Project acronym AlgoFinance
Project Algorithmic Finance: Inquiring into the Reshaping of Financial Markets
Researcher (PI) Christian BORCH
Host Institution (HI) COPENHAGEN BUSINESS SCHOOL
Call Details Consolidator Grant (CoG), SH3, ERC-2016-COG
Summary Present-day financial markets are turning algorithmic, as market orders are increasingly being executed by fully automated computer algorithms, without any direct human intervention. Although algorithmic finance seems to fundamentally reshape the central dynamics in financial markets, and even though it prompts core sociological questions, it has not yet received any systematic attention. In a pioneering contribution to economic sociology and social studies of finance, ALGOFINANCE aims to understand how and with what consequences the turn to algorithms is changing financial markets. The overall concept and central contributions of ALGOFINANCE are the following: (1) on an intra-firm level, the project examines how the shift to algorithmic finance reshapes the ways in which trading firms operate, and does so by systematically and empirically investigating the reconfiguration of organizational structures and employee subjectivity; (2) on an inter-algorithmic level, it offers a ground-breaking methodology (agent-based modelling informed by qualitative data) to grasp how trading algorithms interact with one another in a fully digital space; and (3) on the level of market sociality, it proposes a novel theorization of how intra-firm and inter-algorithmic dynamics can be conceived of as introducing a particular form of sociality that is characteristic to algorithmic finance: a form of sociality-as-association heuristically analyzed as imitation. None of these three levels have received systematic attention in the state-of-the-art literature. Addressing them will significantly advance the understanding of present-day algorithmic finance in economic sociology. By contributing novel empirical, methodological, and theoretical understandings of the functioning and consequences of algorithms, ALGOFINANCE will pave the way for other research into digital sociology and the broader algorithmization of society.
Summary
Present-day financial markets are turning algorithmic, as market orders are increasingly being executed by fully automated computer algorithms, without any direct human intervention. Although algorithmic finance seems to fundamentally reshape the central dynamics in financial markets, and even though it prompts core sociological questions, it has not yet received any systematic attention. In a pioneering contribution to economic sociology and social studies of finance, ALGOFINANCE aims to understand how and with what consequences the turn to algorithms is changing financial markets. The overall concept and central contributions of ALGOFINANCE are the following: (1) on an intra-firm level, the project examines how the shift to algorithmic finance reshapes the ways in which trading firms operate, and does so by systematically and empirically investigating the reconfiguration of organizational structures and employee subjectivity; (2) on an inter-algorithmic level, it offers a ground-breaking methodology (agent-based modelling informed by qualitative data) to grasp how trading algorithms interact with one another in a fully digital space; and (3) on the level of market sociality, it proposes a novel theorization of how intra-firm and inter-algorithmic dynamics can be conceived of as introducing a particular form of sociality that is characteristic to algorithmic finance: a form of sociality-as-association heuristically analyzed as imitation. None of these three levels have received systematic attention in the state-of-the-art literature. Addressing them will significantly advance the understanding of present-day algorithmic finance in economic sociology. By contributing novel empirical, methodological, and theoretical understandings of the functioning and consequences of algorithms, ALGOFINANCE will pave the way for other research into digital sociology and the broader algorithmization of society.
