Project acronym CAPTURE
Project CApturing Paradata for documenTing data creation and Use for the REsearch of the future
Researcher (PI) Isto HUVILA
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), SH3, ERC-2018-COG
Summary "Considerable investments have been made in Europe and worldwide in research data infrastructures. Instead of a general lack of data about data, it has become apparent that the pivotal factor that drastically constrains the use of data is the absence of contextual knowledge about how data was created and how it has been used. This applies especially to many branches of SSH research where data is highly heterogeneous, both by its kind (e.g. being qualitative, quantitative, naturalistic, purposefully created) and origins (e.g. being historical/contemporary, from different contexts and geographical places). The problem is that there may be enough metadata (data about data) but there is too little paradata (data on the processes of its creation and use).
In contrast to the rather straightforward problem of describing the data, the high-risk/high-gain problem no-one has managed to solve, is the lack of comprehensive understanding of what information about the creation and use of research data is needed and how to capture enough of that information to make the data reusable and to avoid the risk that currently collected vast amounts of research data become useless in the future. The wickedness of the problem lies in the practical impossibility to document and keep everything and the difficulty to determine optimal procedures for capturing just enough.
With an empirical focus on archaeological and cultural heritage data, which stands out by its extreme heterogeneity and rapid accumulation due to the scale of ongoing development-led archaeological fieldwork, CAPTURE develops an in-depth understanding of how paradata is #1 created and #2 used at the moment, #3 elicits methods for capturing paradata on the basis of the findings of #1-2, #4 tests the new methods in field trials, and #5 synthesises the findings in a reference model to inform the capturing of paradata and enabling data-intensive research using heterogeneous research data stemming from diverse origins.
"
Summary
"Considerable investments have been made in Europe and worldwide in research data infrastructures. Instead of a general lack of data about data, it has become apparent that the pivotal factor that drastically constrains the use of data is the absence of contextual knowledge about how data was created and how it has been used. This applies especially to many branches of SSH research where data is highly heterogeneous, both by its kind (e.g. being qualitative, quantitative, naturalistic, purposefully created) and origins (e.g. being historical/contemporary, from different contexts and geographical places). The problem is that there may be enough metadata (data about data) but there is too little paradata (data on the processes of its creation and use).
In contrast to the rather straightforward problem of describing the data, the high-risk/high-gain problem no-one has managed to solve, is the lack of comprehensive understanding of what information about the creation and use of research data is needed and how to capture enough of that information to make the data reusable and to avoid the risk that currently collected vast amounts of research data become useless in the future. The wickedness of the problem lies in the practical impossibility to document and keep everything and the difficulty to determine optimal procedures for capturing just enough.
With an empirical focus on archaeological and cultural heritage data, which stands out by its extreme heterogeneity and rapid accumulation due to the scale of ongoing development-led archaeological fieldwork, CAPTURE develops an in-depth understanding of how paradata is #1 created and #2 used at the moment, #3 elicits methods for capturing paradata on the basis of the findings of #1-2, #4 tests the new methods in field trials, and #5 synthesises the findings in a reference model to inform the capturing of paradata and enabling data-intensive research using heterogeneous research data stemming from diverse origins.
