Project acronym 2SEXES_1GENOME
Project Sex-specific genetic effects on fitness and human disease
Researcher (PI) Edward Hugh Morrow
Host Institution (HI) THE UNIVERSITY OF SUSSEX
Call Details Starting Grant (StG), LS8, ERC-2011-StG_20101109
Summary Darwin’s theory of natural selection rests on the principle that fitness variation in natural populations has a heritable component, on which selection acts, thereby leading to evolutionary change. A fundamental and so far unresolved question for the field of evolutionary biology is to identify the genetic loci responsible for this fitness variation, thereby coming closer to an understanding of how variation is maintained in the face of continual selection. One important complicating factor in the search for fitness related genes however is the existence of separate sexes – theoretical expectations and empirical data both suggest that sexually antagonistic genes are common. The phrase “two sexes, one genome” nicely sums up the problem; selection may favour alleles in one sex, even if they have detrimental effects on the fitness of the opposite sex, since it is their net effect across both sexes that determine the likelihood that alleles persist in a population. This theoretical framework raises an interesting, and so far entirely unexplored issue: that in one sex the functional performance of some alleles is predicted to be compromised and this effect may account for some common human diseases and conditions which show genotype-sex interactions. I propose to explore the genetic basis of sex-specific fitness in a model organism in both laboratory and natural conditions and to test whether those genes identified as having sexually antagonistic effects can help explain the incidence of human diseases that display sexual dimorphism in prevalence, age of onset or severity. This multidisciplinary project directly addresses some fundamental unresolved questions in evolutionary biology: the genetic basis and maintenance of fitness variation; the evolution of sexual dimorphism; and aims to provide novel insights into the genetic basis of some common human diseases.
Summary
Darwin’s theory of natural selection rests on the principle that fitness variation in natural populations has a heritable component, on which selection acts, thereby leading to evolutionary change. A fundamental and so far unresolved question for the field of evolutionary biology is to identify the genetic loci responsible for this fitness variation, thereby coming closer to an understanding of how variation is maintained in the face of continual selection. One important complicating factor in the search for fitness related genes however is the existence of separate sexes – theoretical expectations and empirical data both suggest that sexually antagonistic genes are common. The phrase “two sexes, one genome” nicely sums up the problem; selection may favour alleles in one sex, even if they have detrimental effects on the fitness of the opposite sex, since it is their net effect across both sexes that determine the likelihood that alleles persist in a population. This theoretical framework raises an interesting, and so far entirely unexplored issue: that in one sex the functional performance of some alleles is predicted to be compromised and this effect may account for some common human diseases and conditions which show genotype-sex interactions. I propose to explore the genetic basis of sex-specific fitness in a model organism in both laboratory and natural conditions and to test whether those genes identified as having sexually antagonistic effects can help explain the incidence of human diseases that display sexual dimorphism in prevalence, age of onset or severity. This multidisciplinary project directly addresses some fundamental unresolved questions in evolutionary biology: the genetic basis and maintenance of fitness variation; the evolution of sexual dimorphism; and aims to provide novel insights into the genetic basis of some common human diseases.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym AMBH
Project Ancient Music Beyond Hellenisation
Researcher (PI) Stefan HAGEL
Host Institution (HI) OESTERREICHISCHE AKADEMIE DER WISSENSCHAFTEN
Call Details Advanced Grant (AdG), SH5, ERC-2017-ADG
Summary From medieval times, Arabic as well as European music was analysed in terms that were inherited from Classical Antiquity and had thus developed in a very different music culture. In spite of recent breakthroughs in the understanding of the latter, whose technicalities we access not only through texts and iconography, but also through instrument finds and surviving notated melodies, its relation to music traditions known from later periods and different places is almost uncharted territory.
The present project explores relations between Hellenic/Hellenistic music as pervaded the theatres and concert halls throughout and beyond the Roman empire, Near Eastern traditions – from the diatonic system emerging from cuneiform sources to the flourishing musical world of the caliphates – and, as far as possible, African musical life south of Egypt as well – a region that maintained close ties both with the Hellenised culture of its northern neighbours and with the Arabian Peninsula.
