Project acronym DNATRAFFIC
Project DNA traffic during bacterial cell division
Researcher (PI) François-Xavier Andre Fernand Barre
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS1, ERC-2011-StG_20101109
Summary The molecular mechanisms that serve to couple DNA replication, chromosome segregation and cell division are largely unknown in bacteria. This led a considerable interest to the study of Escherichia coli FtsK, an essential cell division protein that assembles into DNA-pumps to transfer chromosomal DNA between the two daughter cell compartments during septation. Indeed, our recent work suggests that FtsK might regulate the late stages of septation to ensure DNA is fully cleared from the septum before it is allowed to close. This would be the first example of a cell cycle checkpoint in bacteria.
FtsK-mediated DNA transfer is required in 15% of the cells at each generation in E. coli, in which it serves to promote the resolution of topological problems arising from the circularity of the chromosome by Xer recombination. However, the FtsK checkpoint could be a more general feature of the bacterial cell cycle since FtsK is highly conserved among eubacteria, including species that do not possess a Xer system. Indeed, preliminary results from the lab indicate that DNA transfer by FtsK is required independently of Xer recombination in Vibrio cholerae.
To confirm the existence and the generality of the FtsK checkpoint in bacteria, we will determine the different situations that lead to a requirement for FtsK-mediated DNA transfer by studying chromosome segregation and cell division in V. cholerae. In parallel, we will apply new fluorescent microscopy tools to follow the progression of cell division and chromosome segregation in single live bacterial cells. PALM will notably serve to probe the structure of the FtsK DNA-pumps at a high spatial resolution, FRET will be used to determine their timing of assembly and their interactions with the other cell division proteins, and TIRF will serve to follow in real time their activity with respect to the progression of chromosome dimer resolution, chromosome segregation, and septum closure.
Summary
The molecular mechanisms that serve to couple DNA replication, chromosome segregation and cell division are largely unknown in bacteria. This led a considerable interest to the study of Escherichia coli FtsK, an essential cell division protein that assembles into DNA-pumps to transfer chromosomal DNA between the two daughter cell compartments during septation. Indeed, our recent work suggests that FtsK might regulate the late stages of septation to ensure DNA is fully cleared from the septum before it is allowed to close. This would be the first example of a cell cycle checkpoint in bacteria.
FtsK-mediated DNA transfer is required in 15% of the cells at each generation in E. coli, in which it serves to promote the resolution of topological problems arising from the circularity of the chromosome by Xer recombination. However, the FtsK checkpoint could be a more general feature of the bacterial cell cycle since FtsK is highly conserved among eubacteria, including species that do not possess a Xer system. Indeed, preliminary results from the lab indicate that DNA transfer by FtsK is required independently of Xer recombination in Vibrio cholerae.
To confirm the existence and the generality of the FtsK checkpoint in bacteria, we will determine the different situations that lead to a requirement for FtsK-mediated DNA transfer by studying chromosome segregation and cell division in V. cholerae. In parallel, we will apply new fluorescent microscopy tools to follow the progression of cell division and chromosome segregation in single live bacterial cells. PALM will notably serve to probe the structure of the FtsK DNA-pumps at a high spatial resolution, FRET will be used to determine their timing of assembly and their interactions with the other cell division proteins, and TIRF will serve to follow in real time their activity with respect to the progression of chromosome dimer resolution, chromosome segregation, and septum closure.
Max ERC Funding
1 565 938 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym DYMOCHRO
Project Dynamics of modified chromatin domains
Researcher (PI) Fabian, Roman ERDEL
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS1, ERC-2018-STG
Summary Cellular identity is defined by complex patterns of DNA and histone modifications, which partition our chromosomes and determine how cells interpret the genetic information. For cells to remember who they are, these modifications have to be tightly regulated over time and through cell division. Loss of cellular identity promotes different types of disease including neurological disorders and cancer.
Histone modifications can spread along chromatin and can be transmitted through cell division, giving rise to chromatin position effects and cellular memory. However, the underlying molecular mechanisms are not understood. In particular, we do not know how the size and stability of modified domains is controlled, and we currently lack techniques to study these processes in real-time.
