Project acronym ADAPT
Project Life in a cold climate: the adaptation of cereals to new environments and the establishment of agriculture in Europe
Researcher (PI) Terence Austen Brown
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Country United Kingdom
Call Details Advanced Grant (AdG), SH6, ERC-2013-ADG
Summary "This project explores the concept of agricultural spread as analogous to enforced climate change and asks how cereals adapted to new environments when agriculture was introduced into Europe. Archaeologists have long recognized that the ecological pressures placed on crops would have had an impact on the spread and subsequent development of agriculture, but previously there has been no means of directly assessing the scale and nature of this impact. Recent work that I have directed has shown how such a study could be carried out, and the purpose of this project is to exploit these breakthroughs with the goal of assessing the influence of environmental adaptation on the spread of agriculture, its adoption as the primary subsistence strategy, and the subsequent establishment of farming in different parts of Europe. This will correct the current imbalance between our understanding of the human and environmental dimensions to the domestication of Europe. I will use methods from population genomics to identify loci within the barley and wheat genomes that have undergone selection since the beginning of cereal cultivation in Europe. I will then use ecological modelling to identify those loci whose patterns of selection are associated with ecogeographical variables and hence represent adaptations to local environmental conditions. I will assign dates to the periods when adaptations occurred by sequencing ancient DNA from archaeobotanical assemblages and by computer methods that enable the temporal order of adaptations to be deduced. I will then synthesise the information on environmental adaptations with dating evidence for the spread of agriculture in Europe, which reveals pauses that might be linked to environmental adaptation, with demographic data that indicate regions where Neolithic populations declined, possibly due to inadequate crop productivity, and with an archaeobotanical database showing changes in the prevalence of individual cereals in different regions."
Summary
"This project explores the concept of agricultural spread as analogous to enforced climate change and asks how cereals adapted to new environments when agriculture was introduced into Europe. Archaeologists have long recognized that the ecological pressures placed on crops would have had an impact on the spread and subsequent development of agriculture, but previously there has been no means of directly assessing the scale and nature of this impact. Recent work that I have directed has shown how such a study could be carried out, and the purpose of this project is to exploit these breakthroughs with the goal of assessing the influence of environmental adaptation on the spread of agriculture, its adoption as the primary subsistence strategy, and the subsequent establishment of farming in different parts of Europe. This will correct the current imbalance between our understanding of the human and environmental dimensions to the domestication of Europe. I will use methods from population genomics to identify loci within the barley and wheat genomes that have undergone selection since the beginning of cereal cultivation in Europe. I will then use ecological modelling to identify those loci whose patterns of selection are associated with ecogeographical variables and hence represent adaptations to local environmental conditions. I will assign dates to the periods when adaptations occurred by sequencing ancient DNA from archaeobotanical assemblages and by computer methods that enable the temporal order of adaptations to be deduced. I will then synthesise the information on environmental adaptations with dating evidence for the spread of agriculture in Europe, which reveals pauses that might be linked to environmental adaptation, with demographic data that indicate regions where Neolithic populations declined, possibly due to inadequate crop productivity, and with an archaeobotanical database showing changes in the prevalence of individual cereals in different regions."
Max ERC Funding
2 492 964 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym BEEHIVE
Project Bridging the Evolution and Epidemiology of HIV in Europe
Researcher (PI) Christopher Fraser
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Advanced Grant (AdG), LS2, ERC-2013-ADG
Summary The aim of the BEEHIVE project is to generate novel insight into HIV biology, evolution and epidemiology, leveraging next-generation high-throughput sequencing and bioinformatics to produce and analyse whole-genomes of viruses from approximately 3,000 European HIV-1 infected patients. These patients have known dates of infection spread over the last 25 years, good clinical follow up, and a wide range of clinical prognostic indicators and outcomes. The primary objective is to discover the viral genetic determinants of severity of infection and set-point viral load. This primary objective is high-risk & blue-skies: there is ample indirect evidence of polymorphisms that alter virulence, but they have never been identified, and it is not known how easy they are to discover. However, the project is also high-reward: it could lead to a substantial shift in the understanding of HIV disease.