On the one hand, this demands collaboration between Classical Philology and Arabic Studies, extending methods recently developed within music archaeological research related to the Classical Mediterranean. Arabic writings need to be examined in close reading, using recent insights into the interplay between ancient music theory and practice, in order to segregate the influence of Greek thinking from ideas and facts that must relate to contemporaneous ‘Arabic’ music-making. In this way we hope better to define the relation of this tradition to the ‘Classical world’, potentially breaking free of Orientalising bias informing modern views. On the other hand, the study and reconstruction, virtual and material, of wind instruments of Hellenistic pedigree but found outside the confinements of the Hellenistic ‘heartlands’ may provide evidence of ‘foreign’ tonality employed in those regions – specifically the royal city of Meroë in modern Sudan and the Oxus Temple in modern Tajikistan.
Summary
From medieval times, Arabic as well as European music was analysed in terms that were inherited from Classical Antiquity and had thus developed in a very different music culture. In spite of recent breakthroughs in the understanding of the latter, whose technicalities we access not only through texts and iconography, but also through instrument finds and surviving notated melodies, its relation to music traditions known from later periods and different places is almost uncharted territory.
The present project explores relations between Hellenic/Hellenistic music as pervaded the theatres and concert halls throughout and beyond the Roman empire, Near Eastern traditions – from the diatonic system emerging from cuneiform sources to the flourishing musical world of the caliphates – and, as far as possible, African musical life south of Egypt as well – a region that maintained close ties both with the Hellenised culture of its northern neighbours and with the Arabian Peninsula.
On the one hand, this demands collaboration between Classical Philology and Arabic Studies, extending methods recently developed within music archaeological research related to the Classical Mediterranean. Arabic writings need to be examined in close reading, using recent insights into the interplay between ancient music theory and practice, in order to segregate the influence of Greek thinking from ideas and facts that must relate to contemporaneous ‘Arabic’ music-making. In this way we hope better to define the relation of this tradition to the ‘Classical world’, potentially breaking free of Orientalising bias informing modern views. On the other hand, the study and reconstruction, virtual and material, of wind instruments of Hellenistic pedigree but found outside the confinements of the Hellenistic ‘heartlands’ may provide evidence of ‘foreign’ tonality employed in those regions – specifically the royal city of Meroë in modern Sudan and the Oxus Temple in modern Tajikistan.
Max ERC Funding
775 959 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym ARCHADAPT
Project The architecture of adaptation to novel environments
Researcher (PI) Christian Werner Schlötterer
Host Institution (HI) VETERINAERMEDIZINISCHE UNIVERSITAET WIEN
Call Details Advanced Grant (AdG), LS8, ERC-2011-ADG_20110310
Summary One of the central goals in evolutionary biology is to understand adaptation. Experimental evolution represents a highly promising approach to study adaptation. In this proposal, a freshly collected D. simulans population will be allowed to adapt to laboratory conditions under two different temperature regimes: hot (27°C) and cold (18°C). The trajectories of adaptation to these novel environments will be monitored on three levels: 1) genomic, 2) transcriptomic, 3) phenotypic. Allele frequency changes during the experiment will be measured by next generation sequencing of DNA pools (Pool-Seq) to identify targets of selection. RNA-Seq will be used to trace adaptation on the transcriptomic level during three developmental stages. Eight different phenotypes will be scored to measure the phenotypic consequences of adaptation. Combining the adaptive trajectories on these three levels will provide a picture of adaptation for a multicellular, outcrossing organism that is far more detailed than any previous results.
Furthermore, the proposal addresses the question of how adaptation on these three levels is reversible if the environment reverts to ancestral conditions. The third aspect of adaptation covered in the proposal is the question of repeatability of adaptation. Again, this question will be addressed on the three levels: genomic, transcriptomic and phenotypic. Using replicates with different degrees of genetic similarity, as well as closely related species, we will test how similar the adaptive response is.
This large-scale study will provide new insights into the importance of standing variation for the adaptation to novel environments. Hence, apart from providing significant evolutionary insights on the trajectories of adaptation, the results we will obtain will have important implications for conservation genetics and commercial breeding.