Here, I propose to develop the single-molecule ‘chromatin curtains’ platform to directly visualize spreading and maintenance of histone methylation in a reconstituted system and to compare the resulting domains to those found on individual chromatin fibers isolated from cells. In a complementary approach, I will devise and set up a tunable synthetic circuit that installs and reinforces orthogonal epigenetic modifications in living cells to define the functional modules that are necessary and sufficient for chromatin position effects and cellular memory.
My project combines molecular biophysics with synthetic biology to elucidate the fundamental principles that govern the dynamics of histone modifications to establish and preserve cellular identity. The chromatin curtains platform I will develop complements sequencing-based methods and will make it for the first time possible to directly assess the dynamics of histone modification patterns on single chromatin fibers under native conditions. I anticipate that the insights gained in my project will aid in the design of future strategies to control histone modifications in disease.
Summary
Cellular identity is defined by complex patterns of DNA and histone modifications, which partition our chromosomes and determine how cells interpret the genetic information. For cells to remember who they are, these modifications have to be tightly regulated over time and through cell division. Loss of cellular identity promotes different types of disease including neurological disorders and cancer.
Histone modifications can spread along chromatin and can be transmitted through cell division, giving rise to chromatin position effects and cellular memory. However, the underlying molecular mechanisms are not understood. In particular, we do not know how the size and stability of modified domains is controlled, and we currently lack techniques to study these processes in real-time.
Here, I propose to develop the single-molecule ‘chromatin curtains’ platform to directly visualize spreading and maintenance of histone methylation in a reconstituted system and to compare the resulting domains to those found on individual chromatin fibers isolated from cells. In a complementary approach, I will devise and set up a tunable synthetic circuit that installs and reinforces orthogonal epigenetic modifications in living cells to define the functional modules that are necessary and sufficient for chromatin position effects and cellular memory.
My project combines molecular biophysics with synthetic biology to elucidate the fundamental principles that govern the dynamics of histone modifications to establish and preserve cellular identity. The chromatin curtains platform I will develop complements sequencing-based methods and will make it for the first time possible to directly assess the dynamics of histone modification patterns on single chromatin fibers under native conditions. I anticipate that the insights gained in my project will aid in the design of future strategies to control histone modifications in disease.
Max ERC Funding
1 447 860 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym FUTUREPOL
Project A Political History of the Future : Knowledge Production and Future Governance 1945-2010
Researcher (PI) Jenny Andersson
Host Institution (HI) FONDATION NATIONALE DES SCIENCES POLITIQUES
Call Details Starting Grant (StG), SH2, ERC-2011-StG_20101124
Summary FUTUREPOL seeks to open up a new field of historical and political enquiry around the history of future governance. As an object of governance, the future is notoriously rebellious: difficult to define, defying notions of objectivity and truth. Nevertheless, a crucial feature of modern societies is their belief in the knowability and governability of the future, the belief that through the means of scientific rationality and political power, the future can be controlled. FUTUREPOL aims to study shifting ideas of the knowability and governability of the future, in order to illuminate the process in which the future is transformed from its nebulous and uncertain state into an object of governance. Moreover, it intends an historical analysis of how this process varies over time in the post war period. The project thus asks two central research questions: How does the future become an object of governance? And how is this process different today, than earlier in the post war period? FUTUREPOL will address four problems: First, it will study the origins of futurology and its birth in transnational networks of futurists in the immediate post war period. Second, it intends to study the way that futurists’ ideas were translated into policy and gave rise to public institutions devoted to the future in many countries in Europe and beyond. Third, it will situate these problems in a global field where concerns with national futures are confronted to concerns with the survival of the world system as a whole, and fourth, it aims to study the evolution of the means of future governance over time, and proposes that such an historical analysis of future governance can permit us to historicize central forms of modern governance such as the governance of risk, foresight or scenarios, and thus help us understand the way that contemporary societies engage with the future.