Max ERC Funding
1 590 036 €
Duration
Start date: 2017-05-01, End date: 2021-04-30
Project acronym Amitochondriates
Project Life without mitochondrion
Researcher (PI) Vladimir HAMPL
Host Institution (HI) UNIVERZITA KARLOVA
Call Details Consolidator Grant (CoG), LS8, ERC-2017-COG
Summary Mitochondria are often referred to as the “power houses” of eukaryotic cells. All eukaryotes were thought to have mitochondria of some form until 2016, when the first eukaryote thriving without mitochondria was discovered by our laboratory – a flagellate Monocercomonoides. Understanding cellular functions of these cells, which represent a new functional type of eukaryotes, and understanding the circumstances of the unique event of mitochondrial loss are motivations for this proposal. The first objective focuses on the cell physiology. We will perform a metabolomic study revealing major metabolic pathways and concentrate further on elucidating its unique system of iron-sulphur cluster assembly. In the second objective, we will investigate in details the unique case of mitochondrial loss. We will examine two additional potentially amitochondriate lineages by means of genomics and transcriptomics, conduct experiments simulating the moments of mitochondrial loss and try to induce the mitochondrial loss in vitro by knocking out or down genes for mitochondrial biogenesis. We have chosen Giardia intestinalis and Entamoeba histolytica as models for the latter experiments, because their mitochondria are already reduced to minimalistic “mitosomes” and because some genetic tools are already available for them. Successful mitochondrial knock-outs would enable us to study mitochondrial loss in ‘real time’ and in vivo. In the third objective, we will focus on transforming Monocercomonoides into a tractable laboratory model by developing methods of axenic cultivation and genetic manipulation. This will open new possibilities in the studies of this organism and create a cell culture representing an amitochondriate model for cell biological studies enabling the dissection of mitochondrial effects from those of other compartments. The team is composed of the laboratory of PI and eight invited experts and we hope it has the ability to address these challenging questions.
Summary
Mitochondria are often referred to as the “power houses” of eukaryotic cells. All eukaryotes were thought to have mitochondria of some form until 2016, when the first eukaryote thriving without mitochondria was discovered by our laboratory – a flagellate Monocercomonoides. Understanding cellular functions of these cells, which represent a new functional type of eukaryotes, and understanding the circumstances of the unique event of mitochondrial loss are motivations for this proposal. The first objective focuses on the cell physiology. We will perform a metabolomic study revealing major metabolic pathways and concentrate further on elucidating its unique system of iron-sulphur cluster assembly. In the second objective, we will investigate in details the unique case of mitochondrial loss. We will examine two additional potentially amitochondriate lineages by means of genomics and transcriptomics, conduct experiments simulating the moments of mitochondrial loss and try to induce the mitochondrial loss in vitro by knocking out or down genes for mitochondrial biogenesis. We have chosen Giardia intestinalis and Entamoeba histolytica as models for the latter experiments, because their mitochondria are already reduced to minimalistic “mitosomes” and because some genetic tools are already available for them. Successful mitochondrial knock-outs would enable us to study mitochondrial loss in ‘real time’ and in vivo. In the third objective, we will focus on transforming Monocercomonoides into a tractable laboratory model by developing methods of axenic cultivation and genetic manipulation. This will open new possibilities in the studies of this organism and create a cell culture representing an amitochondriate model for cell biological studies enabling the dissection of mitochondrial effects from those of other compartments. The team is composed of the laboratory of PI and eight invited experts and we hope it has the ability to address these challenging questions.
Max ERC Funding
1 935 500 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym ArtHep
Project Hepatocytes-Like Microreactors for Liver Tissue Engineering
Researcher (PI) Brigitte STADLER
Host Institution (HI) AARHUS UNIVERSITET
Call Details Consolidator Grant (CoG), LS9, ERC-2018-COG
Summary The global epidemics of obesity and diabetes type 2 lead to higher abundancy of medical conditions like non-alcoholic fatty liver disease causing an increase in liver failure and demand for liver transplants. The shortage of donor organs and the insufficient success in tissue engineering to ex vivo grow complex organs like the liver is a global medical challenge.
ArtHep targets the assembly of hepatic-like tissue, consisting of biological and synthetic entities, mimicking the core structure elements and key functions of the liver. ArtHep comprises an entirely new concept in liver regeneration with multi-angled core impact: i) cell mimics are expected to reduce the pressure to obtain donor cells, ii) the integrated biocatalytic subunits are destined to take over tasks of the damaged liver slowing down the progress of liver damage, and iii) the matching micro-environment in the bioprinted tissue is anticipated to facilitate the connection between the transplant and the liver.
Success criteria of ArtHep include engineering enzyme-mimics, which can perform core biocatalytic conversions similar to the liver, the assembly of biocatalytic active subunits and their encapsulation in cell-like carriers (microreactors), which have mechanical properties that match the liver tissue and that have a camouflaging coating to mimic the surface cues of liver tissue-relevant cells. Finally, matured bioprinted liver-lobules consisting of microreactors and live cells need to connect to liver tissue when transplanted into rats.