"
Max ERC Funding
1 944 162 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym CONPOL
Project Contexts, networks and participation: The social logic of political engagement
Researcher (PI) Sven Aron Oskarsson
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), SH2, ERC-2015-CoG
Summary The statement that individuals’ immediate social circumstances influence how they think and act in the political sphere is a truism. However, both theoretical and empirical considerations have often prevented political scientists from incorporating this logic into analyses of political behavior. In the CONPOL project we argue that it is necessary to return to the idea that politics follows a social logic in order to push the theoretical and empirical boundaries in explaining political behavior. That is, people do not act as isolated individuals when confronting complex political tasks such as deciding whether to vote and which party or candidate to vote for. Instead politics should be seen as a social experience in which individuals arrive at their decisions within particular social settings: the family, the peer group, the workplace, the neighborhood. In what way do parents and other family members influence an individual’s political choices? What is the role of workmates and neighbors when individuals arrive at political decisions? Do friends and friends’ friends affect how you think and act in the political sphere? To answer such questions the standard approach to gather empirical evidence on political behavior based on national sample surveys needs to be complemented by the use of population wide register data. The empirical core of the CONPOL project is unique Swedish register data. Via the population registers provided by Statistics Sweden it is possible to identify several relevant social settings such as parent-child relations and the location of individuals within workplaces and neighborhoods. The registers also allow us to identify certain network links between individuals. Furthermore, Statistics Sweden holds information on several variables measuring important political traits. A major aim for CONPOL is to complement this information by scanning in and digitalizing election rolls with individual-level information on turnout across several elections.
Summary
The statement that individuals’ immediate social circumstances influence how they think and act in the political sphere is a truism. However, both theoretical and empirical considerations have often prevented political scientists from incorporating this logic into analyses of political behavior. In the CONPOL project we argue that it is necessary to return to the idea that politics follows a social logic in order to push the theoretical and empirical boundaries in explaining political behavior. That is, people do not act as isolated individuals when confronting complex political tasks such as deciding whether to vote and which party or candidate to vote for. Instead politics should be seen as a social experience in which individuals arrive at their decisions within particular social settings: the family, the peer group, the workplace, the neighborhood. In what way do parents and other family members influence an individual’s political choices? What is the role of workmates and neighbors when individuals arrive at political decisions? Do friends and friends’ friends affect how you think and act in the political sphere? To answer such questions the standard approach to gather empirical evidence on political behavior based on national sample surveys needs to be complemented by the use of population wide register data. The empirical core of the CONPOL project is unique Swedish register data. Via the population registers provided by Statistics Sweden it is possible to identify several relevant social settings such as parent-child relations and the location of individuals within workplaces and neighborhoods. The registers also allow us to identify certain network links between individuals. Furthermore, Statistics Sweden holds information on several variables measuring important political traits. A major aim for CONPOL is to complement this information by scanning in and digitalizing election rolls with individual-level information on turnout across several elections.
Max ERC Funding
1 621 940 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym DELMIT
Project Maintaining the Human Mitochondrial Genome
Researcher (PI) Maria Falkenberg Gustafsson
Host Institution (HI) GOETEBORGS UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), LS1, ERC-2015-CoG
Summary Mitochondria are required to convert food into usable energy forms and every cell contains thousands of them. Unlike most other cellular compartments, mitochondria have their own genomes (mtDNA) that encode for 13 of the about 90 proteins present in the respiratory chain. All proteins necessary for mtDNA replication, as well as transcription and translation of mtDNA-encoded genes, are encoded in the nucleus. Mutations in nuclear-encoded proteins required for mtDNA maintenance is an important cause of neurodegeneration and muscle diseases. The common result of these defects is either mtDNA depletion or accumulation of multiple deletions of mtDNA in postmitotic tissues.
The long-term goal (or vision) of research in my laboratory is to understand in molecular detail how mtDNA is replicated and how this process is regulated in mammalian cells. To this end we use a protein biochemistry approach, which we combine with in vivo verification in cell lines. My group was in 2004 the first to reconstitute mtDNA replication in vitro and we have continued to develop even more elaborate system ever since. In the current application, the major focus is studies of the mitochondrial D-loop region, a triple-stranded structure in the mitochondrial genome. The D-loop functions as a regulatory hub and we will determine how initiation and termination of mtDNA replication is controlled from this region. We will also determine the physical organization of the mtDNA replication machinery at the replication fork and establish how mtDNA deletions, a classical hallmark of human ageing, are formed.