Summary
FUTUREPOL seeks to open up a new field of historical and political enquiry around the history of future governance. As an object of governance, the future is notoriously rebellious: difficult to define, defying notions of objectivity and truth. Nevertheless, a crucial feature of modern societies is their belief in the knowability and governability of the future, the belief that through the means of scientific rationality and political power, the future can be controlled. FUTUREPOL aims to study shifting ideas of the knowability and governability of the future, in order to illuminate the process in which the future is transformed from its nebulous and uncertain state into an object of governance. Moreover, it intends an historical analysis of how this process varies over time in the post war period. The project thus asks two central research questions: How does the future become an object of governance? And how is this process different today, than earlier in the post war period? FUTUREPOL will address four problems: First, it will study the origins of futurology and its birth in transnational networks of futurists in the immediate post war period. Second, it intends to study the way that futurists’ ideas were translated into policy and gave rise to public institutions devoted to the future in many countries in Europe and beyond. Third, it will situate these problems in a global field where concerns with national futures are confronted to concerns with the survival of the world system as a whole, and fourth, it aims to study the evolution of the means of future governance over time, and proposes that such an historical analysis of future governance can permit us to historicize central forms of modern governance such as the governance of risk, foresight or scenarios, and thus help us understand the way that contemporary societies engage with the future.
Max ERC Funding
1 302 949 €
Duration
Start date: 2012-01-01, End date: 2017-09-30
Project acronym GENOCIDE
Project Corpses of Genocide and Mass Violence: Interdisciplinary and Comparative Approaches of Dead Bodies Treatment in the 20th Century (Destruction, Identification, Reconciliation)
Researcher (PI) Elisabeth Gessat Anstett
Host Institution (HI) ECOLE DES HAUTES ETUDES EN SCIENCES SOCIALES
Call Details Starting Grant (StG), SH2, ERC-2011-StG_20101124
Summary In Europe and all over the world, genocide and mass violence have been a structural feature of the 20th century. This project aims at questioning the social legacy of mass violence by studying how different societies have coped with the first consequence of mass destruction: the mass production of cadavers. What status and what value have indeed been given to corpses? What political, social or religious uses have been made of dead bodies in occupied Europe, Soviet Union, Serbia, Spain but also Rwanda, Argentina or Cambodia, both during and after the massacres? Bringing together perspectives of social anthropology, history and law, and raising the three main issues of destruction, identification and reconciliation, our project will enlighten how various social and cultural treatments of dead bodies simultaneously challenge common representations, legal practices and moral. Project outputs will therefore open and strengthen the field of genocide studies by providing proper intellectual and theoretical tools for a better understanding of mass violence’s aftermaths in today societies.
Summary
In Europe and all over the world, genocide and mass violence have been a structural feature of the 20th century. This project aims at questioning the social legacy of mass violence by studying how different societies have coped with the first consequence of mass destruction: the mass production of cadavers. What status and what value have indeed been given to corpses? What political, social or religious uses have been made of dead bodies in occupied Europe, Soviet Union, Serbia, Spain but also Rwanda, Argentina or Cambodia, both during and after the massacres? Bringing together perspectives of social anthropology, history and law, and raising the three main issues of destruction, identification and reconciliation, our project will enlighten how various social and cultural treatments of dead bodies simultaneously challenge common representations, legal practices and moral. Project outputs will therefore open and strengthen the field of genocide studies by providing proper intellectual and theoretical tools for a better understanding of mass violence’s aftermaths in today societies.
Max ERC Funding
1 197 367 €
Duration
Start date: 2012-02-01, End date: 2016-01-31
Project acronym KHAM
Project Territories, Communities and Exchanges in the Sino-Tibetan Kham Borderlands (China)
Researcher (PI) Stéphane Gros
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), SH2, ERC-2011-StG_20101124
Summary This research project will focus on the area of the Sino-Tibetan borderlands situated within the People’s Republic of China, and referred to as Kham by Tibetans who make up most of the population of this region divided between the provinces of Sichuan to the east, Yunnan to the south and the Tibet Autonomous Region to the west. This research project intends to explore from a comparative perspective the possible definitions of this entity called Kham, which in the course of history has never strictly corresponded to any administrative unit or coherent whole, and which ultimately should be considered as a land of encounters, a place of métissage (cultural exchanges).
By addressing a regional area virtually overlooked by Western research in social science, this project aims to strengthen international academic exchanges and to produce a strong network of collaboration on Kham studies. The multidisciplinary team will undertake ethnographic field studies and documentary research including archival research and contribute fresh, first-hand material to the socio-cultural diversity of Kham.