I am convinced that the ground-breaking research in ArtHep will contribute to the excellence of science in Europe while providing the game-changing foundation to counteract the ever increasing donor liver shortage. Further, consolidating my scientific efforts and moving them forward into unexplored dimensions in biomimicry for medical purposes, is a unique opportunity to advance my career.
Summary
The global epidemics of obesity and diabetes type 2 lead to higher abundancy of medical conditions like non-alcoholic fatty liver disease causing an increase in liver failure and demand for liver transplants. The shortage of donor organs and the insufficient success in tissue engineering to ex vivo grow complex organs like the liver is a global medical challenge.
ArtHep targets the assembly of hepatic-like tissue, consisting of biological and synthetic entities, mimicking the core structure elements and key functions of the liver. ArtHep comprises an entirely new concept in liver regeneration with multi-angled core impact: i) cell mimics are expected to reduce the pressure to obtain donor cells, ii) the integrated biocatalytic subunits are destined to take over tasks of the damaged liver slowing down the progress of liver damage, and iii) the matching micro-environment in the bioprinted tissue is anticipated to facilitate the connection between the transplant and the liver.
Success criteria of ArtHep include engineering enzyme-mimics, which can perform core biocatalytic conversions similar to the liver, the assembly of biocatalytic active subunits and their encapsulation in cell-like carriers (microreactors), which have mechanical properties that match the liver tissue and that have a camouflaging coating to mimic the surface cues of liver tissue-relevant cells. Finally, matured bioprinted liver-lobules consisting of microreactors and live cells need to connect to liver tissue when transplanted into rats.
I am convinced that the ground-breaking research in ArtHep will contribute to the excellence of science in Europe while providing the game-changing foundation to counteract the ever increasing donor liver shortage. Further, consolidating my scientific efforts and moving them forward into unexplored dimensions in biomimicry for medical purposes, is a unique opportunity to advance my career.
Max ERC Funding
1 992 289 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym BEHAVFRICTIONS
Project Behavioral Implications of Information-Processing Frictions
Researcher (PI) Jakub STEINER
Host Institution (HI) NARODOHOSPODARSKY USTAV AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE
Call Details Consolidator Grant (CoG), SH1, ERC-2017-COG
Summary BEHAVFRICTIONS will use novel models focussing on information-processing frictions to explain choice patterns described in behavioral economics and psychology. The proposed research will provide microfoundations that are essential for (i) identification of stable preferences, (ii) counterfactual predictions, and (iii) normative conclusions.
(i) Agents who face information-processing costs must trade the precision of choice against information costs. Their behavior thus reflects both their stable preferences and the context-dependent procedures that manage their errors stemming from imperfect information processing. In the absence of micro-founded models, the two drivers of the behavior are difficult to disentangle for outside observers. In some pillars of the proposal, the agents follow choice rules that closely resemble logit rules used in structural estimation. This will allow me to reinterpret the structural estimation fits to choice data and to make a distinction between the stable preferences and frictions.
(ii) Such a distinction is important in counterfactual policy analysis because the second-best decision procedures that manage the errors in choice are affected by the analysed policy. Incorporation of the information-processing frictions into existing empirical methods will improve our ability to predict effects of the policies.
(iii) My preliminary results suggest that when an agent is prone to committing errors, biases--such as overconfidence, confirmatory bias, or perception biases known from prospect theory--arise under second-best strategies. By providing the link between the agent's environment and the second-best distribution of the perception errors, my models will delineate environments in which these biases shield the agents from the most costly mistakes from environments in which the biases turn into maladaptations. The distinction will inform the normative debate on debiasing.
Summary
BEHAVFRICTIONS will use novel models focussing on information-processing frictions to explain choice patterns described in behavioral economics and psychology. The proposed research will provide microfoundations that are essential for (i) identification of stable preferences, (ii) counterfactual predictions, and (iii) normative conclusions.