Summary
Mitochondria are required to convert food into usable energy forms and every cell contains thousands of them. Unlike most other cellular compartments, mitochondria have their own genomes (mtDNA) that encode for 13 of the about 90 proteins present in the respiratory chain. All proteins necessary for mtDNA replication, as well as transcription and translation of mtDNA-encoded genes, are encoded in the nucleus. Mutations in nuclear-encoded proteins required for mtDNA maintenance is an important cause of neurodegeneration and muscle diseases. The common result of these defects is either mtDNA depletion or accumulation of multiple deletions of mtDNA in postmitotic tissues.
The long-term goal (or vision) of research in my laboratory is to understand in molecular detail how mtDNA is replicated and how this process is regulated in mammalian cells. To this end we use a protein biochemistry approach, which we combine with in vivo verification in cell lines. My group was in 2004 the first to reconstitute mtDNA replication in vitro and we have continued to develop even more elaborate system ever since. In the current application, the major focus is studies of the mitochondrial D-loop region, a triple-stranded structure in the mitochondrial genome. The D-loop functions as a regulatory hub and we will determine how initiation and termination of mtDNA replication is controlled from this region. We will also determine the physical organization of the mtDNA replication machinery at the replication fork and establish how mtDNA deletions, a classical hallmark of human ageing, are formed.
Max ERC Funding
1 999 985 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym DrivenByPollinators
Project Driven by mutualists: how declines in pollinators impact plant communities and ecosystemfunctioning
Researcher (PI) Yann Mats CLOUGH
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), LS8, ERC-2018-COG
Summary Pollinator declines in response to land-use intensification have raised concern about the persistence of plant species dependent on insect pollination, in particular by bees, for their reproduction. Recent empirical studies show that reduced pollinator abundance decreases densities of seedlings of insect-pollinated plants and thereby changes the composition of grassland plant communities. Cascading effects on ecosystem functioning and associated organisms are expected, but to which extent and under which conditions this is the case is yet unexplored. Here, I propose a bold, multi-year, landscape-scale experimental assessment of the extent of pollinator-driven plant community changes, their consequences for associated organisms and important ecosystem functions, and their likely contingency on other factors (soil fertility, herbivory).
Specifically I will:
(1) Set up a network of long-term research plots in landscapes differing in pollinator abundance to measure the changes in plant reproduction over successive years, and assessing experimentally how herbivory and soil fertility mediate these effects.
(2) Explore the individual processes linking pollinators, plant communities and ecosystem functioning using long-term experiments controlling pollinator, herbivore and nutrient availability, focusing on a sample of plant species covering both the dominant species and a diversity of functional traits.
(3) Assess the context-dependence of pollinator-mediated plant community determination by building and applying process-based models based on observational and experimental data, and combine with existing spatially-explicit pollinator models to demonstrate the applicability to assess agri-environmental measures.
This powerful blend of complementary approaches will for the first time shed light on the cornerstone role of this major mutualism in maintaining diverse communities and the functions they support, and pinpoint the risks threatening them and the need for mitigation.
Summary
Pollinator declines in response to land-use intensification have raised concern about the persistence of plant species dependent on insect pollination, in particular by bees, for their reproduction. Recent empirical studies show that reduced pollinator abundance decreases densities of seedlings of insect-pollinated plants and thereby changes the composition of grassland plant communities. Cascading effects on ecosystem functioning and associated organisms are expected, but to which extent and under which conditions this is the case is yet unexplored. Here, I propose a bold, multi-year, landscape-scale experimental assessment of the extent of pollinator-driven plant community changes, their consequences for associated organisms and important ecosystem functions, and their likely contingency on other factors (soil fertility, herbivory).
Specifically I will:
(1) Set up a network of long-term research plots in landscapes differing in pollinator abundance to measure the changes in plant reproduction over successive years, and assessing experimentally how herbivory and soil fertility mediate these effects.
