fish (3R), and there were extensive tandem gene duplications in placental mammals. What role did these events play in animal evolution? How do newly duplicate genes diverge in function? Why do tandem gene duplicates evolve in a different way to whole genome duplicates? The proposed research programme aims to resolve these questions. The long-term functional consequences of duplication will be examined by examining how the spectrum of target genes differs, or overlaps, between transcription factors known to have duplicated in the 2R and 3R events. To understand the earliest stages of duplicate gene evolution gene sequences and gene expression will be studied in a spectrum of animals descendent from much more recent genome duplications, including several freshwater fish and desert-living rodents. The contrast between whole genome and tandem gene duplication will be examined in parallel, through genomic and protein-engineering studies of novel homeobox genes that arose in mammalian evolution. The programme of research is novel and will create physical and knowledge-based resources relevant to genomics, evolution, development, physiology and biomedical genetics.
Max ERC Funding
1 735 016 €
Duration
Start date: 2011-06-01, End date: 2016-05-31
Project acronym HEALTHCYCLE
Project Economic Cycles, Employment and Health: Disentangling Causal Pathways in a Cross-National Study
Researcher (PI) Mauricio Avendano Pabon
Host Institution (HI) KING'S COLLEGE LONDON
Call Details Starting Grant (StG), SH2, ERC-2010-StG_20091209
Summary Research in economics suggests that business cycles are associated with population health: Physical health deteriorates during economic expansions and improves during recessions. At odds with these findings, research in epidemiology and sociology suggests that individual unemployment and job insecurity are associated with poor health and higher mortality. While studies on the impact of economic cycles have been hampered by the lack individual data to unravel causal pathways, employment studies have not adequately controlled for health selection effects when examining causality. This project aims to advancing understanding by exploiting historical fluctuations in the economy as exogenous shocks to identify causal effects of individual unemployment and job insecurity on health, disentangling the pathways that link business cycles, employment and health. Specifically, this study will assess whether patterns of individual employment induced by economic cycles during the last 50 years are associated with life-course health in 18 countries. The approach is based on a unique linkage of historical data on macro-economic cycles with (a) detailed life history event micro-data on employment and health in 18 countries recently collected in the Survey of Health, Ageing and Retirement in Europe (SHARE), the English Longitudinal study of Ageing (ELSA) and the US Health and Retirement Survey (HRS); and (b) mortality registry data individually linked to occupational histories from national census for entire populations in five European countries in the period 1960-2005. The project integrates insights and methodologies from sociology, epidemiology and economics, elucidating the pathways through which economic fluctuations influence health in societies with different institutions.
Summary
Research in economics suggests that business cycles are associated with population health: Physical health deteriorates during economic expansions and improves during recessions. At odds with these findings, research in epidemiology and sociology suggests that individual unemployment and job insecurity are associated with poor health and higher mortality. While studies on the impact of economic cycles have been hampered by the lack individual data to unravel causal pathways, employment studies have not adequately controlled for health selection effects when examining causality. This project aims to advancing understanding by exploiting historical fluctuations in the economy as exogenous shocks to identify causal effects of individual unemployment and job insecurity on health, disentangling the pathways that link business cycles, employment and health. Specifically, this study will assess whether patterns of individual employment induced by economic cycles during the last 50 years are associated with life-course health in 18 countries. The approach is based on a unique linkage of historical data on macro-economic cycles with (a) detailed life history event micro-data on employment and health in 18 countries recently collected in the Survey of Health, Ageing and Retirement in Europe (SHARE), the English Longitudinal study of Ageing (ELSA) and the US Health and Retirement Survey (HRS); and (b) mortality registry data individually linked to occupational histories from national census for entire populations in five European countries in the period 1960-2005. The project integrates insights and methodologies from sociology, epidemiology and economics, elucidating the pathways through which economic fluctuations influence health in societies with different institutions.