(i) Agents who face information-processing costs must trade the precision of choice against information costs. Their behavior thus reflects both their stable preferences and the context-dependent procedures that manage their errors stemming from imperfect information processing. In the absence of micro-founded models, the two drivers of the behavior are difficult to disentangle for outside observers. In some pillars of the proposal, the agents follow choice rules that closely resemble logit rules used in structural estimation. This will allow me to reinterpret the structural estimation fits to choice data and to make a distinction between the stable preferences and frictions.
(ii) Such a distinction is important in counterfactual policy analysis because the second-best decision procedures that manage the errors in choice are affected by the analysed policy. Incorporation of the information-processing frictions into existing empirical methods will improve our ability to predict effects of the policies.
(iii) My preliminary results suggest that when an agent is prone to committing errors, biases--such as overconfidence, confirmatory bias, or perception biases known from prospect theory--arise under second-best strategies. By providing the link between the agent's environment and the second-best distribution of the perception errors, my models will delineate environments in which these biases shield the agents from the most costly mistakes from environments in which the biases turn into maladaptations. The distinction will inform the normative debate on debiasing.
Max ERC Funding
1 321 488 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym CLIC
Project Classical Influences and Irish Culture
Researcher (PI) Isabelle Torrance
Host Institution (HI) AARHUS UNIVERSITET
Call Details Consolidator Grant (CoG), SH5, ERC-2018-COG
Summary The hypothesis of this project is that Ireland has a unique and hitherto underexplored history of cultural engagement with models from ancient Greece and Rome. Unlike Britain and mainland Europe, Ireland was never part of the Roman Empire. Yet the island has an extraordinarily vibrant tradition of classical learning that dates back to its earliest recorded literature, and is unparalleled in other northern European countries. Research for this project will address why this is the case, by examining sources through nine significant diachronic themes identified by the PI: language; land; travel and exile; Troy; satire; Neoplatonism; female voices; material culture; and global influence. This multi-thematic approach will enable analysis of what is remarkable about classical reception in Ireland. It will also provide a heuristic framework that generates dialogue between normally disparate fields, such as classical reception studies, Irish and British history, English-language literature, Irish-language literature, medieval studies, postcolonial studies, philosophy, material culture, women's studies, and global studies. The project will engage with contemporary preoccupations surrounding the politics and history of the divided island of Ireland, such as the current decade of centenary commemorations for the foundation of an independent Irish state (1912-1922, 2012-2022), and the on-going violence and political divisions in Northern Ireland. These issues will serve as a springboard for opening new avenues of investigation that look far beyond the past 100 years, but are linked to them. The project will thus shed new light on the role of classical culture in shaping literary, social, and political discourse across the island of Ireland, and throughout its history.
Summary
The hypothesis of this project is that Ireland has a unique and hitherto underexplored history of cultural engagement with models from ancient Greece and Rome. Unlike Britain and mainland Europe, Ireland was never part of the Roman Empire. Yet the island has an extraordinarily vibrant tradition of classical learning that dates back to its earliest recorded literature, and is unparalleled in other northern European countries. Research for this project will address why this is the case, by examining sources through nine significant diachronic themes identified by the PI: language; land; travel and exile; Troy; satire; Neoplatonism; female voices; material culture; and global influence. This multi-thematic approach will enable analysis of what is remarkable about classical reception in Ireland. It will also provide a heuristic framework that generates dialogue between normally disparate fields, such as classical reception studies, Irish and British history, English-language literature, Irish-language literature, medieval studies, postcolonial studies, philosophy, material culture, women's studies, and global studies. The project will engage with contemporary preoccupations surrounding the politics and history of the divided island of Ireland, such as the current decade of centenary commemorations for the foundation of an independent Irish state (1912-1922, 2012-2022), and the on-going violence and political divisions in Northern Ireland. These issues will serve as a springboard for opening new avenues of investigation that look far beyond the past 100 years, but are linked to them. The project will thus shed new light on the role of classical culture in shaping literary, social, and political discourse across the island of Ireland, and throughout its history.