Technologically, the BEEHIVE project will deliver new approaches for undertaking whole genome association studies on RNA viruses, including delivering an innovative high-throughput bioinformatics pipeline for handling genetically diverse viral quasi-species data (with viral diversity both within and between infected patients).
The project also includes secondary and tertiary objectives that address critical open questions in HIV epidemiology and evolution. The secondary objective is to use viral genetic sequences allied to mathematical epidemic models to better understand the resurgent European epidemic amongst high-risk groups, especially men who have sex with men. The aim will not just be to establish who is at risk of infection, which is known from conventional epidemiological approaches, but also to characterise the risk factors for onwards transmission of the virus. Tertiary objectives involve understanding the relationship between the genetic diversity within viral samples, indicative of on-going evolution or dual infections, to clinical outcomes.
Summary
The aim of the BEEHIVE project is to generate novel insight into HIV biology, evolution and epidemiology, leveraging next-generation high-throughput sequencing and bioinformatics to produce and analyse whole-genomes of viruses from approximately 3,000 European HIV-1 infected patients. These patients have known dates of infection spread over the last 25 years, good clinical follow up, and a wide range of clinical prognostic indicators and outcomes. The primary objective is to discover the viral genetic determinants of severity of infection and set-point viral load. This primary objective is high-risk & blue-skies: there is ample indirect evidence of polymorphisms that alter virulence, but they have never been identified, and it is not known how easy they are to discover. However, the project is also high-reward: it could lead to a substantial shift in the understanding of HIV disease.
Technologically, the BEEHIVE project will deliver new approaches for undertaking whole genome association studies on RNA viruses, including delivering an innovative high-throughput bioinformatics pipeline for handling genetically diverse viral quasi-species data (with viral diversity both within and between infected patients).
The project also includes secondary and tertiary objectives that address critical open questions in HIV epidemiology and evolution. The secondary objective is to use viral genetic sequences allied to mathematical epidemic models to better understand the resurgent European epidemic amongst high-risk groups, especially men who have sex with men. The aim will not just be to establish who is at risk of infection, which is known from conventional epidemiological approaches, but also to characterise the risk factors for onwards transmission of the virus. Tertiary objectives involve understanding the relationship between the genetic diversity within viral samples, indicative of on-going evolution or dual infections, to clinical outcomes.
Max ERC Funding
2 499 739 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym BESTDECISION
Project "Behavioural Economics and Strategic Decision Making: Theory, Empirics, and Experiments"
Researcher (PI) Vincent Paul Crawford
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Advanced Grant (AdG), SH1, ERC-2013-ADG
Summary "I will study questions of central microeconomic importance via interwoven theoretical, empirical, and experimental analyses, from a behavioural perspective combining standard methods with assumptions that better reflect evidence on behaviour and psychological insights. The contributions of behavioural economics have been widely recognized, but the benefits of its insights are far from fully realized. I propose four lines of inquiry that focus on how institutions interact with cognition and behaviour, chosen for their potential to reshape our understanding of important questions and their synergies across lines.
The first line will study nonparametric identification and estimation of reference-dependent versions of the standard microeconomic model of consumer demand or labour supply, the subject of hundreds of empirical studies and perhaps the single most important model in microeconomics. It will allow such studies to consider relevant behavioural factors without imposing structural assumptions as in previous work.
The second line will analyze history-dependent learning in financial crises theoretically and experimentally, with the goal of quantifying how market structure influences the likelihood of a crisis.
The third line will study strategic thinking experimentally, using a powerful new design that links subjects’ searches for hidden payoff information (“eye-movements”) much more directly to thinking.
The fourth line will significantly advance Myerson and Satterthwaite’s analyses of optimal design of bargaining rules and auctions, which first went beyond the analysis of given institutions to study what is possible by designing new institutions, replacing their equilibrium assumption with a nonequilibrium model that is well supported by experiments.