Max ERC Funding
1 273 280 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym IMGAME
Project A new method for cross-cultural and cross-temporal comparison of societies
Researcher (PI) Harold Maurice Collins
Host Institution (HI) CARDIFF UNIVERSITY
Call Details Advanced Grant (AdG), SH2, ERC-2010-AdG_20100407
Summary A new way to compare societies across space and time will be developed. The method is based on the `Imitation Game’, which is related to the `Turing Test’. Non-members’ try convince a judge they are members of minority or excluded groups and vice-versa. Success over a series of repetitions indicates good cultural understanding of the `target’ group. The method could have shown, for example, the extent to which the black slave population of the US had to understand white society to survive, while white society had no need to understand the black population. The proportion of successful identifications over a series of tests is an inverse measure of the degree of understanding. The content of the questions and answers also indicate cultural features of the group and the society.
Initial tests in local conditions have held promise but the method must be refined and proved by producing a database of interesting cross-national and cross-regional comparisons. Is the method resilient enough to provide comparative measures across culturally diverse regions and, potentially, to measure changes over time? By making an initial comparison of European and other regions, which ought to be valuable in itself, it will be shown whether the method is fit to be used, like the Eurobarometer, for a longitudinal audit of change in societies.
The dimensions of comparison are gender relations, ethnic minorities, religion and sexuality. Regions to be compared are Scandinavia, Western Europe, Central Europe and Southern Europe with North and South America included during the final year barring contingencies. An unusual feature of the proposal is the casual employment of graduate students to run the research locally, giving rise to a trained cohort of potential users in a number of countries.
Summary
A new way to compare societies across space and time will be developed. The method is based on the `Imitation Game’, which is related to the `Turing Test’. Non-members’ try convince a judge they are members of minority or excluded groups and vice-versa. Success over a series of repetitions indicates good cultural understanding of the `target’ group. The method could have shown, for example, the extent to which the black slave population of the US had to understand white society to survive, while white society had no need to understand the black population. The proportion of successful identifications over a series of tests is an inverse measure of the degree of understanding. The content of the questions and answers also indicate cultural features of the group and the society.
Initial tests in local conditions have held promise but the method must be refined and proved by producing a database of interesting cross-national and cross-regional comparisons. Is the method resilient enough to provide comparative measures across culturally diverse regions and, potentially, to measure changes over time? By making an initial comparison of European and other regions, which ought to be valuable in itself, it will be shown whether the method is fit to be used, like the Eurobarometer, for a longitudinal audit of change in societies.
The dimensions of comparison are gender relations, ethnic minorities, religion and sexuality. Regions to be compared are Scandinavia, Western Europe, Central Europe and Southern Europe with North and South America included during the final year barring contingencies. An unusual feature of the proposal is the casual employment of graduate students to run the research locally, giving rise to a trained cohort of potential users in a number of countries.
Max ERC Funding
2 260 082 €
Duration
Start date: 2011-06-01, End date: 2016-05-31
Project acronym METABOLICREGULATORS
Project System-wide analysis of regulatory processes that mediate at the boarder of metabolome and proteome
Researcher (PI) Markus Ralser
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary The metabolic network has a modular architecture, is robust to perturbations, and
responds to biological stimuli. The balance of the network, and the passageway of
network substructures to operate at different activity, requires intensive interactions
between the metabolic network, the transcriptome and the proteome. However, the
biochemical mechanisms monitoring the metabolic network are only barely understood.
Changes in network activity are often mediated through so called reporter metabolites:
general -network interconnecting cofactors and reaction substrates - and specific pathway
intermediates. These metabolites bridge the gap between the small molecule and
macromolecular universe of the cell.
Here we propose combining systematic yeast genetics with targeted metabolomics and
proteomics to understand mechanisms of metabolic regulation on a genome-scale level. In
principle, we will elaborate multiple reaction monitoring (MRM) assays that facilitate
quantification of enzymes and intermediates of selected metabolic pathways via liquid
chromatography tandem mass spectrometry. The analysis will be performed on metabolic
processes that influence aging; those will be analyzed and the results validated by
chemical-genetic profiling and competitive lifespan experiments.
The anticipated results will yield in a system-wide picture of interactions between the
metabolome and regulatory components of the cell. Furthermore, it will identify novel
genetic and biochemical interactions of the aging process. Understanding these
mechanisms will stimulate new research directions in Systems Biology and support the
development of therapeutic strategies against diseases of aging.