Max ERC Funding
1 888 592 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym CLIOARCH
Project Cliodynamic archaeology: Computational approaches to Final Palaeolithic/earliest Mesolithic archaeology and climate change
Researcher (PI) Felix RIEDE
Host Institution (HI) AARHUS UNIVERSITET
Call Details Consolidator Grant (CoG), SH6, ERC-2018-COG
Summary Late Pleistocene/early Holocene Europe is said to be the ideal laboratory for the investigation of human responses to rapidly changing climates and environments, migration and adaptation. Yet, pinpointing precisely how and why contemporaneous Final Palaeolithic/earliest Mesolithic (15,000-11,000 years BP) foragers migrated, and which environmental or other factors they adapted to – or failed to – has remained remarkably elusive. At the core of ClioArch is the radical but, in light of research-historical insights, necessary hypothesis that the current archaeological cultural taxonomy for this iconic period of European prehistory is epistemologically flawed and that operationalisations and interpretations based on this traditional taxonomy – especially those that seek to relate observed changes in material culture and land-use to contemporaneous climatic and environmental changes – are therefore problematic. Hence, novel approaches to crafting the taxonomic building blocks are required, as are novel analyses of human|environment relations in this period. ClioArch’s premier ambition is to provide operational cultural taxonomies for the Final Palaeolithic/earliest Mesolithic of Europe and to couple these with interdisciplinary cultural evolutionary, quantitative ecological methods and field archaeological investigations beyond the state-of-the-art, so as to better capture such adaptations – almost certainly with major implications for the standard culture-historical narrative relating to this period. In so doing, the project will pioneer a fully transparent and replicable – and eminently transferable – methodology for the study of the impacts of climate change and extreme environmental events in deep history. In turn, such a quantitative understanding of past adaptive dynamics will position archaeology more centrally in contemporary debates about climate change, environmental catastrophe and their cultural dimensions.
Summary
Late Pleistocene/early Holocene Europe is said to be the ideal laboratory for the investigation of human responses to rapidly changing climates and environments, migration and adaptation. Yet, pinpointing precisely how and why contemporaneous Final Palaeolithic/earliest Mesolithic (15,000-11,000 years BP) foragers migrated, and which environmental or other factors they adapted to – or failed to – has remained remarkably elusive. At the core of ClioArch is the radical but, in light of research-historical insights, necessary hypothesis that the current archaeological cultural taxonomy for this iconic period of European prehistory is epistemologically flawed and that operationalisations and interpretations based on this traditional taxonomy – especially those that seek to relate observed changes in material culture and land-use to contemporaneous climatic and environmental changes – are therefore problematic. Hence, novel approaches to crafting the taxonomic building blocks are required, as are novel analyses of human|environment relations in this period. ClioArch’s premier ambition is to provide operational cultural taxonomies for the Final Palaeolithic/earliest Mesolithic of Europe and to couple these with interdisciplinary cultural evolutionary, quantitative ecological methods and field archaeological investigations beyond the state-of-the-art, so as to better capture such adaptations – almost certainly with major implications for the standard culture-historical narrative relating to this period. In so doing, the project will pioneer a fully transparent and replicable – and eminently transferable – methodology for the study of the impacts of climate change and extreme environmental events in deep history. In turn, such a quantitative understanding of past adaptive dynamics will position archaeology more centrally in contemporary debates about climate change, environmental catastrophe and their cultural dimensions.