In-depth investigation of the internal diversity of Tibet and its connection with the outside remains sketchy and thus a particular focus of this project is to delve into the complexities of Tibetan society in China. This pioneering work will provide new materials on four complementary cross-disciplinary themes: 1) trade and commerce, 2) ethnicity, religion and local identities, 3) political entities and social organization, and 4) representations and cultural politics, each of which in its own way will improve our understanding of the particular historical, social and political context of the Kham region. Finally, this multi-tiered and multi-scalar approach, with an emphasis on networks, will enhance work on historical mapping, which is still practically non-existent in this region.
Summary
This research project will focus on the area of the Sino-Tibetan borderlands situated within the People’s Republic of China, and referred to as Kham by Tibetans who make up most of the population of this region divided between the provinces of Sichuan to the east, Yunnan to the south and the Tibet Autonomous Region to the west. This research project intends to explore from a comparative perspective the possible definitions of this entity called Kham, which in the course of history has never strictly corresponded to any administrative unit or coherent whole, and which ultimately should be considered as a land of encounters, a place of métissage (cultural exchanges).
By addressing a regional area virtually overlooked by Western research in social science, this project aims to strengthen international academic exchanges and to produce a strong network of collaboration on Kham studies. The multidisciplinary team will undertake ethnographic field studies and documentary research including archival research and contribute fresh, first-hand material to the socio-cultural diversity of Kham.
In-depth investigation of the internal diversity of Tibet and its connection with the outside remains sketchy and thus a particular focus of this project is to delve into the complexities of Tibetan society in China. This pioneering work will provide new materials on four complementary cross-disciplinary themes: 1) trade and commerce, 2) ethnicity, religion and local identities, 3) political entities and social organization, and 4) representations and cultural politics, each of which in its own way will improve our understanding of the particular historical, social and political context of the Kham region. Finally, this multi-tiered and multi-scalar approach, with an emphasis on networks, will enhance work on historical mapping, which is still practically non-existent in this region.
Max ERC Funding
651 722 €
Duration
Start date: 2012-03-01, End date: 2016-02-29
Project acronym MOLSTRUCTTRANSFO
Project Molecular and Structural Biology of Bacterial Transformation
Researcher (PI) Rémi Fronzes
Host Institution (HI) INSTITUT PASTEUR
Call Details Starting Grant (StG), LS1, ERC-2011-StG_20101109
Summary A common form of gene transfer is the vertical gene transfer between one organism and its offspring during sexual reproduction. However, some organisms, such as bacteria, are able to acquire genetic material independently of sexual reproduction by horizontal gene transfer (HGT). Three mechanisms mediate HGT in bacteria: conjugation, transduction and natural transformation. HGT and the selective pressure exerted by the widespread use antibiotics (in medicine, veterinary medicine, agriculture, animal feeding, etc) are responsible for the rapid spread of antibiotic resistance genes among pathogenic bacteria.
In this proposal, we focus on bacterial transformation systems, also named competence systems. Natural transformation is the acquisition of naked DNA from the extracellular milieu. It is the only programmed process for generalized genetic exchange found in bacteria. This highly efficient and regulated process promotes bacterial genome plasticity and adaptive response of bacteria to changes in their environment. It is essential for bacterial survival and/or virulence and greatly limits efficiency of treatments or vaccine against some pathogenic bacteria.
The architecture and functioning of the membrane protein complexes mediating DNA transfer through the cell envelope during bacterial transformation remain elusive. We want to decipher the molecular mechanism of this transfer. To attain this goal, we will carry out structural biology studies (X-ray crystallography and high resolution electron microscopy) as well as functional and structure-function in vivo studies. We have the ambition to make major contributions to the understanding of bacterial transformation. Ultimately, we hope that our results will also help to find compounds that could block natural transformation in bacterial pathogens.
Summary
A common form of gene transfer is the vertical gene transfer between one organism and its offspring during sexual reproduction. However, some organisms, such as bacteria, are able to acquire genetic material independently of sexual reproduction by horizontal gene transfer (HGT). Three mechanisms mediate HGT in bacteria: conjugation, transduction and natural transformation. HGT and the selective pressure exerted by the widespread use antibiotics (in medicine, veterinary medicine, agriculture, animal feeding, etc) are responsible for the rapid spread of antibiotic resistance genes among pathogenic bacteria.