Summary
The metabolic network has a modular architecture, is robust to perturbations, and
responds to biological stimuli. The balance of the network, and the passageway of
network substructures to operate at different activity, requires intensive interactions
between the metabolic network, the transcriptome and the proteome. However, the
biochemical mechanisms monitoring the metabolic network are only barely understood.
Changes in network activity are often mediated through so called reporter metabolites:
general -network interconnecting cofactors and reaction substrates - and specific pathway
intermediates. These metabolites bridge the gap between the small molecule and
macromolecular universe of the cell.
Here we propose combining systematic yeast genetics with targeted metabolomics and
proteomics to understand mechanisms of metabolic regulation on a genome-scale level. In
principle, we will elaborate multiple reaction monitoring (MRM) assays that facilitate
quantification of enzymes and intermediates of selected metabolic pathways via liquid
chromatography tandem mass spectrometry. The analysis will be performed on metabolic
processes that influence aging; those will be analyzed and the results validated by
chemical-genetic profiling and competitive lifespan experiments.
The anticipated results will yield in a system-wide picture of interactions between the
metabolome and regulatory components of the cell. Furthermore, it will identify novel
genetic and biochemical interactions of the aging process. Understanding these
mechanisms will stimulate new research directions in Systems Biology and support the
development of therapeutic strategies against diseases of aging.
Max ERC Funding
1 499 996 €
Duration
Start date: 2011-06-01, End date: 2016-05-31
Project acronym MIRNET
Project sRNA regulatory networks
Researcher (PI) Eric Alexander Miska
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary MicroRNAs (miRNAs), a large class of ~22 nucleotide non-coding RNAs (sRNAs) found in many plants and animals act to post-transcriptionally regulate gene expression. Approximately 3% of all known human genes encode miRNAs. Important functions for miRNAs in development, physiology and disease are emerging.
Here we propose to identify and characterize miRNA genetic networks by combining forward and reverse genetic approaches, experimental target identification, quantitative cell biology and computational analyses in C. elegans. We will focus our efforts on a set of 14 miRNAs that are conserved between C. elegans and mammals. Specifically, we will test genetic interactions between this panel of miRNA genes and all known genes in C. elegans using synthetic RNAi screens. Based on pilot studies we expect that these screens will identify direct targets of miRNAs as suppressors and genes acting redundantly with miRNA genes as enhancers. In parallel, we will use experimental approaches to identify the direct in vivo targets and upstream transcriptional regulators for these 14 miRNAs. Finally we will use a live assay for miRNA activity to measure the kinetics of the effects of miRNAs on the gene regulatory network.
To our knowledge this is the first study to use synthetic genetic screens to uncover genome-wide miRNA regulatory networks. This project is taking advantage of a number of recent advances in C. elegans technology. We will deliver a unique dataset to further our understanding of the biology of individual miRNAs in C. elegans, the characteristics of miRNA regulatory networks in C. elegans and more generally miRNA-dependent control in animals.
Summary
MicroRNAs (miRNAs), a large class of ~22 nucleotide non-coding RNAs (sRNAs) found in many plants and animals act to post-transcriptionally regulate gene expression. Approximately 3% of all known human genes encode miRNAs. Important functions for miRNAs in development, physiology and disease are emerging.
Here we propose to identify and characterize miRNA genetic networks by combining forward and reverse genetic approaches, experimental target identification, quantitative cell biology and computational analyses in C. elegans. We will focus our efforts on a set of 14 miRNAs that are conserved between C. elegans and mammals. Specifically, we will test genetic interactions between this panel of miRNA genes and all known genes in C. elegans using synthetic RNAi screens. Based on pilot studies we expect that these screens will identify direct targets of miRNAs as suppressors and genes acting redundantly with miRNA genes as enhancers. In parallel, we will use experimental approaches to identify the direct in vivo targets and upstream transcriptional regulators for these 14 miRNAs. Finally we will use a live assay for miRNA activity to measure the kinetics of the effects of miRNAs on the gene regulatory network.