Max ERC Funding
1 907 638 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym ConTExt
Project Connecting the Extreme
Researcher (PI) Sune Toft
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Consolidator Grant (CoG), PE9, ERC-2014-CoG
Summary Advances in technology and methodology over the last decade, have enabled the study of galaxies to the highest redshifts. This has revolutionized our understanding of the origin and evolution of galaxies. I have played a central role in this revolution, by discovering that at z=2, when the universe was only 3 Gyr old, half of the most massive galaxies were extremely compact and had already completed their star formation. During the last five years I have led a successful group of postdocs and students dedicated to investigating the extreme properties of these galaxies and place them into cosmological context. Combining a series of high profile observational studies published by my group and others, I recently proposed an evolutionary sequence that ties together the most extreme galaxies in the universe, from the most intense dusty starburst at cosmic dawn, through quasars: the brightest sources in the universe, driven by feedback from supermassive black holes, and galaxy cores hosting the densest conglomerations of stellar mass known, to the sleeping giants of the local universe, the giant ellipticals. The proposed research program will explore if such an evolutionary sequence exists, with the ultimate goal of reaching, for the first time, a coherent physical understanding of how the most massive galaxies in the universe formed. While there is a chance the rigorous tests may ultimately reveal the proposed sequence to be too simplistic, a guarantied outcome of the program is a significantly improved understanding of the physical mechanisms that shape galaxies and drive their star formation and quenching
Summary
Advances in technology and methodology over the last decade, have enabled the study of galaxies to the highest redshifts. This has revolutionized our understanding of the origin and evolution of galaxies. I have played a central role in this revolution, by discovering that at z=2, when the universe was only 3 Gyr old, half of the most massive galaxies were extremely compact and had already completed their star formation. During the last five years I have led a successful group of postdocs and students dedicated to investigating the extreme properties of these galaxies and place them into cosmological context. Combining a series of high profile observational studies published by my group and others, I recently proposed an evolutionary sequence that ties together the most extreme galaxies in the universe, from the most intense dusty starburst at cosmic dawn, through quasars: the brightest sources in the universe, driven by feedback from supermassive black holes, and galaxy cores hosting the densest conglomerations of stellar mass known, to the sleeping giants of the local universe, the giant ellipticals. The proposed research program will explore if such an evolutionary sequence exists, with the ultimate goal of reaching, for the first time, a coherent physical understanding of how the most massive galaxies in the universe formed. While there is a chance the rigorous tests may ultimately reveal the proposed sequence to be too simplistic, a guarantied outcome of the program is a significantly improved understanding of the physical mechanisms that shape galaxies and drive their star formation and quenching
Max ERC Funding
1 999 526 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym CRIMTANG
Project Criminal Entanglements.A new ethnographic approach to transnational organised crime.
Researcher (PI) Henrik VIGH
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Consolidator Grant (CoG), SH3, ERC-2016-COG
Summary Linked to terrorism, moral breakdown, and societal decay, Transnational Organised Crime (TOC) has come to embody current global anxieties as a figure of fear and cause of disquiet. Yet despite its central position on the social and political radar, our knowledge of it remains limited and fragmentary. Quantitative analyses may have identified the scale of the problem, but its underlying socio-cultural logic and practices remain under-researched and largely obscure. TOC is on the rise, and we need better insights into how it develops and expands, who engages in it and why, and how it is linked to and embedded in social networks that straddle countries and contexts.
CRIMTANG proposes a unique approach to the study of the social infrastructure of contemporary TOC. It develops a research strategy that is ethnographic and transnational in design and so attuned to the human flows and formations of TOC. The project comprises a trans-disciplinary research team of anthropologists, criminologists and political scientists, and builds on their prior experience of the people, regions and languages under study. It explores the illegal and overlapping flows of migrants and drugs from North-West Africa into Europe, following a key trafficking trajectory stretching from Tangiers to Barcelona, Paris and beyond.
In so doing, CRIMTANG sheds new light on the actual empirical processes in operation at different points along this trafficking route, whilst simultaneously developing new theoretical and methodological apparatuses for apprehending TOC that can be exported and applied in other regions and contexts. It reimagines the idea of social entanglement and proposes new transnational and collective fieldwork strategies. Finally, it will advance and consolidate the European research environment on TOC by creating a research hub for transnational ethnographic criminology at the University of Copenhagen.
Summary
Linked to terrorism, moral breakdown, and societal decay, Transnational Organised Crime (TOC) has come to embody current global anxieties as a figure of fear and cause of disquiet. Yet despite its central position on the social and political radar, our knowledge of it remains limited and fragmentary. Quantitative analyses may have identified the scale of the problem, but its underlying socio-cultural logic and practices remain under-researched and largely obscure. TOC is on the rise, and we need better insights into how it develops and expands, who engages in it and why, and how it is linked to and embedded in social networks that straddle countries and contexts.