Summary
One of the central goals in evolutionary biology is to understand adaptation. Experimental evolution represents a highly promising approach to study adaptation. In this proposal, a freshly collected D. simulans population will be allowed to adapt to laboratory conditions under two different temperature regimes: hot (27°C) and cold (18°C). The trajectories of adaptation to these novel environments will be monitored on three levels: 1) genomic, 2) transcriptomic, 3) phenotypic. Allele frequency changes during the experiment will be measured by next generation sequencing of DNA pools (Pool-Seq) to identify targets of selection. RNA-Seq will be used to trace adaptation on the transcriptomic level during three developmental stages. Eight different phenotypes will be scored to measure the phenotypic consequences of adaptation. Combining the adaptive trajectories on these three levels will provide a picture of adaptation for a multicellular, outcrossing organism that is far more detailed than any previous results.
Furthermore, the proposal addresses the question of how adaptation on these three levels is reversible if the environment reverts to ancestral conditions. The third aspect of adaptation covered in the proposal is the question of repeatability of adaptation. Again, this question will be addressed on the three levels: genomic, transcriptomic and phenotypic. Using replicates with different degrees of genetic similarity, as well as closely related species, we will test how similar the adaptive response is.
This large-scale study will provide new insights into the importance of standing variation for the adaptation to novel environments. Hence, apart from providing significant evolutionary insights on the trajectories of adaptation, the results we will obtain will have important implications for conservation genetics and commercial breeding.
Max ERC Funding
2 452 084 €
Duration
Start date: 2012-07-01, End date: 2018-06-30
Project acronym Biblant
Project The Bible and Antiquity in the 19th-Century
Researcher (PI) Simon Goldhill
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), SH5, ERC-2011-ADG_20110406
Summary This project will investigate the interface between the study of the bible and the study of antiquity in the nineteenth century. These two areas -- the bible and classics -- are central to the intellectual world of the 19th century, a source of knowledge, contention, and authority both as discrete topics, and, more importantly, in relation to and in competition with one another. It is impossible to understand Victorian society without appreciating the intellectual, social and institutional force of these concerns with the past. Yet modern disciplinary formation has not only separated them in the academy, but also marginalized both subject areas -- which has deeply attenuated comprehension of this foundational era. Our project will bring together scholars working on a range of fields including classics, history of education, cultural history, art history, literary history to bring back into view a fundamental but deeply misunderstood and underexplored aspect of the nineteenth century, which continues to have a significant impact on the contemporary world.
Summary
This project will investigate the interface between the study of the bible and the study of antiquity in the nineteenth century. These two areas -- the bible and classics -- are central to the intellectual world of the 19th century, a source of knowledge, contention, and authority both as discrete topics, and, more importantly, in relation to and in competition with one another. It is impossible to understand Victorian society without appreciating the intellectual, social and institutional force of these concerns with the past. Yet modern disciplinary formation has not only separated them in the academy, but also marginalized both subject areas -- which has deeply attenuated comprehension of this foundational era. Our project will bring together scholars working on a range of fields including classics, history of education, cultural history, art history, literary history to bring back into view a fundamental but deeply misunderstood and underexplored aspect of the nineteenth century, which continues to have a significant impact on the contemporary world.
Max ERC Funding
2 497 046 €
Duration
Start date: 2012-06-01, End date: 2017-05-31
Project acronym C-POS
Project Children's Palliative care Outcome Scale
Researcher (PI) RICHARD HARDING-SWALE
Host Institution (HI) KING'S COLLEGE LONDON
Call Details Consolidator Grant (CoG), LS7, ERC-2017-COG
Summary Person-centred care is a core health value of modern health care. The overarching aim of C-POS (Children's Palliative care Outcome Scale) is to develop and validate a person-centred outcome measure for children, young people (CYP) and their families affected by life-limiting & life-threatening conditions (LLLTC). International systematic reviews, and clinical guides have highlighted that currently none exists. This novel study will draw together a unique multidisciplinary collaboration to pioneer new methods, enabling engagement in outcome measurement by a population currently neglected in research.