To our knowledge this is the first study to use synthetic genetic screens to uncover genome-wide miRNA regulatory networks. This project is taking advantage of a number of recent advances in C. elegans technology. We will deliver a unique dataset to further our understanding of the biology of individual miRNAs in C. elegans, the characteristics of miRNA regulatory networks in C. elegans and more generally miRNA-dependent control in animals.
Max ERC Funding
1 500 000 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym OD
Project Organizing Disaster. Civil Protection and the Population
Researcher (PI) Michael Guggenheim
Host Institution (HI) GOLDSMITHS' COLLEGE
Call Details Starting Grant (StG), SH2, ERC-2010-StG_20091209
Summary The proposed project takes up the fundamental question of how the state orders society and applies it to an unexpected, but highly insightful case of disasters. It takes disasters as moments when the state attempts to reorder society and thus analyses the encounter between civil protection as state organisation and the population. What happens when civil protection encounters the population in case of disasters? How does civil protection conceive of the population and how does it influence what happens in case of disasters? How does the population conceive of civil protection in turn? By answering these questions the project reacts to omissions of both disaster studies and research on the state. Both of these research traditions tended to either look exclusively at the state or at resistant or subjected citizens. By drawing on Science and Technology Studies and the sociology of expertise these omissions are averted. This allows first looking at civil protection as a knowledge-based and organised attempt to order society. Second it allows understanding disasters as a process involving a reordering of society mediated by knowledge and objects. Combining these approaches allows to precisely analyse the relationship between experts and lay people, without focusing on either of these.
The project seeks to answer the above questions by combining a set of empirical methods, namely document analysis of civil protection manuals, participant observation and visual ethnographies of civil protection trainings and qualitative interviews in the aftermath of flood-disasters. The empirical fields chosen in this project are England, Switzerland and India, to allow for comparison of different forms of centralization and different forms of professionalization of civil protection organisations.
The empirical research progresses in three steps. First, a study of programmatic texts and training manuals of civil protection agencies looks at how civil protection conceives of the relationship between the organisation and the population on paper and how these views have changed along with organisational structures since the 1950ies. Second, ethnographic studies of civil protection training and narrative interviews with civil protection officers look at how civil protection currently conceives of the population in practice and how these views are mediated by recent organisational and technological changes. Last, recent disaster events are used for an interview-based and ethnographic study to look at what happens when civil protection encounters the population.
Summary
The proposed project takes up the fundamental question of how the state orders society and applies it to an unexpected, but highly insightful case of disasters. It takes disasters as moments when the state attempts to reorder society and thus analyses the encounter between civil protection as state organisation and the population. What happens when civil protection encounters the population in case of disasters? How does civil protection conceive of the population and how does it influence what happens in case of disasters? How does the population conceive of civil protection in turn? By answering these questions the project reacts to omissions of both disaster studies and research on the state. Both of these research traditions tended to either look exclusively at the state or at resistant or subjected citizens. By drawing on Science and Technology Studies and the sociology of expertise these omissions are averted. This allows first looking at civil protection as a knowledge-based and organised attempt to order society. Second it allows understanding disasters as a process involving a reordering of society mediated by knowledge and objects. Combining these approaches allows to precisely analyse the relationship between experts and lay people, without focusing on either of these.
The project seeks to answer the above questions by combining a set of empirical methods, namely document analysis of civil protection manuals, participant observation and visual ethnographies of civil protection trainings and qualitative interviews in the aftermath of flood-disasters. The empirical fields chosen in this project are England, Switzerland and India, to allow for comparison of different forms of centralization and different forms of professionalization of civil protection organisations.
The empirical research progresses in three steps. First, a study of programmatic texts and training manuals of civil protection agencies looks at how civil protection conceives of the relationship between the organisation and the population on paper and how these views have changed along with organisational structures since the 1950ies. Second, ethnographic studies of civil protection training and narrative interviews with civil protection officers look at how civil protection currently conceives of the population in practice and how these views are mediated by recent organisational and technological changes. Last, recent disaster events are used for an interview-based and ethnographic study to look at what happens when civil protection encounters the population.