The synergies among these four lines’ theoretical analyses, empirical methods, and data analyses will accelerate progress on each line well beyond what would be possible in a piecemeal approach."
Summary
"I will study questions of central microeconomic importance via interwoven theoretical, empirical, and experimental analyses, from a behavioural perspective combining standard methods with assumptions that better reflect evidence on behaviour and psychological insights. The contributions of behavioural economics have been widely recognized, but the benefits of its insights are far from fully realized. I propose four lines of inquiry that focus on how institutions interact with cognition and behaviour, chosen for their potential to reshape our understanding of important questions and their synergies across lines.
The first line will study nonparametric identification and estimation of reference-dependent versions of the standard microeconomic model of consumer demand or labour supply, the subject of hundreds of empirical studies and perhaps the single most important model in microeconomics. It will allow such studies to consider relevant behavioural factors without imposing structural assumptions as in previous work.
The second line will analyze history-dependent learning in financial crises theoretically and experimentally, with the goal of quantifying how market structure influences the likelihood of a crisis.
The third line will study strategic thinking experimentally, using a powerful new design that links subjects’ searches for hidden payoff information (“eye-movements”) much more directly to thinking.
The fourth line will significantly advance Myerson and Satterthwaite’s analyses of optimal design of bargaining rules and auctions, which first went beyond the analysis of given institutions to study what is possible by designing new institutions, replacing their equilibrium assumption with a nonequilibrium model that is well supported by experiments.
The synergies among these four lines’ theoretical analyses, empirical methods, and data analyses will accelerate progress on each line well beyond what would be possible in a piecemeal approach."
Max ERC Funding
1 985 373 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym COS
Project "The Cult of Saints: a christendom-wide study of its origins, spread and development"
Researcher (PI) Bryan Ward-Perkins
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Advanced Grant (AdG), SH6, ERC-2013-ADG
Summary "An investigation of the origins and development of a central feature of late-antique, medieval and modern culture: the belief that dead saints can act as mediators between a distant God and humankind, and that they are active on earth in many different ways (such as healing the sick, punishing the irreverent, or even controlling the weather).
The project will investigate the emergence of this belief by systematically collecting all the available evidence - across several academic disciplines and six linguistic cultures (Latin, Greek, Syriac, Coptic, Armenian and Georgian), from the first stirrings of the phenomenon in the third century until around the year 700, by which time the cult of saints was fully developed and firmly rooted throughout the Christian world, from Ireland to Iran.
The work will be done by a team of researchers (under expert supervision for four of the eastern languages), closely co-ordinated by the PI. The project will operate concurrently at two levels. The individual researchers will produce free-standing regional studies on aspects of the cult of saints that are essential to the wider project, but at present under-researched. While doing this, they will collect the full range of evidence from their regions within a single searchable database. This will provide the basis for a christendom-wide monograph on the emergence of the cult of saints authored by the PI, and also the context essential to give breadth and depth to the regional studies.
For the first time it will be possible to tell the history of the emergence of the cult of saints across the full geographical and cultural range of early Christendom. Of great importance in itself, this will also link, and thereby enhance, the many pre-existing works of scholarship on aspects of the cult of saints.
The ‘Cult of Saints’ will result in a major summative monograph, a comprehensive international conference, a series of ground-breaking regional studies, and a freely-available database."
Summary
"An investigation of the origins and development of a central feature of late-antique, medieval and modern culture: the belief that dead saints can act as mediators between a distant God and humankind, and that they are active on earth in many different ways (such as healing the sick, punishing the irreverent, or even controlling the weather).
The project will investigate the emergence of this belief by systematically collecting all the available evidence - across several academic disciplines and six linguistic cultures (Latin, Greek, Syriac, Coptic, Armenian and Georgian), from the first stirrings of the phenomenon in the third century until around the year 700, by which time the cult of saints was fully developed and firmly rooted throughout the Christian world, from Ireland to Iran.