(2) Explore the individual processes linking pollinators, plant communities and ecosystem functioning using long-term experiments controlling pollinator, herbivore and nutrient availability, focusing on a sample of plant species covering both the dominant species and a diversity of functional traits.
(3) Assess the context-dependence of pollinator-mediated plant community determination by building and applying process-based models based on observational and experimental data, and combine with existing spatially-explicit pollinator models to demonstrate the applicability to assess agri-environmental measures.
This powerful blend of complementary approaches will for the first time shed light on the cornerstone role of this major mutualism in maintaining diverse communities and the functions they support, and pinpoint the risks threatening them and the need for mitigation.
Max ERC Funding
1 998 842 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym EXCHANGE
Project Dynamic Complexes and Allosteric Regulation of Small Molecule Transporters
Researcher (PI) David DREW
Host Institution (HI) STOCKHOLMS UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), LS1, ERC-2018-COG
Summary Solute Carrier (SLC) transporters mediate the translocation of substrates across membranes and after GPCRs represent the second-largest fraction of the human membrane proteome. SLC transporters are critical to cell homeostasis, which is reflected in the fact that more than a quarter is associated with Mendelian disease. Despite a few exceptions, however, they have been under-utilized as drug targets and most of the mechanistic understanding has been derived from bacterial homologues of these medically important proteins. In addition to subtle differences, bacterial homologues will not enable us to establish how the activities of many SLC transporters are allosterically regulated through the binding of accessory factors, e.g., hormones, to their non-membranous globular domains. Understanding the mechanisms by which their activities can be allosterically regulated through these complex and dynamic assembles is critical to human physiology and important for future drug design.
Our model system is a family of transporters known as sodium/proton exchangers (NHEs), which exchange sodium for protons across membranes to aid many fundamental processes in the cell. NHEs are important to the cell cycle, cell proliferation, cell migration and vesicle trafficking and are associated with a wide-spectrum of diseases. Their diverse portfolio is connected to the importance of pH homeostasis, and the binding of many different factors to a large, globular cytosolic domain exquisitely regulates them. To date, we have no structural information for any of the NHE’s, functional assays in liposomes are lacking, and many interaction partners are yet to be validated by in vitro studies. Determining the structure, dynamics, and allosteric regulation of NHEs will be an enormous challenge. However, we envisage that by achieving our objectives, we will reveal important mechanistic insights relevant not just to NHEs, but to many types of SLC transporters.
Summary
Solute Carrier (SLC) transporters mediate the translocation of substrates across membranes and after GPCRs represent the second-largest fraction of the human membrane proteome. SLC transporters are critical to cell homeostasis, which is reflected in the fact that more than a quarter is associated with Mendelian disease. Despite a few exceptions, however, they have been under-utilized as drug targets and most of the mechanistic understanding has been derived from bacterial homologues of these medically important proteins. In addition to subtle differences, bacterial homologues will not enable us to establish how the activities of many SLC transporters are allosterically regulated through the binding of accessory factors, e.g., hormones, to their non-membranous globular domains. Understanding the mechanisms by which their activities can be allosterically regulated through these complex and dynamic assembles is critical to human physiology and important for future drug design.
Our model system is a family of transporters known as sodium/proton exchangers (NHEs), which exchange sodium for protons across membranes to aid many fundamental processes in the cell. NHEs are important to the cell cycle, cell proliferation, cell migration and vesicle trafficking and are associated with a wide-spectrum of diseases. Their diverse portfolio is connected to the importance of pH homeostasis, and the binding of many different factors to a large, globular cytosolic domain exquisitely regulates them. To date, we have no structural information for any of the NHE’s, functional assays in liposomes are lacking, and many interaction partners are yet to be validated by in vitro studies. Determining the structure, dynamics, and allosteric regulation of NHEs will be an enormous challenge. However, we envisage that by achieving our objectives, we will reveal important mechanistic insights relevant not just to NHEs, but to many types of SLC transporters.