Max ERC Funding
1 180 471 €
Duration
Start date: 2011-01-01, End date: 2015-06-30
Project acronym RECMITMEI
Project Regulating recombination in mitotic and meiotic cells
Researcher (PI) Simon Joseph Boulton
Host Institution (HI) THE FRANCIS CRICK INSTITUTE LIMITED
Call Details Advanced Grant (AdG), LS2, ERC-2010-AdG_20100317
Summary DNA is a highly reactive molecule that is subject to deliberate, spontaneous and environmental damage. One of the most catastrophic lesions in DNA is the double-strand break (DSB), which if left unrepaired can result in cell death, infertility, genome instability and cancer. Homologous recombination (HR) is a largely error-free mechanism of DSB repair that utilizes an intact sister or homologous chromosome as a repair template. Despite considerable progress in understanding the mechanisms of HR, very little is known about how this process is regulated. My lab has made a number of seminal discoveries that have improved our understanding of how HR is regulated in mitotic and meiotic cells. In this ERC proposal, we plan to elucidate the mechanisms that control HR events in mitotic cells and regulate HR pathway choice during meiotic recombination. We will place particular emphasis on defining the roles of RTEL1 and HELQ1 in regulating HR in mitotic and meiotic cells and will determine how dysfunction of these genes contributes to tumorigenesis. Biochemistry and proteomic approaches will be employed to determine how the Fanconi anemia (FA) pathway counteracts error-prone repair by non-homologous end joining (NHEJ), thus favouring HR repair in S-phase. The use of NHEJ inhibitors as a potential treatment of FA will be tested in existing mouse models of FA. Finally, genetic screens and proteomic analysis of HR regulators will be performed in C. elegans to elucidate the mechanisms that regulate the choice between crossover and non-crossover pathways during meiotic HR. Thus, in the work proposed here, my lab will make use of multiple experimental approaches to elucidate the mechanisms for control of HR and the consequences of dysregulated HR on human disease.
Summary
DNA is a highly reactive molecule that is subject to deliberate, spontaneous and environmental damage. One of the most catastrophic lesions in DNA is the double-strand break (DSB), which if left unrepaired can result in cell death, infertility, genome instability and cancer. Homologous recombination (HR) is a largely error-free mechanism of DSB repair that utilizes an intact sister or homologous chromosome as a repair template. Despite considerable progress in understanding the mechanisms of HR, very little is known about how this process is regulated. My lab has made a number of seminal discoveries that have improved our understanding of how HR is regulated in mitotic and meiotic cells. In this ERC proposal, we plan to elucidate the mechanisms that control HR events in mitotic cells and regulate HR pathway choice during meiotic recombination. We will place particular emphasis on defining the roles of RTEL1 and HELQ1 in regulating HR in mitotic and meiotic cells and will determine how dysfunction of these genes contributes to tumorigenesis. Biochemistry and proteomic approaches will be employed to determine how the Fanconi anemia (FA) pathway counteracts error-prone repair by non-homologous end joining (NHEJ), thus favouring HR repair in S-phase. The use of NHEJ inhibitors as a potential treatment of FA will be tested in existing mouse models of FA. Finally, genetic screens and proteomic analysis of HR regulators will be performed in C. elegans to elucidate the mechanisms that regulate the choice between crossover and non-crossover pathways during meiotic HR. Thus, in the work proposed here, my lab will make use of multiple experimental approaches to elucidate the mechanisms for control of HR and the consequences of dysregulated HR on human disease.
Max ERC Funding
2 379 104 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
Project acronym SIT-SG
Project Security in transition: An Interdisciplinary Investigation into the Security gap
Researcher (PI) Mary Kaldor
Host Institution (HI) LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE
Call Details Advanced Grant (AdG), SH2, ERC-2010-AdG_20100407
Summary The twentieth century model of security, based on the rule of law and policing within nation-states and conventional military forces externally is no longer easily applicable to twenty first century global security risks. The security gap refers to the fact that millions of people live in situations of intolerable insecurity as a consequence of armed conflict, organised crime, terrorism, financial crisis, poverty and inequality, environmental degradation, vulnerability to natural disasters to name but some of these risks and yet current public security provision is not designed to address these sources of insecurity and, indeed, as recent wars in Iraq and Afghanistan have shown, sometimes makes them worse.