CRIMTANG proposes a unique approach to the study of the social infrastructure of contemporary TOC. It develops a research strategy that is ethnographic and transnational in design and so attuned to the human flows and formations of TOC. The project comprises a trans-disciplinary research team of anthropologists, criminologists and political scientists, and builds on their prior experience of the people, regions and languages under study. It explores the illegal and overlapping flows of migrants and drugs from North-West Africa into Europe, following a key trafficking trajectory stretching from Tangiers to Barcelona, Paris and beyond.
In so doing, CRIMTANG sheds new light on the actual empirical processes in operation at different points along this trafficking route, whilst simultaneously developing new theoretical and methodological apparatuses for apprehending TOC that can be exported and applied in other regions and contexts. It reimagines the idea of social entanglement and proposes new transnational and collective fieldwork strategies. Finally, it will advance and consolidate the European research environment on TOC by creating a research hub for transnational ethnographic criminology at the University of Copenhagen.
Max ERC Funding
1 999 909 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym D-FENS
Project Dicer-Dependent Defense in Mammals
Researcher (PI) Petr Svoboda
Host Institution (HI) USTAV MOLEKULARNI GENETIKY AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE
Call Details Consolidator Grant (CoG), LS2, ERC-2014-CoG
Summary Viral infection or retrotransposon expansion in the genome often result in production of double-stranded RNA (dsRNA). dsRNA can be intercepted by RNase III Dicer acting in the RNA interference (RNAi) pathway, an ancient eukaryotic defense mechanism. Notably, endogenous mammalian RNAi appears dormant while its common and unique physiological roles remain poorly understood. A factor underlying mammalian RNAi dormancy is inefficient processing of dsRNA by the full-length Dicer. Yet, a simple truncation of Dicer leads to hyperactive RNAi, which is naturally present in mouse oocytes.
The D-FENS project will use genetic animal models to define common, cell-specific and species-specific roles of mammalian RNAi. D-FENS has three complementary and synergizing objectives:
(1) Explore consequences of hyperactive RNAi in vivo. A mouse expressing a truncated Dicer will reveal at the organismal level any negative effect of hyperactive RNAi, the relationship between RNAi and mammalian immune system, and potential of RNAi to suppress viral infections in mammals.
(2) Define common and species-specific features of RNAi in the oocyte. Functional and bioinformatics analyses in mouse, bovine, and hamster oocytes will define rules and exceptions concerning endogenous RNAi roles, including RNAi contribution to maternal mRNA degradation and co-existence with the miRNA pathway.
(3) Uncover relationship between RNAi and piRNA pathways in suppression of retrotransposons. We hypothesize that hyperactive RNAi in mouse oocytes functionally complements the piRNA pathway, a Dicer-independent pathway suppressing retrotransposons in the germline. Using genetic models, we will explore unique and redundant roles of both pathways in the germline.
D-FENS will uncover physiological significance of the N-terminal part of Dicer, fundamentally improve understanding RNAi function in the germline, and provide a critical in vivo assessment of antiviral activity of RNAi with implications for human therapy.
Summary
Viral infection or retrotransposon expansion in the genome often result in production of double-stranded RNA (dsRNA). dsRNA can be intercepted by RNase III Dicer acting in the RNA interference (RNAi) pathway, an ancient eukaryotic defense mechanism. Notably, endogenous mammalian RNAi appears dormant while its common and unique physiological roles remain poorly understood. A factor underlying mammalian RNAi dormancy is inefficient processing of dsRNA by the full-length Dicer. Yet, a simple truncation of Dicer leads to hyperactive RNAi, which is naturally present in mouse oocytes.
The D-FENS project will use genetic animal models to define common, cell-specific and species-specific roles of mammalian RNAi. D-FENS has three complementary and synergizing objectives:
(1) Explore consequences of hyperactive RNAi in vivo. A mouse expressing a truncated Dicer will reveal at the organismal level any negative effect of hyperactive RNAi, the relationship between RNAi and mammalian immune system, and potential of RNAi to suppress viral infections in mammals.
