Project acronym 19TH-CENTURY_EUCLID
Project Nineteenth-Century Euclid: Geometry and the Literary Imagination from Wordsworth to Wells
Researcher (PI) Alice Jenkins
Host Institution (HI) UNIVERSITY OF GLASGOW
Call Details Starting Grant (StG), SH4, ERC-2007-StG
Summary This radically interdisciplinary project aims to bring a substantially new field of research – literature and mathematics studies – to prominence as a tool for investigating the culture of nineteenth-century Britain. It will result in three kinds of outcome: a monograph, two interdisciplinary and international colloquia, and a collection of essays. The project focuses on Euclidean geometry as a key element of nineteenth-century literary and scientific culture, showing that it was part of the shared knowledge flowing through elite and popular Romantic and Victorian writing, and figuring notably in the work of very many of the century’s best-known writers. Despite its traditional cultural prestige and educational centrality, geometry has been almost wholly neglected by literary history. This project shows how literature and mathematics studies can draw a new map of nineteenth-century British culture, revitalising our understanding of the Romantic and Victorian imagination through its writing about geometry.
Summary
This radically interdisciplinary project aims to bring a substantially new field of research – literature and mathematics studies – to prominence as a tool for investigating the culture of nineteenth-century Britain. It will result in three kinds of outcome: a monograph, two interdisciplinary and international colloquia, and a collection of essays. The project focuses on Euclidean geometry as a key element of nineteenth-century literary and scientific culture, showing that it was part of the shared knowledge flowing through elite and popular Romantic and Victorian writing, and figuring notably in the work of very many of the century’s best-known writers. Despite its traditional cultural prestige and educational centrality, geometry has been almost wholly neglected by literary history. This project shows how literature and mathematics studies can draw a new map of nineteenth-century British culture, revitalising our understanding of the Romantic and Victorian imagination through its writing about geometry.
Max ERC Funding
323 118 €
Duration
Start date: 2009-01-01, End date: 2011-10-31
Project acronym CONSERVREGCIRCUITRY
Project Conservation and Divergence of Tissue-Specific Transcriptional Regulation
Researcher (PI) Duncan Odom
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS2, ERC-2007-StG
Summary Vertebrates contain hundreds of different cell types which maintain phenotypic identity by a combination of epigenetic programming and genomic regulation. Systems biology approaches are now used in a number of laboratories to determine how transcription factors and chromatin marks pattern the human genome. Despite high conservation of the cellular and molecular function of many mammalian transcription factors, our recent experiments in matched mouse and human tissues indicates that most transcription factor binding events to DNA are very poorly conserved. A hypothesis that could account for this apparent divergence is that the larger regional pattern of transcription factor binding may be conserved. To test this, (1) we are characterizing the global transcriptional profile, chromatin state, and complete genomic occupancy of a set of tissue-specific transcription factors in hepatocytes of strategically chosen mammals; (2) to further identify the precise mechanistic contribution of cis and trans effects, we are comparing transcription factor binding at homologous regions of human and mouse DNA in a mouse line that carries human chromosome 21. Together, these projects will provide insight into the general principles of how transcriptional networks are evolutionarily conserved to regulate cell fate specification and function using a clinically important cell type as a model.
Summary
Vertebrates contain hundreds of different cell types which maintain phenotypic identity by a combination of epigenetic programming and genomic regulation. Systems biology approaches are now used in a number of laboratories to determine how transcription factors and chromatin marks pattern the human genome. Despite high conservation of the cellular and molecular function of many mammalian transcription factors, our recent experiments in matched mouse and human tissues indicates that most transcription factor binding events to DNA are very poorly conserved. A hypothesis that could account for this apparent divergence is that the larger regional pattern of transcription factor binding may be conserved. To test this, (1) we are characterizing the global transcriptional profile, chromatin state, and complete genomic occupancy of a set of tissue-specific transcription factors in hepatocytes of strategically chosen mammals; (2) to further identify the precise mechanistic contribution of cis and trans effects, we are comparing transcription factor binding at homologous regions of human and mouse DNA in a mouse line that carries human chromosome 21. Together, these projects will provide insight into the general principles of how transcriptional networks are evolutionarily conserved to regulate cell fate specification and function using a clinically important cell type as a model.