The work will be done by a team of researchers (under expert supervision for four of the eastern languages), closely co-ordinated by the PI. The project will operate concurrently at two levels. The individual researchers will produce free-standing regional studies on aspects of the cult of saints that are essential to the wider project, but at present under-researched. While doing this, they will collect the full range of evidence from their regions within a single searchable database. This will provide the basis for a christendom-wide monograph on the emergence of the cult of saints authored by the PI, and also the context essential to give breadth and depth to the regional studies.
For the first time it will be possible to tell the history of the emergence of the cult of saints across the full geographical and cultural range of early Christendom. Of great importance in itself, this will also link, and thereby enhance, the many pre-existing works of scholarship on aspects of the cult of saints.
The ‘Cult of Saints’ will result in a major summative monograph, a comprehensive international conference, a series of ground-breaking regional studies, and a freely-available database."
Max ERC Funding
2 499 240 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym DEVOCHROMO
Project Chromosome structure and genome organization in early mammalian development
Researcher (PI) Peter Fraser
Host Institution (HI) THE BABRAHAM INSTITUTE
Country United Kingdom
Call Details Advanced Grant (AdG), LS2, ERC-2013-ADG
Summary "The spatial organization of the genome inside the cell nucleus is tissue-specific and has been linked to several nuclear processes including gene activation, gene silencing, genomic imprinting, gene co-regulation, genome maintenance, DNA replication, DNA repair, chromosomal translocations and X chromosome inactivation. In fact, just about any nuclear/genome function has a spatial component that has been implicated in its control. We know surprisingly little about chromosome conformation and spatial organization or how they are established. The extent to which they are a cause or consequence of genome functions are current topics of considerable debate, however emerging data from my group and many other groups world-wide indicate that nuclear location and organization are drivers of genome functions, which in cooperation with other features including epigenetic marks, non-coding RNAs and trans-factor binding bring about genome control. Thus, genome spatial organization can be considered on a par with other epigenetic features that together contribute to overall genome control. The classical paradigm of early mammalian development arguably represents the most dramatic and yet least understood process of genome reprogramming, where a single cell undergoes a series of divisions to ultimately give rise to the hundreds of different cell types found in a mature organism. Study of pre-implantation embryo development is hindered by the very nature of the life form, composed of extremely low cell numbers at each stage, which severely limits the options for investigation. My lab has recently developed a novel technique called single cell Hi-C, which has the power to detect tens of thousands of simultaneous chromatin contacts from a single cell. In this application I propose to apply this technology to study chromosome structure and genome organization during mouse pre-implantation development along with single cell transcriptome analyses from the same cells."
Summary
"The spatial organization of the genome inside the cell nucleus is tissue-specific and has been linked to several nuclear processes including gene activation, gene silencing, genomic imprinting, gene co-regulation, genome maintenance, DNA replication, DNA repair, chromosomal translocations and X chromosome inactivation. In fact, just about any nuclear/genome function has a spatial component that has been implicated in its control. We know surprisingly little about chromosome conformation and spatial organization or how they are established. The extent to which they are a cause or consequence of genome functions are current topics of considerable debate, however emerging data from my group and many other groups world-wide indicate that nuclear location and organization are drivers of genome functions, which in cooperation with other features including epigenetic marks, non-coding RNAs and trans-factor binding bring about genome control. Thus, genome spatial organization can be considered on a par with other epigenetic features that together contribute to overall genome control. The classical paradigm of early mammalian development arguably represents the most dramatic and yet least understood process of genome reprogramming, where a single cell undergoes a series of divisions to ultimately give rise to the hundreds of different cell types found in a mature organism. Study of pre-implantation embryo development is hindered by the very nature of the life form, composed of extremely low cell numbers at each stage, which severely limits the options for investigation. My lab has recently developed a novel technique called single cell Hi-C, which has the power to detect tens of thousands of simultaneous chromatin contacts from a single cell. In this application I propose to apply this technology to study chromosome structure and genome organization during mouse pre-implantation development along with single cell transcriptome analyses from the same cells."