Security in transition’ is about investigating and identifying the nature of the security gap and tracking the ways in which public and private agents are adapting. It has five components: narratives; indicators; rules; tools; and geographies
Summary
The twentieth century model of security, based on the rule of law and policing within nation-states and conventional military forces externally is no longer easily applicable to twenty first century global security risks. The security gap refers to the fact that millions of people live in situations of intolerable insecurity as a consequence of armed conflict, organised crime, terrorism, financial crisis, poverty and inequality, environmental degradation, vulnerability to natural disasters to name but some of these risks and yet current public security provision is not designed to address these sources of insecurity and, indeed, as recent wars in Iraq and Afghanistan have shown, sometimes makes them worse.
Security in transition’ is about investigating and identifying the nature of the security gap and tracking the ways in which public and private agents are adapting. It has five components: narratives; indicators; rules; tools; and geographies
Max ERC Funding
2 391 670 €
Duration
Start date: 2011-06-01, End date: 2016-11-30
Project acronym TB-IMMUNOGEN
Project Understanding genetic control of global gene expression in human macrophages to discover new immune mechanisms protecting from tuberculosis
Researcher (PI) Sergey Nezhentsev
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary Tuberculosis (TB) is a major global problem that urgently requires new preventive and therapeutic approaches. Only minority of people infected with M. tuberculosis develops active TB. Genetic studies provide an unbiased way to scan the whole human genome to find sequence polymorphisms that predispose to TB. Therefore, we have established the world s largest sample collection for TB genetic studies. Now we genotype 6,000 HIV-negative patients with pulmonary TB and 6,000 healthy controls at ~1 million polymorphic sites across the whole genome. This genome-wide association study (GWAS) will allow us to compare frequency of genetic variants among patients and controls to find genes that protect from TB.
Given that susceptibility to TB is a complex disease, a complementary strategy in genetic research is to identify variants that control intermediate cellular phenotypes. Here, for the first time I will undertake a large-scale study to identify polymorphisms that control gene expression in human macrophages, cells that play key role in protection from M. tuberculosis. We will study in vitro global gene expression in uninfected and M. tuberculosis-infected macrophages from hundreds of healthy volunteers correlating it with the genome-wide genotype data of these subjects. This will allow us to identify variants that regulate differential gene expression in macrophages upon M. tuberculosis infection. We will also study functional effects of the polymorphisms associated with TB risk in the previous and ongoing studies. Taken together these experiments will discover genes and biological pathways involved in protection from M. tuberculosis and will characterise macrophage transcription profile of subjects that are genetically predisposed to TB.
Summary
Tuberculosis (TB) is a major global problem that urgently requires new preventive and therapeutic approaches. Only minority of people infected with M. tuberculosis develops active TB. Genetic studies provide an unbiased way to scan the whole human genome to find sequence polymorphisms that predispose to TB. Therefore, we have established the world s largest sample collection for TB genetic studies. Now we genotype 6,000 HIV-negative patients with pulmonary TB and 6,000 healthy controls at ~1 million polymorphic sites across the whole genome. This genome-wide association study (GWAS) will allow us to compare frequency of genetic variants among patients and controls to find genes that protect from TB.
Given that susceptibility to TB is a complex disease, a complementary strategy in genetic research is to identify variants that control intermediate cellular phenotypes. Here, for the first time I will undertake a large-scale study to identify polymorphisms that control gene expression in human macrophages, cells that play key role in protection from M. tuberculosis. We will study in vitro global gene expression in uninfected and M. tuberculosis-infected macrophages from hundreds of healthy volunteers correlating it with the genome-wide genotype data of these subjects. This will allow us to identify variants that regulate differential gene expression in macrophages upon M. tuberculosis infection. We will also study functional effects of the polymorphisms associated with TB risk in the previous and ongoing studies. Taken together these experiments will discover genes and biological pathways involved in protection from M. tuberculosis and will characterise macrophage transcription profile of subjects that are genetically predisposed to TB.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-01-01, End date: 2015-12-31