Max ERC Funding
1 999 875 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym FASDEM
Project Failing and Successful Sequences of Democratization
Researcher (PI) Staffan I. LINDBERG
Host Institution (HI) GOETEBORGS UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), SH2, ERC-2016-COG
Summary The study of democratization lies at the center of political science and is increasingly important in economics, sociology, and history, and has become a central foreign policy objective. Yet, there is little conclusive evidence about in particular endogenous sequences of democratization critical to our ability to provide sound policy advise. FASDEM promises to revolutionize our understanding of the trajectories that fail to lead to democracy, and the pathways that are successful, by addressing two key questions: Which are the failing versus successful sequences of democratization? What are the determining causal relationships in these sequences?
Critical is the just finalized Varieties of Democracy (V-Dem) dataset including some 350 indicators, 34 component-indices, and five main indices of varieties of democracy from 1900 to the present for 173countries – about 15 million data points on democracy. FASDEM, if funded, will use this data capitalizing on a set of novel analytical approaches, tools, and adaptations of modeling from evolutionary biology developed by a research team in a related, project, that together can establish sequences between sets of hundreds of ordinal variables. Under the second objective, FASDEM will take a step further developing upon the latest statistical methodologies of establishing causal identification in observational data, and use these to test each step of such manifest sequences. FASDEM will make a radical departure from the crude and “correlational” paradigm in democratization studies to detail and explain failing and successful sequences of democratization for the first time.
Summary
The study of democratization lies at the center of political science and is increasingly important in economics, sociology, and history, and has become a central foreign policy objective. Yet, there is little conclusive evidence about in particular endogenous sequences of democratization critical to our ability to provide sound policy advise. FASDEM promises to revolutionize our understanding of the trajectories that fail to lead to democracy, and the pathways that are successful, by addressing two key questions: Which are the failing versus successful sequences of democratization? What are the determining causal relationships in these sequences?
Critical is the just finalized Varieties of Democracy (V-Dem) dataset including some 350 indicators, 34 component-indices, and five main indices of varieties of democracy from 1900 to the present for 173countries – about 15 million data points on democracy. FASDEM, if funded, will use this data capitalizing on a set of novel analytical approaches, tools, and adaptations of modeling from evolutionary biology developed by a research team in a related, project, that together can establish sequences between sets of hundreds of ordinal variables. Under the second objective, FASDEM will take a step further developing upon the latest statistical methodologies of establishing causal identification in observational data, and use these to test each step of such manifest sequences. FASDEM will make a radical departure from the crude and “correlational” paradigm in democratization studies to detail and explain failing and successful sequences of democratization for the first time.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-03-01, End date: 2023-02-28
Project acronym MUSES
Project Towards middle-range theories of the co-evolutionary dynamics of multi-level social-ecological systems
Researcher (PI) Maja Schlueter
Host Institution (HI) STOCKHOLMS UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), SH3, ERC-2015-CoG
Summary Humans have the capacity to change the biosphere from local to global scales while at the same time fundamentally depending on a functioning biosphere for their well-being. Moreover human societies are increasingly affected by global change and adapting to it in multiple ways. These interdependencies give rise to non-linear, cross-scale dynamics that pose significant challenges for analysis and governance of social-ecological systems (SES). In view of the need for societal transformations towards sustainability is the identification of mechanisms of change in SES an urgent and cutting-edge research frontier. This project aims to develop new methodologies and middle-range theories of the dynamics of SES. It will take the nature of SES as complex adaptive systems into account by developing a mechanism-based understanding of change in SES as it arises from micro-level interactions within complex networks of actors and ecosystems. Particular emphasis will be put on emergent and top-down cross-scale interactions.