Max ERC Funding
2 401 393 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym DISEASES
Project The Diseases of Modern Life: Nineteenth-Century Perspectives
Researcher (PI) Sally Shuttleworth
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Advanced Grant (AdG), SH5, ERC-2013-ADG
Summary "In our current ‘Information Age’ we suffer as never before, it is claimed, from the stresses of an overload of information, and the speed of global networks. The Victorians diagnosed similar problems in the nineteenth century. The medic James Crichton Browne spoke in 1860 of the ‘velocity of thought and action’ now required, and of the stresses imposed on the brain forced to process in a month more information ‘than was required of our grandfathers in the course of a lifetime’. This project will explore the phenomena of stress and overload, and other disorders associated in the nineteenth century with the problems of modernity, as expressed in the literature, science and medicine of the period, tracking the circulation of ideas across these diverse areas. Taking its framework from Diseases of Modern Life (1876) by the medical reformer, Benjamin Ward Richardson, it will explore ‘diseases from worry and mental strain’, as experienced in the professions, ‘lifestyle’ diseases such as the abuse of alcohol and narcotics, and also diseases from environmental pollution. This study will return to the holistic, integrative vision of the Victorians, as expressed in the science and in the great novels of the period, exploring the connections drawn between physiological, psychological and social health, or disease. Particular areas of focus will be: diseases of finance and speculation; diseases associated with particular professions; alcohol and drug addiction amidst the middle classes; travel for health; education and over-pressure in the classroom; the development of phobias and nervous disorders; and the imaginative construction of utopias and dystopias, in relation to health and disease. In its depth and range the project will take scholarship into radically new ground, breaking through the compartmentalization of psychiatric, environmental or literary history, and offering new ways of contextualising the problems of modernity facing us in the twenty-first century."
Summary
"In our current ‘Information Age’ we suffer as never before, it is claimed, from the stresses of an overload of information, and the speed of global networks. The Victorians diagnosed similar problems in the nineteenth century. The medic James Crichton Browne spoke in 1860 of the ‘velocity of thought and action’ now required, and of the stresses imposed on the brain forced to process in a month more information ‘than was required of our grandfathers in the course of a lifetime’. This project will explore the phenomena of stress and overload, and other disorders associated in the nineteenth century with the problems of modernity, as expressed in the literature, science and medicine of the period, tracking the circulation of ideas across these diverse areas. Taking its framework from Diseases of Modern Life (1876) by the medical reformer, Benjamin Ward Richardson, it will explore ‘diseases from worry and mental strain’, as experienced in the professions, ‘lifestyle’ diseases such as the abuse of alcohol and narcotics, and also diseases from environmental pollution. This study will return to the holistic, integrative vision of the Victorians, as expressed in the science and in the great novels of the period, exploring the connections drawn between physiological, psychological and social health, or disease. Particular areas of focus will be: diseases of finance and speculation; diseases associated with particular professions; alcohol and drug addiction amidst the middle classes; travel for health; education and over-pressure in the classroom; the development of phobias and nervous disorders; and the imaginative construction of utopias and dystopias, in relation to health and disease. In its depth and range the project will take scholarship into radically new ground, breaking through the compartmentalization of psychiatric, environmental or literary history, and offering new ways of contextualising the problems of modernity facing us in the twenty-first century."
Max ERC Funding
2 362 659 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym EGO-MEDIA
Project Ego-media: The impact of new media on forms and practices of self-presentation
Researcher (PI) Max William Mill Saunders
Host Institution (HI) KING'S COLLEGE LONDON
Country United Kingdom
Call Details Advanced Grant (AdG), SH5, ERC-2013-ADG
Summary Ego-media: The impact of new media on forms and practices of self-presentation
This project aims to study the impact of new media on autobiographical narratives: an impact increasing as habits and practices of self-presentation evolve rapidly in response to constantly fast-changing technology. It will analyse the range of ways in which autobiographical forms and discursive practices are being transformed at the frontier of technological change; then consider the implications of the new forms and practices for such notions as autobiography, selfhood, subjectivity, individuality, self-intelligibility, agency, creativity, privacy, and sociability. Based in the interdisciplinary Centre for Life-Writing Research in the School of Arts and Humanities at King’s College London, it will combine a humanistic, life-writing theory approach with an interdisciplinary methodology, in collaboration with researchers from Sociolinguistics, Culture Media and Creative Industries, Digital Humanities, Medical Humanities, Psychiatry, War Studies, and Education.