C-POS builds on an international program of work. The sequential mixed methods will collect substantive data through objectives to determine i) the primary concerns of CYP and their families affected by LLLTC & preferences to enable participation in ethical person-centred measurement (n=50); ii) view of clinicians and commissioners on optimal implementation methods (national Delphi study); iii) a systematic review of current data collection tools for CYP regardless of condition; iv) integration of objectives i-iii to develop a tool (C-POS) with face and content validity; v) cognitive interviews to determine interpretability (n=40); vi) longitudinal cohort of CYP and families to determine test-retest reliability, internal consistency, construct validity and responsiveness (n=151); vii) development of resources for routine implementation viii) translation and interpretation protocols for international adoption.
C-POS is an ambitious study that, for the first time, will enable measurement of person-centred outcomes of care. This will be a turning point in the scientific study of a hitherto neglected group.
Summary
Person-centred care is a core health value of modern health care. The overarching aim of C-POS (Children's Palliative care Outcome Scale) is to develop and validate a person-centred outcome measure for children, young people (CYP) and their families affected by life-limiting & life-threatening conditions (LLLTC). International systematic reviews, and clinical guides have highlighted that currently none exists. This novel study will draw together a unique multidisciplinary collaboration to pioneer new methods, enabling engagement in outcome measurement by a population currently neglected in research.
C-POS builds on an international program of work. The sequential mixed methods will collect substantive data through objectives to determine i) the primary concerns of CYP and their families affected by LLLTC & preferences to enable participation in ethical person-centred measurement (n=50); ii) view of clinicians and commissioners on optimal implementation methods (national Delphi study); iii) a systematic review of current data collection tools for CYP regardless of condition; iv) integration of objectives i-iii to develop a tool (C-POS) with face and content validity; v) cognitive interviews to determine interpretability (n=40); vi) longitudinal cohort of CYP and families to determine test-retest reliability, internal consistency, construct validity and responsiveness (n=151); vii) development of resources for routine implementation viii) translation and interpretation protocols for international adoption.
C-POS is an ambitious study that, for the first time, will enable measurement of person-centred outcomes of care. This will be a turning point in the scientific study of a hitherto neglected group.
Max ERC Funding
1 799 820 €
Duration
Start date: 2018-09-01, End date: 2023-02-28
Project acronym CANCERINNOVATION
Project Using novel methodologies to target and image cancer invasion and therapeutic resistance
Researcher (PI) Margaret Frame
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Advanced Grant (AdG), LS7, ERC-2011-ADG_20110310
Summary We aim to develop and apply a suite of new technologies in a novel cancer discovery platform that will link high-definition cancer biology, via state-of-the-art disease imaging and pathway modelling, with development of novel interrogative and therapeutic interventions to test in models of cancer that closely resemble human disease. The work will lead to a new understanding of cancer invasion, how to treat advanced disease in the metastatic niche, how to monitor therapeutic responses and the compensatory mechanisms that cause acquired resistance. Platform development will be based on combined, cross-informing technologies that will enable us to predict optimal ‘maintenance therapies’ for metastatic disease by targeting cancer evolution and spread through combination therapy. A key strand of the platform is the development of quantitative multi-modal imaging in vivo by use of optical window technology to inform detailed understanding of disease and drug mechanisms and predictive capability of pathway biomarkers. Innovative methodologies are urgently needed to address declining approval rates of novel medicines and the unmet clinical needs of treating cancer patients in the advanced disease setting, where tumour spread and survival generally continues unchecked by current therapies. This work will be largely pre-clinical, but will always be mindful of the clinical problem in managing late stage human disease through rationale design of combination therapies with companion diagnostic tests. The cancer survival statistics will be changed if we can curb continuing spread of aggressive, metastatic disease and resistance to therapy by taking smarter combined approaches that make best use of emerging technologies in an innovative way, particularly where they are more predictive of clinical efficacy.