To this end we will develop dynamic multi-level models using agent-based and mathematical modeling approaches. Model development will be based on a typology of cross-scale interactions, theories from the natural and social sciences and empirical evidence from marine and terrestrial SES. We will combine stylized with empirically-based models and cross-case comparison to develop a typology of social-ecological configurations of the long-term persistence of SES and their capacity to change. Knowledge integration across disciplines and the development of integrative frameworks and approaches will be supported by procedures to bridge different ontological and epistemological foundations. The project will advance sustainability science by providing new methods for modeling multi-level SES and cross-scale interactions, and approaches to identify and include critical social-ecological interactions, particularly human adaptive responses, into models of SES.
Summary
Humans have the capacity to change the biosphere from local to global scales while at the same time fundamentally depending on a functioning biosphere for their well-being. Moreover human societies are increasingly affected by global change and adapting to it in multiple ways. These interdependencies give rise to non-linear, cross-scale dynamics that pose significant challenges for analysis and governance of social-ecological systems (SES). In view of the need for societal transformations towards sustainability is the identification of mechanisms of change in SES an urgent and cutting-edge research frontier. This project aims to develop new methodologies and middle-range theories of the dynamics of SES. It will take the nature of SES as complex adaptive systems into account by developing a mechanism-based understanding of change in SES as it arises from micro-level interactions within complex networks of actors and ecosystems. Particular emphasis will be put on emergent and top-down cross-scale interactions.
To this end we will develop dynamic multi-level models using agent-based and mathematical modeling approaches. Model development will be based on a typology of cross-scale interactions, theories from the natural and social sciences and empirical evidence from marine and terrestrial SES. We will combine stylized with empirically-based models and cross-case comparison to develop a typology of social-ecological configurations of the long-term persistence of SES and their capacity to change. Knowledge integration across disciplines and the development of integrative frameworks and approaches will be supported by procedures to bridge different ontological and epistemological foundations. The project will advance sustainability science by providing new methods for modeling multi-level SES and cross-scale interactions, and approaches to identify and include critical social-ecological interactions, particularly human adaptive responses, into models of SES.
Max ERC Funding
1 969 599 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
Project acronym REBOOT
Project Releasing the brakes on adult plasticity
Researcher (PI) Martin Loevden
Host Institution (HI) KAROLINSKA INSTITUTET
Country Sweden
Call Details Consolidator Grant (CoG), SH4, ERC-2013-CoG
Summary Age-related cognitive impairments compromise the functional capacity of aging individuals, and create major individual and societal costs. Developing means for preserving and restoring cognitive functioning in old age is therefore of great importance. Age-related cognitive impairments have a complex and multifactorial etiology. Pharmaceutical approaches to prevention and treatment have therefore been unsuccessful, and searching for non-pharmaceutical approaches is important. Results of cognitive training studies have so far been disappointing. I hypothesize that the reason for this is that plasticity is functionally inhibited after normal childhood development. Plasticity is then further reduced in aging due to negative brain changes. In this sense, past studies on the effects of cognitive training in adulthood and old age have, so to speak, attempted to push a car that has the brakes on. In a series of experimental studies on humans, my research team will discover feasible ways to release inhibitory brakes on adult plasticity, develop routes to attenuate age-related negative effects on plasticity, and uncover the neural mediators of training-related change in performance, so that the effects of cognitive training can be increased and better understood. Outcome variables include measures of brain function, volume, and integrity acquired using high-resolution magnetic resonance imaging, and up-to-date measures of cognitive performance. Experimental effects on these measures will be evaluated using structural equation models suitable for analyzing repeated measures. This amalgamation of state-of-the-art methodology in the neurosciences and the behavioral sciences bolsters the uniqueness of this research program, which will enlighten the mechanisms of plasticity at neuronal and behavioral levels of analysis. The resulting insights will pave the way for effective rehabilitation of several neurological conditions and for reducing age-associated cognitive impairments.