Keywords:
Life-writing, Self-Presentation, Autobiography, Subjectivity, Agency, New Media, Social Media, Immediacy, Discourse, Digital Narratives, Internet, Web 2.0
Summary
Ego-media: The impact of new media on forms and practices of self-presentation
This project aims to study the impact of new media on autobiographical narratives: an impact increasing as habits and practices of self-presentation evolve rapidly in response to constantly fast-changing technology. It will analyse the range of ways in which autobiographical forms and discursive practices are being transformed at the frontier of technological change; then consider the implications of the new forms and practices for such notions as autobiography, selfhood, subjectivity, individuality, self-intelligibility, agency, creativity, privacy, and sociability. Based in the interdisciplinary Centre for Life-Writing Research in the School of Arts and Humanities at King’s College London, it will combine a humanistic, life-writing theory approach with an interdisciplinary methodology, in collaboration with researchers from Sociolinguistics, Culture Media and Creative Industries, Digital Humanities, Medical Humanities, Psychiatry, War Studies, and Education.
Keywords:
Life-writing, Self-Presentation, Autobiography, Subjectivity, Agency, New Media, Social Media, Immediacy, Discourse, Digital Narratives, Internet, Web 2.0
Max ERC Funding
2 206 994 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym EMPSI
Project Receptors, Channels and Transporters:
Development and Application of Novel Technologies for Structure Determination
Researcher (PI) Christopher Gordon Tate
Host Institution (HI) MEDICAL RESEARCH COUNCIL
Country United Kingdom
Call Details Advanced Grant (AdG), LS1, ERC-2013-ADG
Summary Structure determination of G protein-coupled receptors (GPCRs) has been exceedingly successful over the last 5 years due to the development of complimentary generic methodologies that will now allow the structure determination of virtually any GPCR. However, these technologies address only two aspects of the process, namely the stability of the receptors during purification and the ability to form well-diffracting crystals. The strategies also apply only to GPCRs and not transporters or ion channels. The recent successes have been of GPCRs that are expressed in either yeasts or in insect cells using the baculovirus expression system, but many membrane proteins are expressed poorly in these systems or may be expressed in a misfolded non-functional form. A second issue with the future structure determination of GPCRs is the lack of generic technologies to allow the crystallisation of arrestin-GPCR and G protein-GPCR complexes. Although one G protein GPCR complex has been crystallised this was exceedingly diffciult and resulted in poor resolution of the GPCR component of the complex. We believe that it is possible to thermostabilise both arrestin and heterotrimeric G proteins, which will allow a simplified strategy for the crystallisation and structure determination of GPCR complexes. This is based on the development of the strategy of conformational thermostabilisation of GPCRs developed in our lab that has resulted in the structure determination of 3 different GPCRs bound to either antagonists, partial agonists, full agonists and/or biased agonists.
The aims are:
1. The development of generic methodology for the production of eukaryotic membrane proteins in mammalian cells.
2. The development of a thermostable functional arrestin mutant
3. Structures of β1-adrenoceptor, adenosine A2A receptor and angiotensin receptor bound to a G protein and arrestin
4. Understanding the role of each amino acid residue in the activation process of GPCRs through saturation mutagenes
Summary
Structure determination of G protein-coupled receptors (GPCRs) has been exceedingly successful over the last 5 years due to the development of complimentary generic methodologies that will now allow the structure determination of virtually any GPCR. However, these technologies address only two aspects of the process, namely the stability of the receptors during purification and the ability to form well-diffracting crystals. The strategies also apply only to GPCRs and not transporters or ion channels. The recent successes have been of GPCRs that are expressed in either yeasts or in insect cells using the baculovirus expression system, but many membrane proteins are expressed poorly in these systems or may be expressed in a misfolded non-functional form. A second issue with the future structure determination of GPCRs is the lack of generic technologies to allow the crystallisation of arrestin-GPCR and G protein-GPCR complexes. Although one G protein GPCR complex has been crystallised this was exceedingly diffciult and resulted in poor resolution of the GPCR component of the complex. We believe that it is possible to thermostabilise both arrestin and heterotrimeric G proteins, which will allow a simplified strategy for the crystallisation and structure determination of GPCR complexes. This is based on the development of the strategy of conformational thermostabilisation of GPCRs developed in our lab that has resulted in the structure determination of 3 different GPCRs bound to either antagonists, partial agonists, full agonists and/or biased agonists.
The aims are:
1. The development of generic methodology for the production of eukaryotic membrane proteins in mammalian cells.
2. The development of a thermostable functional arrestin mutant
3. Structures of β1-adrenoceptor, adenosine A2A receptor and angiotensin receptor bound to a G protein and arrestin
4. Understanding the role of each amino acid residue in the activation process of GPCRs through saturation mutagenes
Max ERC Funding
2 378 162 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym EVOCAN
Project Why do cancers occur where they do? A genetic and evolutionary approach
Researcher (PI) Ian Phlip Mark Tomlinson
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Advanced Grant (AdG), LS2, ERC-2013-ADG
Summary "Tumorigenesis is a form of somatic evolution, a topical subject given the advent of cancer genome sequencing. However, we contend that some features of Darwinian evolution have been neglected when cancer is studied, as have some aspects of evolution that are special to cancers. For example, tumours comprise an expanding population of cells, cancers must occur within a normal human lifespan, and genotypes detrimental to growth of the tumour as a whole may be selected. These factors may render invalid the classical model in which successive mutations with large advantages arise and spread through the tumour in selective sweeps. To incorporate these neglected features and to test how tumorigenesis depends on factors such as mutation rate, selection and size constraints, we shall set up a comprehensive model of tumour growth incorporating cell birth, death, division and mutation parameters. We shall examine specific aspects of cancer-as-evolution in mice. By marking mutant clones using fluorescent proteins, we can track them and see how they persist, spread and die. We shall also determine the mutation profiles and genetic diversity of mutant clones and whole tumours in mice and humans using next-generation sequencing. Specific experiments will determine: (i) the fate of new advantageous clones arising in an existing tumour; (ii) whether new disadvantageous clones can persist in tumours; (iii) whether apparently maladaptive traits for tumour growth, such as suppressing the growth of competitors, can be selected; (iv) why do housekeeper gene mutations cause cancer in specific sites; (v) can cancer cells have too much genomic instability; and (vi) whether all cancers develop owing to driver mutations with big effects, or are there “mini-drivers” of tumorigenesis? There will be continual cross-talk between the experimental and modelling work. The results of the project will enhance our basic understanding of tumorigenesis and suggest strategies for anticancer therapy."
Summary
"Tumorigenesis is a form of somatic evolution, a topical subject given the advent of cancer genome sequencing. However, we contend that some features of Darwinian evolution have been neglected when cancer is studied, as have some aspects of evolution that are special to cancers. For example, tumours comprise an expanding population of cells, cancers must occur within a normal human lifespan, and genotypes detrimental to growth of the tumour as a whole may be selected. These factors may render invalid the classical model in which successive mutations with large advantages arise and spread through the tumour in selective sweeps. To incorporate these neglected features and to test how tumorigenesis depends on factors such as mutation rate, selection and size constraints, we shall set up a comprehensive model of tumour growth incorporating cell birth, death, division and mutation parameters. We shall examine specific aspects of cancer-as-evolution in mice. By marking mutant clones using fluorescent proteins, we can track them and see how they persist, spread and die. We shall also determine the mutation profiles and genetic diversity of mutant clones and whole tumours in mice and humans using next-generation sequencing. Specific experiments will determine: (i) the fate of new advantageous clones arising in an existing tumour; (ii) whether new disadvantageous clones can persist in tumours; (iii) whether apparently maladaptive traits for tumour growth, such as suppressing the growth of competitors, can be selected; (iv) why do housekeeper gene mutations cause cancer in specific sites; (v) can cancer cells have too much genomic instability; and (vi) whether all cancers develop owing to driver mutations with big effects, or are there “mini-drivers” of tumorigenesis? There will be continual cross-talk between the experimental and modelling work. The results of the project will enhance our basic understanding of tumorigenesis and suggest strategies for anticancer therapy."