In this proposal, we focus on bacterial transformation systems, also named competence systems. Natural transformation is the acquisition of naked DNA from the extracellular milieu. It is the only programmed process for generalized genetic exchange found in bacteria. This highly efficient and regulated process promotes bacterial genome plasticity and adaptive response of bacteria to changes in their environment. It is essential for bacterial survival and/or virulence and greatly limits efficiency of treatments or vaccine against some pathogenic bacteria.
The architecture and functioning of the membrane protein complexes mediating DNA transfer through the cell envelope during bacterial transformation remain elusive. We want to decipher the molecular mechanism of this transfer. To attain this goal, we will carry out structural biology studies (X-ray crystallography and high resolution electron microscopy) as well as functional and structure-function in vivo studies. We have the ambition to make major contributions to the understanding of bacterial transformation. Ultimately, we hope that our results will also help to find compounds that could block natural transformation in bacterial pathogens.
Max ERC Funding
1 405 149 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym MultiMotif
Project Motif repeats in intrinsically disordered regions of the clathrin mediated endocytosis pathway
Researcher (PI) Sigrid MILLES
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS1, ERC-2018-STG
Summary Linear motifs are short sequence stretches that occur in intrinsically disordered protein regions (IDRs) lacking stable secondary and tertiary structure, and mediate vital interactions within various biological systems. An exemplary system for the presence of IDRs and a high concentration of linear motifs is the clathrin mediated endocytosis machinery of the eukaryotic cell, where a complex interaction network of IDR-rich adaptor proteins enables both protein and lipid interactions. The molecular mechanism of such interactions, especially when multiple motifs act in concert, is however only poorly understood particularly since the dynamic and flexible nature of IDRs makes them a very difficult object to study. I aim to develop an integrative approach based on single molecule fluorescence and NMR spectroscopies to characterize the molecular principles of IDRs in clathrin mediated endocytosis. A systematic analysis of IDRs with different types of motifs and various interaction partners will not only shed light on the molecular functions of linear motifs within endocytosis, but also on how multiplicities of linear motifs may work in various biological processes in general. In vitro structural studies will be connected with single molecule imaging to relate molecular conformation with function within the cell.
Summary
Linear motifs are short sequence stretches that occur in intrinsically disordered protein regions (IDRs) lacking stable secondary and tertiary structure, and mediate vital interactions within various biological systems. An exemplary system for the presence of IDRs and a high concentration of linear motifs is the clathrin mediated endocytosis machinery of the eukaryotic cell, where a complex interaction network of IDR-rich adaptor proteins enables both protein and lipid interactions. The molecular mechanism of such interactions, especially when multiple motifs act in concert, is however only poorly understood particularly since the dynamic and flexible nature of IDRs makes them a very difficult object to study. I aim to develop an integrative approach based on single molecule fluorescence and NMR spectroscopies to characterize the molecular principles of IDRs in clathrin mediated endocytosis. A systematic analysis of IDRs with different types of motifs and various interaction partners will not only shed light on the molecular functions of linear motifs within endocytosis, but also on how multiplicities of linear motifs may work in various biological processes in general. In vitro structural studies will be connected with single molecule imaging to relate molecular conformation with function within the cell.
Max ERC Funding
1 599 809 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym NDOGS
Project Nuclear Dynamic, Organization and Genome Stability
Researcher (PI) Karine Marie Renée Dubrana
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Call Details Starting Grant (StG), LS1, ERC-2011-StG_20101109
Summary The eukaryotic genome is packaged into large-scale chromatin structures occupying distinct domains in the cell nucleus. Nuclear compartmentalization has recently been proposed to play an important role in genome stability but the molecular steps regulated remain to be defined. Focusing on Double strand breaks (DSBs) in response to which cells activate checkpoint and DNA repair pathways, we propose to characterize the spatial and temporal behavior of damaged chromatin and determine how this affects the maintenance of genome integrity. Currently, most studies concerning DSBs signaling and repair have been realized on asynchronous cell populations, which makes it difficult to precisely define the kinetics of events that occur at the cellular level. We thus propose to follow the nuclear localization and dynamics of an inducible DSB concomitantly with the kinetics of checkpoint activation and DNA repair at a single cell level and along the cell cycle. This will be performed using budding yeast as a model system enabling the combination of genetics, molecular biology and advanced live microscopy. We recently demonstrated that DSBs relocated to the nuclear periphery where they contact nuclear pores. This change in localization possibly regulates the choice of the repair pathway through steps that are controlled by post-translational modifications. This proposal aims at dissecting the molecular pathways defining the position of DSBs in the nucleus by performing genetic and proteomic screens, testing the functional consequence of nuclear position for checkpoint activation and DNA repair by driving the DSB to specific nuclear landmarks and, defining the dynamics of DNA damages in different repair contexts. Our project will identify new players in the DNA repair and checkpoint pathways and further our understanding of how the compartmentalization of damaged chromatin into the nucleus regulates these processes to insure the transmission of a stable genome.