(2) Define common and species-specific features of RNAi in the oocyte. Functional and bioinformatics analyses in mouse, bovine, and hamster oocytes will define rules and exceptions concerning endogenous RNAi roles, including RNAi contribution to maternal mRNA degradation and co-existence with the miRNA pathway.
(3) Uncover relationship between RNAi and piRNA pathways in suppression of retrotransposons. We hypothesize that hyperactive RNAi in mouse oocytes functionally complements the piRNA pathway, a Dicer-independent pathway suppressing retrotransposons in the germline. Using genetic models, we will explore unique and redundant roles of both pathways in the germline.
D-FENS will uncover physiological significance of the N-terminal part of Dicer, fundamentally improve understanding RNAi function in the germline, and provide a critical in vivo assessment of antiviral activity of RNAi with implications for human therapy.
Max ERC Funding
1 950 000 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym DDRegulation
Project Regulation of DNA damage responses at the replication fork
Researcher (PI) Niels Mailand
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Consolidator Grant (CoG), LS1, ERC-2013-CoG
Summary This project aims at delineating the regulatory signaling processes that enable cells to overcome DNA damage during DNA replication, a major challenge to the integrity of the genome as the normal replication machinery is unable to replicate past DNA lesions. This may result in collapse of the replication fork, potentially giving rise to gross genomic alterations. To mitigate this threat, all cells have evolved DNA damage bypass strategies such as translesion DNA synthesis (TLS), involving low fidelity DNA polymerases that can replicate damaged DNA, albeit in an error-prone manner, offering a trade-off between limited mutagenesis and gross chromosomal instability. How DNA damage bypass pathways are regulated and integrated with DNA replication and repair remain poorly resolved questions fundamental to understanding genome stability maintenance and disease onset. Regulatory signaling mediated by the small modifier protein ubiquitin has a prominent role in orchestrating the reorganization of the replication fork necessary for overcoming DNA lesions, but this involvement has not been systematically explored. To remedy these gaps in our knowledge, I propose to implement a series of innovative complementary strategies to isolate and identify the regulatory factors and ubiquitin-dependent processes that promote DNA damage responses at the replication fork, allowing for subsequent in-depth characterization of their roles in protecting genome integrity by targeted functional studies. This project will enable an advanced level of mechanistic insight into key regulatory processes underlying replication-associated DNA damage responses that has not been feasible to achieve with exisiting methodologies, providing a realistic outlook for groundbreaking discoveries that will open up many new avenues for further research into mechanisms and biological functions of regulatory signaling processes in the DNA damage response and beyond.
Summary
This project aims at delineating the regulatory signaling processes that enable cells to overcome DNA damage during DNA replication, a major challenge to the integrity of the genome as the normal replication machinery is unable to replicate past DNA lesions. This may result in collapse of the replication fork, potentially giving rise to gross genomic alterations. To mitigate this threat, all cells have evolved DNA damage bypass strategies such as translesion DNA synthesis (TLS), involving low fidelity DNA polymerases that can replicate damaged DNA, albeit in an error-prone manner, offering a trade-off between limited mutagenesis and gross chromosomal instability. How DNA damage bypass pathways are regulated and integrated with DNA replication and repair remain poorly resolved questions fundamental to understanding genome stability maintenance and disease onset. Regulatory signaling mediated by the small modifier protein ubiquitin has a prominent role in orchestrating the reorganization of the replication fork necessary for overcoming DNA lesions, but this involvement has not been systematically explored. To remedy these gaps in our knowledge, I propose to implement a series of innovative complementary strategies to isolate and identify the regulatory factors and ubiquitin-dependent processes that promote DNA damage responses at the replication fork, allowing for subsequent in-depth characterization of their roles in protecting genome integrity by targeted functional studies. This project will enable an advanced level of mechanistic insight into key regulatory processes underlying replication-associated DNA damage responses that has not been feasible to achieve with exisiting methodologies, providing a realistic outlook for groundbreaking discoveries that will open up many new avenues for further research into mechanisms and biological functions of regulatory signaling processes in the DNA damage response and beyond.
Max ERC Funding
1 996 356 €
Duration
Start date: 2014-07-01, End date: 2019-06-30