Max ERC Funding
2 500 000 €
Duration
Start date: 2014-09-01, End date: 2019-08-31
Project acronym GOLNY
Project "German Operetta in London and New York, 1907–1939: Cultural Transfer and Transformation"
Researcher (PI) Derek B Scott
Host Institution (HI) UNIVERSITY OF LEEDS
Country United Kingdom
Call Details Advanced Grant (AdG), SH5, ERC-2013-ADG
Summary "The term ""German operetta"" in the project title embraces twentieth-century operettas originating in both Austria and Germany. These enjoyed remarkable success in London and New York during 1907–1937, and, without deeper knowledge of them and their audience reception, we are sadly lacking in our understanding of the cultural mainstream in early twentieth-century Austria, Germany, the UK, and USA. Surprisingly, there has been no rigorous scholarly study of the cultural transfer of these German operettas to Britain and the USA, despite its taking place in a period that can be demarcated clearly. Academic attention has focused, instead, on America’s influence on European stage works.
After Lehár’s Die lustige Witwe was produced to great acclaim in London and New York in 1907, the public appetite for German operetta grew rapidly in these cities. Although the First World War brought a temporary diminution of opportunities for new productions, there was an enthusiastic renewal of interest in the 1920s, and operettas from the theatres of Berlin were regularly adapted for the West End and Broadway. This project investigates the changes made for the London and New York productions in the context of cultural and social issues of the period, examining audience expectations, aspirations, and anxieties, and the social, cultural, and moral values of the times in which these works were created. It investigates how the operettas engage with modernity, innovative technology, social change, and cultural difference, seeking findings that will enhance knowledge of cultural transfer and transformation.
Recently, there have been encouraging signs of a new flowering of interest, as the music enters the public domain free from copyright restrictions. New publications offering digitized reprints of the vocal scores, and historic recordings of radio broadcasts are becoming available. This project will create new knowledge that will help to stimulate both academic and market interests."
Summary
"The term ""German operetta"" in the project title embraces twentieth-century operettas originating in both Austria and Germany. These enjoyed remarkable success in London and New York during 1907–1937, and, without deeper knowledge of them and their audience reception, we are sadly lacking in our understanding of the cultural mainstream in early twentieth-century Austria, Germany, the UK, and USA. Surprisingly, there has been no rigorous scholarly study of the cultural transfer of these German operettas to Britain and the USA, despite its taking place in a period that can be demarcated clearly. Academic attention has focused, instead, on America’s influence on European stage works.
After Lehár’s Die lustige Witwe was produced to great acclaim in London and New York in 1907, the public appetite for German operetta grew rapidly in these cities. Although the First World War brought a temporary diminution of opportunities for new productions, there was an enthusiastic renewal of interest in the 1920s, and operettas from the theatres of Berlin were regularly adapted for the West End and Broadway. This project investigates the changes made for the London and New York productions in the context of cultural and social issues of the period, examining audience expectations, aspirations, and anxieties, and the social, cultural, and moral values of the times in which these works were created. It investigates how the operettas engage with modernity, innovative technology, social change, and cultural difference, seeking findings that will enhance knowledge of cultural transfer and transformation.
Recently, there have been encouraging signs of a new flowering of interest, as the music enters the public domain free from copyright restrictions. New publications offering digitized reprints of the vocal scores, and historic recordings of radio broadcasts are becoming available. This project will create new knowledge that will help to stimulate both academic and market interests."
Max ERC Funding
1 061 762 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