Max ERC Funding
960 000 €
Duration
Start date: 2008-10-01, End date: 2013-09-30
Project acronym EARLYPOWERONTOLOGIES
Project Causal Structuralist Ontologies in Antiquity: Powers as the basic building block of the worlds of the ancients
Researcher (PI) Anna Marmodoro
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Starting Grant (StG), SH4, ERC-2010-StG_20091209
Summary The project aims to bring about a paradigm shift in our understanding of how the ancients conceived of the universe and its contents over a period of 9 centuries, 600 BC to 300 AD. The driving research hypothesis is that the sole elementary building blocks of nearly all ancient ontologies are powers, from which all there is in the universe is built. Powers are relational properties which are directed towards an end (e.g. the power to heat); thus a world of powers is structured in a web of causal relations. What is revolutionary about such a world is that there is only structure in it; hence, causal structuralist ontologies underlie object-metaphysics or process-metaphysics, and worlds of being and becoming, supplying structures from which objects and processes are derived. Yet such ontologies have never been investigated about ancient thought.
The project’s topic is new: ancient causal structuralism; the speciality is novel too, requiring targeted training of a team of post-doc researchers which will be provided by the applicant and collaborators. The innovativeness of the methodology consists in training ancient philosophy researchers to discern and identify formal aspects of ontologies at the very roots of human rationality – discerning how the ancients built everything out of power structures.
The paradigm shift will generate new knowledge and understanding about the ancient accounts of the world; provide a heuristic vantage point for redrafting the map of the intellectual influences between ancient thinkers; stimulate fruitful debate; and inspire new insights into ancient thought that are literally unthinkable at present. Cognate disciplines that will be affected by the paradigm shift are such as: history of physics; of mathematics; of theology; ancient anthropology.
Summary
The project aims to bring about a paradigm shift in our understanding of how the ancients conceived of the universe and its contents over a period of 9 centuries, 600 BC to 300 AD. The driving research hypothesis is that the sole elementary building blocks of nearly all ancient ontologies are powers, from which all there is in the universe is built. Powers are relational properties which are directed towards an end (e.g. the power to heat); thus a world of powers is structured in a web of causal relations. What is revolutionary about such a world is that there is only structure in it; hence, causal structuralist ontologies underlie object-metaphysics or process-metaphysics, and worlds of being and becoming, supplying structures from which objects and processes are derived. Yet such ontologies have never been investigated about ancient thought.
The project’s topic is new: ancient causal structuralism; the speciality is novel too, requiring targeted training of a team of post-doc researchers which will be provided by the applicant and collaborators. The innovativeness of the methodology consists in training ancient philosophy researchers to discern and identify formal aspects of ontologies at the very roots of human rationality – discerning how the ancients built everything out of power structures.
The paradigm shift will generate new knowledge and understanding about the ancient accounts of the world; provide a heuristic vantage point for redrafting the map of the intellectual influences between ancient thinkers; stimulate fruitful debate; and inspire new insights into ancient thought that are literally unthinkable at present. Cognate disciplines that will be affected by the paradigm shift are such as: history of physics; of mathematics; of theology; ancient anthropology.
Max ERC Funding
1 228 581 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
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 MULTISIGN
Project Multilingual Behaviours In Sign Language Users
Researcher (PI) Ulrike Andrea Hildegard Zeshan
Host Institution (HI) UNIVERSITY OF CENTRAL LANCASHIRE
Call Details Starting Grant (StG), SH4, ERC-2010-StG_20091209
Summary This project examines a range of complex multilingual behaviours in sign language users and pursues three thematically related studies: a) Cross-signing : The development of improvised communication (ad hoc pidgins) between users of different sign languages in language contact situations; b) Sign-speaking : The simultaneous production of sign and speech, where the different structures of both languages are kept largely intact; and c) Sign-switching : Code-switching between sign languages in multilingual sign language users. None of these multilingual behaviours has ever been systematically investigated.
The three studies use both lab-based experimental methodologies and discourse data from natural communicative situations. Subjects are drawn from a group of multilingual, mostly deaf, sign language users from various countries around the world. This project is situated at the crossroads between the domains of sociolinguistics, psycholinguistics, typological, and diachronic approaches to language. Together, the three focused studies break new ground and lay the foundation to a previously uncovered field of research that can be called sign multilingualism studies . This field arises when existing concepts of bi- and multilingualism are brought to bear on sign languages. Of particular interest are phenomena that are peculiar to situations involving sign languages, such as the rapid emergence of improvised inter-languages in cross-signing , or the simultaneous combination of conflicting syntactic structures in sign-speaking .
In addition to the theme of sign multilingualism, the three sub-projects are also united by a particular interest in the meta-linguistic skills that the subjects use in both the experimental and the natural discourse settings. Some of these previously undocumented high-level skills take us right to the limits of linguistic abilities and have wider implications for our understanding of the human language faculty.