Summary
The eukaryotic genome is packaged into large-scale chromatin structures occupying distinct domains in the cell nucleus. Nuclear compartmentalization has recently been proposed to play an important role in genome stability but the molecular steps regulated remain to be defined. Focusing on Double strand breaks (DSBs) in response to which cells activate checkpoint and DNA repair pathways, we propose to characterize the spatial and temporal behavior of damaged chromatin and determine how this affects the maintenance of genome integrity. Currently, most studies concerning DSBs signaling and repair have been realized on asynchronous cell populations, which makes it difficult to precisely define the kinetics of events that occur at the cellular level. We thus propose to follow the nuclear localization and dynamics of an inducible DSB concomitantly with the kinetics of checkpoint activation and DNA repair at a single cell level and along the cell cycle. This will be performed using budding yeast as a model system enabling the combination of genetics, molecular biology and advanced live microscopy. We recently demonstrated that DSBs relocated to the nuclear periphery where they contact nuclear pores. This change in localization possibly regulates the choice of the repair pathway through steps that are controlled by post-translational modifications. This proposal aims at dissecting the molecular pathways defining the position of DSBs in the nucleus by performing genetic and proteomic screens, testing the functional consequence of nuclear position for checkpoint activation and DNA repair by driving the DSB to specific nuclear landmarks and, defining the dynamics of DNA damages in different repair contexts. Our project will identify new players in the DNA repair and checkpoint pathways and further our understanding of how the compartmentalization of damaged chromatin into the nucleus regulates these processes to insure the transmission of a stable genome.
Max ERC Funding
1 499 863 €
Duration
Start date: 2012-02-01, End date: 2018-01-31
Project acronym PATHOVIROME
Project Viral metagenomics of human pathologies with unknown etiology
Researcher (PI) Christelle Marie Desnues
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS7, ERC-2009-StG
Summary While viral infections create an important threat for humanity, our knowledge of the viruses that infect humans is largely incomplete. So far, discovery of new viruses has been limited by the inability to propagate them in cell culture, the lack of serological cross-reactivity, or the absence of conserved genetic element to target by PCR. Thus, numerous acute and chronic diseases with unknown etiology are caused by yet unidentified viruses. Among the highest failure rates in determining the etiological cause of disease, pneumonia, encephalitis, and pericarditis are usually cited. In these cases, the search for unknown viruses is an urgent scientific task. We propose to identify new viruses, both indigenous and pathogenic, using metagenomics (shotgun Sanger sequencing and 454 pyrosequencing) of RNA and DNA from purified viral particles found in clinical samples of individuals presenting encephalitis, pneumonia, or pericarditis diseases without known etiology. Virus-centered bioinformatics methods will be developed to detect close as well as distant relatives of known viral species. Initial viral sequence similarity analysis will be followed by full viral genome reconstruction and phylogenetic analysis. The prevalence, abundance, and geographical distribution of newly identified viruses will then be determined using quantitative real-time PCR and RT-PCR on a 10-year collection of samples from extensively characterized patients.