Summary
We aim to develop and apply a suite of new technologies in a novel cancer discovery platform that will link high-definition cancer biology, via state-of-the-art disease imaging and pathway modelling, with development of novel interrogative and therapeutic interventions to test in models of cancer that closely resemble human disease. The work will lead to a new understanding of cancer invasion, how to treat advanced disease in the metastatic niche, how to monitor therapeutic responses and the compensatory mechanisms that cause acquired resistance. Platform development will be based on combined, cross-informing technologies that will enable us to predict optimal ‘maintenance therapies’ for metastatic disease by targeting cancer evolution and spread through combination therapy. A key strand of the platform is the development of quantitative multi-modal imaging in vivo by use of optical window technology to inform detailed understanding of disease and drug mechanisms and predictive capability of pathway biomarkers. Innovative methodologies are urgently needed to address declining approval rates of novel medicines and the unmet clinical needs of treating cancer patients in the advanced disease setting, where tumour spread and survival generally continues unchecked by current therapies. This work will be largely pre-clinical, but will always be mindful of the clinical problem in managing late stage human disease through rationale design of combination therapies with companion diagnostic tests. The cancer survival statistics will be changed if we can curb continuing spread of aggressive, metastatic disease and resistance to therapy by taking smarter combined approaches that make best use of emerging technologies in an innovative way, particularly where they are more predictive of clinical efficacy.
Max ERC Funding
2 499 000 €
Duration
Start date: 2012-08-01, End date: 2017-07-31
Project acronym CATENA
Project Commentary Manuscripts in the History and Transmission of the Greek New Testament
Researcher (PI) HUGH ALEXANDER GERVASE HOUGHTON
Host Institution (HI) THE UNIVERSITY OF BIRMINGHAM
Call Details Consolidator Grant (CoG), SH5, ERC-2017-COG
Summary Manuscripts which contain commentary alongside the biblical text are some of the most significant and complicated witnesses to the Greek New Testament. First compiled around the fifth century, the commentaries consist of chains of extracts from earlier writers (catenae). These manuscripts became the main way in which users encountered both the text and the interpretation of the New Testament; revised editions produced in the eleventh and twelfth centuries continued to hold the field until the invention of printing.
Recent advances have shown that commentary manuscripts play a much more important role than previously thought in the history of the New Testament. The number of known copies has increased by 20% following a preliminary survey last year which identified 100 additional manuscripts. A recent comprehensive textual analysis of the Catholic Epistles indicated that all witnesses from the third generation onwards (some 72% of the total) could stem from the biblical text of three commentary manuscripts occupying a key place in the textual tradition. Investigation of the catena on Mark has shown that the selection of extracts could offer a new approach to understanding the theology of the compilers and the transmission of the commentaries.
The CATENA Project will use digital tools to undertake a fuller examination of Greek New Testament commentary manuscripts than has ever before been possible. This will include an exhaustive survey to establish a complete list of witnesses; a database of extracts to examine their principles of organisation and relationships; and electronic transcriptions to determine their role in the transmission of the biblical text. The results will have a direct impact on editions of the Greek New Testament, providing a new understanding of its text and reception and leading to broader insights into history and culture.
Summary
Manuscripts which contain commentary alongside the biblical text are some of the most significant and complicated witnesses to the Greek New Testament. First compiled around the fifth century, the commentaries consist of chains of extracts from earlier writers (catenae). These manuscripts became the main way in which users encountered both the text and the interpretation of the New Testament; revised editions produced in the eleventh and twelfth centuries continued to hold the field until the invention of printing.
Recent advances have shown that commentary manuscripts play a much more important role than previously thought in the history of the New Testament. The number of known copies has increased by 20% following a preliminary survey last year which identified 100 additional manuscripts. A recent comprehensive textual analysis of the Catholic Epistles indicated that all witnesses from the third generation onwards (some 72% of the total) could stem from the biblical text of three commentary manuscripts occupying a key place in the textual tradition. Investigation of the catena on Mark has shown that the selection of extracts could offer a new approach to understanding the theology of the compilers and the transmission of the commentaries.
The CATENA Project will use digital tools to undertake a fuller examination of Greek New Testament commentary manuscripts than has ever before been possible. This will include an exhaustive survey to establish a complete list of witnesses; a database of extracts to examine their principles of organisation and relationships; and electronic transcriptions to determine their role in the transmission of the biblical text. The results will have a direct impact on editions of the Greek New Testament, providing a new understanding of its text and reception and leading to broader insights into history and culture.