Summary
Age-related cognitive impairments compromise the functional capacity of aging individuals, and create major individual and societal costs. Developing means for preserving and restoring cognitive functioning in old age is therefore of great importance. Age-related cognitive impairments have a complex and multifactorial etiology. Pharmaceutical approaches to prevention and treatment have therefore been unsuccessful, and searching for non-pharmaceutical approaches is important. Results of cognitive training studies have so far been disappointing. I hypothesize that the reason for this is that plasticity is functionally inhibited after normal childhood development. Plasticity is then further reduced in aging due to negative brain changes. In this sense, past studies on the effects of cognitive training in adulthood and old age have, so to speak, attempted to push a car that has the brakes on. In a series of experimental studies on humans, my research team will discover feasible ways to release inhibitory brakes on adult plasticity, develop routes to attenuate age-related negative effects on plasticity, and uncover the neural mediators of training-related change in performance, so that the effects of cognitive training can be increased and better understood. Outcome variables include measures of brain function, volume, and integrity acquired using high-resolution magnetic resonance imaging, and up-to-date measures of cognitive performance. Experimental effects on these measures will be evaluated using structural equation models suitable for analyzing repeated measures. This amalgamation of state-of-the-art methodology in the neurosciences and the behavioral sciences bolsters the uniqueness of this research program, which will enlighten the mechanisms of plasticity at neuronal and behavioral levels of analysis. The resulting insights will pave the way for effective rehabilitation of several neurological conditions and for reducing age-associated cognitive impairments.
Max ERC Funding
1 918 070 €
Duration
Start date: 2014-07-01, End date: 2019-06-30
Project acronym SMILE
Project Single Molecule Investigations in Living E. coli
Researcher (PI) Per Johan Sven Elf
Host Institution (HI) UPPSALA UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), LS2, ERC-2013-CoG
Summary The overall ambition is to make intracellular measurements that bridge the gap between quantitative physical models and biological observations, in order to identify and resolve inconsistencies in our current understanding of life at the molecular level.
We are particularly interested in answering fundamental questions about how the molecules that regulate gene expression and DNA replication operate in the intracellular environment. These questions include how transcription factors and RNA polymerases have evolved to rapidly find and bind their specific binding sites on chromosomal DNA, how the initiation of DNA replication is coordinated with cell growth, how cells can filter out leakage during replication of repressed genes, and other questions related to how the physical limitations of molecular interactions constrain cellular regulation.
Answering these questions requires better methods to study intracellular kinetics at high spatial and temporal resolution. For this purpose we will develop single-molecule methods to probe kinetics without perturbing the system. The project depends on development in five different fields (1) new labeling methods using unnatural amino acids, (2) new hardware solutions for single molecule tracking, (3) new microfluidic designs for controlled growth conditions and image analysis, (4) new computational tools to extract the maximal amount of information from many short single molecule trajectories and (5) accurate ways of computing synthetic microscopy images.
In addressing the specific questions stated above the experiments are necessarily combined with biophysical modeling that makes it possible to tell if the experimental results are expected from the previously known interactions and physical limitations due to for example stochasticity, slow diffusion and confined geometries. Overall the project is unique in its ambition to make a physically consistent quantitative description of central processes of life at the molecular level.
Summary
The overall ambition is to make intracellular measurements that bridge the gap between quantitative physical models and biological observations, in order to identify and resolve inconsistencies in our current understanding of life at the molecular level.
We are particularly interested in answering fundamental questions about how the molecules that regulate gene expression and DNA replication operate in the intracellular environment. These questions include how transcription factors and RNA polymerases have evolved to rapidly find and bind their specific binding sites on chromosomal DNA, how the initiation of DNA replication is coordinated with cell growth, how cells can filter out leakage during replication of repressed genes, and other questions related to how the physical limitations of molecular interactions constrain cellular regulation.