Summary
While viral infections create an important threat for humanity, our knowledge of the viruses that infect humans is largely incomplete. So far, discovery of new viruses has been limited by the inability to propagate them in cell culture, the lack of serological cross-reactivity, or the absence of conserved genetic element to target by PCR. Thus, numerous acute and chronic diseases with unknown etiology are caused by yet unidentified viruses. Among the highest failure rates in determining the etiological cause of disease, pneumonia, encephalitis, and pericarditis are usually cited. In these cases, the search for unknown viruses is an urgent scientific task. We propose to identify new viruses, both indigenous and pathogenic, using metagenomics (shotgun Sanger sequencing and 454 pyrosequencing) of RNA and DNA from purified viral particles found in clinical samples of individuals presenting encephalitis, pneumonia, or pericarditis diseases without known etiology. Virus-centered bioinformatics methods will be developed to detect close as well as distant relatives of known viral species. Initial viral sequence similarity analysis will be followed by full viral genome reconstruction and phylogenetic analysis. The prevalence, abundance, and geographical distribution of newly identified viruses will then be determined using quantitative real-time PCR and RT-PCR on a 10-year collection of samples from extensively characterized patients.
Max ERC Funding
831 902 €
Duration
Start date: 2010-02-01, End date: 2014-01-31
Project acronym RESPONSIVEGOV
Project Democratic Responsiveness in Comparative Perspective: How Do Democratic Governments Respond to Different Expressions of Public Opinion?
Researcher (PI) Laura Morales Diez De Ulzurrun
Host Institution (HI) FONDATION NATIONALE DES SCIENCES POLITIQUES
Call Details Starting Grant (StG), SH2, ERC-2011-StG_20101124
Summary To what extent are democratic governments responsive to citizens’ demands and preferences between elections? Are governments more likely to be responsive to the interpretation of public opinion through surveys or to collective and publicly expressed opinion –generally in the form of protests? When does one ore the other type of expression prevail as a mechanism to foster governmental responsiveness? What happens when both forms of expression of the public mood are in clear contradiction? Are certain institutional and political configurations more likely to make governments more responsive to citizens’ views between elections? Are certain political configurations more conducive to governments paying attention to opinion polls while others make them more receptive to collective action claims-making? This project will answer these questions by developing a comparative study of of governmental responsiveness in established democracies between 1980 and 2010. To this purpose, we will discuss the relevant definitions of ‘governmental responsiveness’ and ‘public opinion’, and analyse data from various sources: (i) public opinion surveys, (ii) datasets with information on protest events, (iii) news reports on public moods, collective action, and governmental activity and decision-making, and (iv) comparative indicators on institutional attributes of democratic systems. In terms of the research strategy, the project will combine the analysis of a large number of cases (20 established democracies) with a more detailed study of a set of up to 7 cases. This study will provide a highly innovative approach to the representative link between citizens and governments by comparing the dynamics of democratic representation in decision-making junctures in the periods between elections for which governments cannot invoke an electoral mandate, with the dynamics that emerge in ‘normal’ policy-making situations. The project lies at the intersection of political science and sociology.
Summary
To what extent are democratic governments responsive to citizens’ demands and preferences between elections? Are governments more likely to be responsive to the interpretation of public opinion through surveys or to collective and publicly expressed opinion –generally in the form of protests? When does one ore the other type of expression prevail as a mechanism to foster governmental responsiveness? What happens when both forms of expression of the public mood are in clear contradiction? Are certain institutional and political configurations more likely to make governments more responsive to citizens’ views between elections? Are certain political configurations more conducive to governments paying attention to opinion polls while others make them more receptive to collective action claims-making? This project will answer these questions by developing a comparative study of of governmental responsiveness in established democracies between 1980 and 2010. To this purpose, we will discuss the relevant definitions of ‘governmental responsiveness’ and ‘public opinion’, and analyse data from various sources: (i) public opinion surveys, (ii) datasets with information on protest events, (iii) news reports on public moods, collective action, and governmental activity and decision-making, and (iv) comparative indicators on institutional attributes of democratic systems. In terms of the research strategy, the project will combine the analysis of a large number of cases (20 established democracies) with a more detailed study of a set of up to 7 cases. This study will provide a highly innovative approach to the representative link between citizens and governments by comparing the dynamics of democratic representation in decision-making junctures in the periods between elections for which governments cannot invoke an electoral mandate, with the dynamics that emerge in ‘normal’ policy-making situations. The project lies at the intersection of political science and sociology.
Max ERC Funding
1 440 622 €
Duration
Start date: 2011-12-01, End date: 2018-02-28