Max ERC Funding
1 756 928 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym CHARTING THE DIGITAL
Project Charting the Digital: Digital Mapping Practices as New Media Cultures
Researcher (PI) Sybille Lammes
Host Institution (HI) THE UNIVERSITY OF WARWICK
Call Details Starting Grant (StG), SH5, ERC-2011-StG_20101124
Summary Maps have changed and with that our sense of space and spatial awareness. The key objective of this research programme is to develop a framework for the conceptualization of digital maps as new techno-cultural phenomena. Digital maps allow a greater degree of interaction between users and mapping interfaces than analogue maps do. Instead of just reading maps, users have far more influence on how maps look. Whether a navigation device that adjusts its route-display according to where the driver chooses to go, or a map in a computer-game that is partly created by players, maps have become more interactive and are now co-produced by their users.
With this ERC starting grant I propose to build up a new research programme to investigate what this shift entails. I will do so by conducting a comparative analysis of a broad spectrum of digital mapping devices: in relation to (a) each other, (b) traditional cartography and (c) to other media forms that are concerned with mapping and navigation.
This research programme will yield new results on how digital maps can be simultaneously understood as new media, technologies and cartographies by using a unique combination of perspectives from New Media Studies, Science and Technologies Studies. It will also contribute to a recently emerging discussion in which new media are conceived as material cultures that are physically embedded in daily life, countering conventional views of them as just new, virtual and ‘out there’. Digital maps underscore all the main assertions that figure in this recent ‘material turn’ at once: they remediate existing spaces, they merge virtual and physical spaces and are locally used and appropriated yet at the same time products of a global culture. This study will thus break new ground by offering New Media Studies innovative ways for understanding materiality, spatiality and technology.
Summary
Maps have changed and with that our sense of space and spatial awareness. The key objective of this research programme is to develop a framework for the conceptualization of digital maps as new techno-cultural phenomena. Digital maps allow a greater degree of interaction between users and mapping interfaces than analogue maps do. Instead of just reading maps, users have far more influence on how maps look. Whether a navigation device that adjusts its route-display according to where the driver chooses to go, or a map in a computer-game that is partly created by players, maps have become more interactive and are now co-produced by their users.
With this ERC starting grant I propose to build up a new research programme to investigate what this shift entails. I will do so by conducting a comparative analysis of a broad spectrum of digital mapping devices: in relation to (a) each other, (b) traditional cartography and (c) to other media forms that are concerned with mapping and navigation.
This research programme will yield new results on how digital maps can be simultaneously understood as new media, technologies and cartographies by using a unique combination of perspectives from New Media Studies, Science and Technologies Studies. It will also contribute to a recently emerging discussion in which new media are conceived as material cultures that are physically embedded in daily life, countering conventional views of them as just new, virtual and ‘out there’. Digital maps underscore all the main assertions that figure in this recent ‘material turn’ at once: they remediate existing spaces, they merge virtual and physical spaces and are locally used and appropriated yet at the same time products of a global culture. This study will thus break new ground by offering New Media Studies innovative ways for understanding materiality, spatiality and technology.
Max ERC Funding
1 422 453 €
Duration
Start date: 2011-11-01, End date: 2016-10-31
Project acronym COMPAUL
Project The Earliest Commentaries on Paul as Sources for the Biblical Text
Researcher (PI) Hugh Alexander Gervase Houghton
Host Institution (HI) THE UNIVERSITY OF BIRMINGHAM
Call Details Starting Grant (StG), SH5, ERC-2011-StG_20101124
Summary This project will develop a new approach to the textual history of the Pauline Epistles by exploring the biblical text of the earliest commentaries in Greek and Latin. Each author's treatment of their source gives insights into their compositional practices, their attitudes to the Bible and the differing versions of the New Testament known to them. Detailed verbal analysis of the quotations will identify the form of text originally used and situate it within the wider textual tradition. Studying the subsequent transmission of these commentaries in their manuscripts and in other writers will reveal how they were altered or adapted to bring them into agreement with later textual norms and practices. It will also show the development of a hierarchy of authority, first for the biblical and then for the authorial text. The methodology pioneered by the project offers a new paradigm for using biblical quotations and Christian writers to reconstruct early forms of the New Testament text.