Summary
This project examines a range of complex multilingual behaviours in sign language users and pursues three thematically related studies: a) Cross-signing : The development of improvised communication (ad hoc pidgins) between users of different sign languages in language contact situations; b) Sign-speaking : The simultaneous production of sign and speech, where the different structures of both languages are kept largely intact; and c) Sign-switching : Code-switching between sign languages in multilingual sign language users. None of these multilingual behaviours has ever been systematically investigated.
The three studies use both lab-based experimental methodologies and discourse data from natural communicative situations. Subjects are drawn from a group of multilingual, mostly deaf, sign language users from various countries around the world. This project is situated at the crossroads between the domains of sociolinguistics, psycholinguistics, typological, and diachronic approaches to language. Together, the three focused studies break new ground and lay the foundation to a previously uncovered field of research that can be called sign multilingualism studies . This field arises when existing concepts of bi- and multilingualism are brought to bear on sign languages. Of particular interest are phenomena that are peculiar to situations involving sign languages, such as the rapid emergence of improvised inter-languages in cross-signing , or the simultaneous combination of conflicting syntactic structures in sign-speaking .
In addition to the theme of sign multilingualism, the three sub-projects are also united by a particular interest in the meta-linguistic skills that the subjects use in both the experimental and the natural discourse settings. Some of these previously undocumented high-level skills take us right to the limits of linguistic abilities and have wider implications for our understanding of the human language faculty.
Max ERC Funding
1 169 936 €
Duration
Start date: 2011-03-01, End date: 2016-08-31
Project acronym PLASTICSELF
Project The plasticity of the self: experimenting with self-identity in the face of change
Researcher (PI) Emmanouil Tsakiris
Host Institution (HI) ROYAL HOLLOWAY AND BEDFORD NEW COLLEGE
Call Details Starting Grant (StG), SH4, ERC-2010-StG_20091209
Summary We normally entertain a fairly continuous and stable sense of personal identity, as we acknowledge that we are the same person, independently of what happens to us. The question of how our sense of self is maintained or changed across time is a key topic in psychology. Our self must possess sufficient plasticity, that is, adaptive processes of re-organization, to ensure assimilation of changes and a sense of continuity over time. To study the plasticity of the self, we will investigate how the experience of a changing body updates or alters our sense of self, in two parallel projects.
First, we will study what is currently considered to be the most radical change in one’s body, the case of face-transplantation. In face-transplantation, the acquisition of a new face is a medical fact, while the experience of a new identity is an unexplored psychological outcome. We will investigate the plasticity and continuity of the self caused by face-transplantation by testing self-identification in individuals before and after the operation, using experimental psychology and functional neuroimgaing methods. Second, we ask how our own body-image affects the way we perceive other people. We will address this second question by investigating how changes in body-representation, caused by experimental manipulations of bodily illusions, can consequently affect social cognition processes, using experimental and social psychology methods.The question of the plasticity of the self is timely, because the modern self, due to societal, technological and medical advances, seems to be exposed to new, often radical, possibilities of change. The proposed project aims at understanding the basic mechanisms behind the plasticity of the self, by integrating research methods from experimental and social psychology, cognitive neurosciences, and medicine in wide-ranging and innovative ways.”
Summary
We normally entertain a fairly continuous and stable sense of personal identity, as we acknowledge that we are the same person, independently of what happens to us. The question of how our sense of self is maintained or changed across time is a key topic in psychology. Our self must possess sufficient plasticity, that is, adaptive processes of re-organization, to ensure assimilation of changes and a sense of continuity over time. To study the plasticity of the self, we will investigate how the experience of a changing body updates or alters our sense of self, in two parallel projects.
First, we will study what is currently considered to be the most radical change in one’s body, the case of face-transplantation. In face-transplantation, the acquisition of a new face is a medical fact, while the experience of a new identity is an unexplored psychological outcome. We will investigate the plasticity and continuity of the self caused by face-transplantation by testing self-identification in individuals before and after the operation, using experimental psychology and functional neuroimgaing methods. Second, we ask how our own body-image affects the way we perceive other people. We will address this second question by investigating how changes in body-representation, caused by experimental manipulations of bodily illusions, can consequently affect social cognition processes, using experimental and social psychology methods.The question of the plasticity of the self is timely, because the modern self, due to societal, technological and medical advances, seems to be exposed to new, often radical, possibilities of change. The proposed project aims at understanding the basic mechanisms behind the plasticity of the self, by integrating research methods from experimental and social psychology, cognitive neurosciences, and medicine in wide-ranging and innovative ways.”
Max ERC Funding
1 444 460 €
Duration
Start date: 2011-02-01, End date: 2016-07-31
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