Answering these questions requires better methods to study intracellular kinetics at high spatial and temporal resolution. For this purpose we will develop single-molecule methods to probe kinetics without perturbing the system. The project depends on development in five different fields (1) new labeling methods using unnatural amino acids, (2) new hardware solutions for single molecule tracking, (3) new microfluidic designs for controlled growth conditions and image analysis, (4) new computational tools to extract the maximal amount of information from many short single molecule trajectories and (5) accurate ways of computing synthetic microscopy images.
In addressing the specific questions stated above the experiments are necessarily combined with biophysical modeling that makes it possible to tell if the experimental results are expected from the previously known interactions and physical limitations due to for example stochasticity, slow diffusion and confined geometries. Overall the project is unique in its ambition to make a physically consistent quantitative description of central processes of life at the molecular level.
Max ERC Funding
2 398 823 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym UltimateCOMPASS
Project Navigating the most challenging habitats on earth:unravelling the architecture of a universal compass system
Researcher (PI) Marie DACKE
Host Institution (HI) LUNDS UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), LS8, ERC-2018-COG
Summary When lost in the desert at night, or in dense forests, people tend to walk in circles. This is because the seemingly simple act of walking in a straight line involves a complex interplay of various sensory modalities, the motor system and cognition. A ball-rolling dung beetle released in the same type of uncharted territory, does not walk in circles, but rather keeps steadfastly to a chosen bearing. The main goal of this project is unravel the sensory and neuronal architecture of the newly discovered ‘snapshot compass’, that supports orientation over all continents and terrestrial habitats on earth (except Antarctica). This goal will be realized through a fusion of biology, bio-informatics and mathematics.
A quickly growing pool of studies indicates that neuronal networks are modulated in a context-dependent manner. Therefore, to truly understand how this compass works, and to formulate the core computational algorithms underlying this remarkable system, I aim to obtain the first ever brain recordings from the compass of a freely orienting insect. Is this possible? Certainly! But only in an animal with a robust orientation behaviour, and that is strong enough to carry a little backpack of electronics. The large dung-beetles, with their easily manipulated orientation behavior, offers a unique opportunity to attain this holy grail of neuroethology.
The beetle’s compass makes use of a large range of celestial cues, which can vary drastically in availability and strength. While the challenge of cue integration has been solved effectively in the compass system of the beetles, it remains a key problem within the field of cognition and perception, as well as for the design of artificial intelligence systems. Taken together, almost two decades of studies of the dung beetle compass system have paved the way for this timely and unique opportunity, that will impact the advancement of science well outside the field of biology.
Summary
When lost in the desert at night, or in dense forests, people tend to walk in circles. This is because the seemingly simple act of walking in a straight line involves a complex interplay of various sensory modalities, the motor system and cognition. A ball-rolling dung beetle released in the same type of uncharted territory, does not walk in circles, but rather keeps steadfastly to a chosen bearing. The main goal of this project is unravel the sensory and neuronal architecture of the newly discovered ‘snapshot compass’, that supports orientation over all continents and terrestrial habitats on earth (except Antarctica). This goal will be realized through a fusion of biology, bio-informatics and mathematics.
A quickly growing pool of studies indicates that neuronal networks are modulated in a context-dependent manner. Therefore, to truly understand how this compass works, and to formulate the core computational algorithms underlying this remarkable system, I aim to obtain the first ever brain recordings from the compass of a freely orienting insect. Is this possible? Certainly! But only in an animal with a robust orientation behaviour, and that is strong enough to carry a little backpack of electronics. The large dung-beetles, with their easily manipulated orientation behavior, offers a unique opportunity to attain this holy grail of neuroethology.
The beetle’s compass makes use of a large range of celestial cues, which can vary drastically in availability and strength. While the challenge of cue integration has been solved effectively in the compass system of the beetles, it remains a key problem within the field of cognition and perception, as well as for the design of artificial intelligence systems. Taken together, almost two decades of studies of the dung beetle compass system have paved the way for this timely and unique opportunity, that will impact the advancement of science well outside the field of biology.
Max ERC Funding
1 994 225 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