Summary
This project will develop a new approach to the textual history of the Pauline Epistles by exploring the biblical text of the earliest commentaries in Greek and Latin. Each author's treatment of their source gives insights into their compositional practices, their attitudes to the Bible and the differing versions of the New Testament known to them. Detailed verbal analysis of the quotations will identify the form of text originally used and situate it within the wider textual tradition. Studying the subsequent transmission of these commentaries in their manuscripts and in other writers will reveal how they were altered or adapted to bring them into agreement with later textual norms and practices. It will also show the development of a hierarchy of authority, first for the biblical and then for the authorial text. The methodology pioneered by the project offers a new paradigm for using biblical quotations and Christian writers to reconstruct early forms of the New Testament text.
Max ERC Funding
1 499 233 €
Duration
Start date: 2011-10-01, End date: 2016-09-30
Project acronym DROSOPHILAINFECTION
Project Genetic variation in the susceptibility of Drosophila to infection
Researcher (PI) Francis Michael Jiggins
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS8, ERC-2011-StG_20101109
Summary Insects vary in their susceptibility to viral infection, and this variation affects disease transmission by vectors and the survival of beneficial insects. Identifying the genes that cause this variation will provide insights into both the molecular interactions between insects and their parasites, and the processes that maintain this variation in populations. We propose to do this in Drosophila, where genome-wide association studies are now possible thanks to the publication of large numbers of genome sequences. Furthermore, new techniques allow the sequence of Drosophila genes to be precisely altered, which will allow the exact molecular changes affecting resistance to be confirmed experimentally. Using these powerful techniques, we will first identify genes that affect resistance to a diverse panel of different viruses, which will allow us to understand the molecular and cellular basis of how resistance to different groups of viruses evolves in nature. Next, we will repeat this analysis using different isolates of the same virus, to identify the molecular basis of the ‘specific’ resistance commonly observed in invertebrates, where different host genotypes are resistant to different parasite genotypes. Once we have identified the polymorphisms that affect resistance, we can then use these results to examine the evolutionary processes that maintain this variation in populations: are alleles that increase resistance costly, how has natural selection acted on the polymorphisms, and is there more variation if the virus has naturally coevolved with Drosophila than if the virus was isolated from another insect. Finally, by hybridising D. melanogaster to D. simulans, we will extend these experiments to identify genes that cause species to differ in resistance, which will reveal the molecular basis of how resistance evolves over millions of years and how viruses adapt to their hosts.
Summary
Insects vary in their susceptibility to viral infection, and this variation affects disease transmission by vectors and the survival of beneficial insects. Identifying the genes that cause this variation will provide insights into both the molecular interactions between insects and their parasites, and the processes that maintain this variation in populations. We propose to do this in Drosophila, where genome-wide association studies are now possible thanks to the publication of large numbers of genome sequences. Furthermore, new techniques allow the sequence of Drosophila genes to be precisely altered, which will allow the exact molecular changes affecting resistance to be confirmed experimentally. Using these powerful techniques, we will first identify genes that affect resistance to a diverse panel of different viruses, which will allow us to understand the molecular and cellular basis of how resistance to different groups of viruses evolves in nature. Next, we will repeat this analysis using different isolates of the same virus, to identify the molecular basis of the ‘specific’ resistance commonly observed in invertebrates, where different host genotypes are resistant to different parasite genotypes. Once we have identified the polymorphisms that affect resistance, we can then use these results to examine the evolutionary processes that maintain this variation in populations: are alleles that increase resistance costly, how has natural selection acted on the polymorphisms, and is there more variation if the virus has naturally coevolved with Drosophila than if the virus was isolated from another insect. Finally, by hybridising D. melanogaster to D. simulans, we will extend these experiments to identify genes that cause species to differ in resistance, which will reveal the molecular basis of how resistance evolves over millions of years and how viruses adapt to their hosts.
Max ERC Funding
1 498 072 €
Duration
Start date: 2011-11-01, End date: 2017-10-31