Project acronym ADAPT
Project Origins and factors governing adaptation: Insights from experimental evolution and population genomic data
Researcher (PI) Thomas, Martin Jean Bataillon
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary "I propose a systematic study of the type of genetic variation enabling adaptation and factors that limit rates of adaptation in natural populations. New methods will be developed for analysing data from experimental evolution and population genomics. The methods will be applied to state of the art data from both fields. Adaptation is generated by natural selection sieving through heritable variation. Examples of adaptation are available from the fossil record and from extant populations. Genomic studies have supplied many instances of genomic regions exhibiting footprint of natural selection favouring new variants. Despite ample proof that adaptation happens, we know little about beneficial mutations– the raw stuff enabling adaptation. Is adaptation mediated by genetic variation pre-existing in the population, or by variation supplied de novo through mutations? We know even less about what factors limit rates of adaptation. Answers to these questions are crucial for Evolutionary Biology, but also for believable quantifications of the evolutionary potential of populations. Population genetic theory makes predictions and allows inference from the patterns of polymorphism within species and divergence between species. Yet models specifying the fitness effects of mutations are often missing. Fitness landscape models will be mobilized to fill this gap and develop methods for inferring the distribution of fitness effects and factors governing rates of adaptation. Insights into the processes underlying adaptation will thus be gained from experimental evolution and population genomics data. The applicability of insights gained from experimental evolution to comprehend adaptation in nature will be scrutinized. We will unite two very different approaches for studying adaptation. The project will boost our understanding of how selection shapes genomes and open the way for further quantitative tests of theories of adaptation."
Summary
"I propose a systematic study of the type of genetic variation enabling adaptation and factors that limit rates of adaptation in natural populations. New methods will be developed for analysing data from experimental evolution and population genomics. The methods will be applied to state of the art data from both fields. Adaptation is generated by natural selection sieving through heritable variation. Examples of adaptation are available from the fossil record and from extant populations. Genomic studies have supplied many instances of genomic regions exhibiting footprint of natural selection favouring new variants. Despite ample proof that adaptation happens, we know little about beneficial mutations– the raw stuff enabling adaptation. Is adaptation mediated by genetic variation pre-existing in the population, or by variation supplied de novo through mutations? We know even less about what factors limit rates of adaptation. Answers to these questions are crucial for Evolutionary Biology, but also for believable quantifications of the evolutionary potential of populations. Population genetic theory makes predictions and allows inference from the patterns of polymorphism within species and divergence between species. Yet models specifying the fitness effects of mutations are often missing. Fitness landscape models will be mobilized to fill this gap and develop methods for inferring the distribution of fitness effects and factors governing rates of adaptation. Insights into the processes underlying adaptation will thus be gained from experimental evolution and population genomics data. The applicability of insights gained from experimental evolution to comprehend adaptation in nature will be scrutinized. We will unite two very different approaches for studying adaptation. The project will boost our understanding of how selection shapes genomes and open the way for further quantitative tests of theories of adaptation."
Max ERC Funding
1 159 857 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym ANINAN
Project An Intersectional Analysis of Ancient Jewish Travel Narratives
Researcher (PI) Elisa Katariina UUSIMaeKI
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), SH5, ERC-2020-STG
Summary ANINAN investigates literary and cultural representations of travel and mobility – the often temporary move of a person from her or his home to another location – in ancient Israelite/Jewish narratives, including selected texts of the Hebrew Bible and other Jewish writings from the Hellenistic and early Roman eras (ca. 300 BCE – 100 CE). The sources, which originate from different parts of the Mediterranean region, are written or preserved in Hebrew, Aramaic, Greek, Latin, and Ge’ez.
The aim is to understand how human mobility was perceived and/or imagined in Jewish antiquity, including its agents, motives, and outcomes. The main objectives are: (1) to produce a series of case-studies that illustrate the portrayal of human mobility and its social confines in Israelite/Jewish literature; and (2) to compare and theorize the cultural representations of travel in an intersectional frame and, as a result, to provide a ground-breaking interpretative framework for the study of mobility in texts from the human past. The selected intersectional approach is novel and specifically unearths questions of power and social stratification that evidently pertain to (in)voluntary forms of mobility, including the individual profile of the traveller and the social realities that prompted, enabled, or compelled her or his travel in the first place.
The challenge is that we know nothing about the power dynamics of ancient Israelite/Jewish travel accounts. They are expected to reveal striking intersectional concerns, highlighting the complexity of human phenomena such as mobility. While multiple ‘categories of difference’ characterize the travelling agents, mobility also affects and shapes these categories, e.g., by leading the agent to negotiate, refine, or recreate aspects of her or his identity. The narratives also illustrate encounters between the Israelites/Jews and ‘others’, which results in a new understanding of cultural interaction in the ancient eastern Mediterranean.
Summary
ANINAN investigates literary and cultural representations of travel and mobility – the often temporary move of a person from her or his home to another location – in ancient Israelite/Jewish narratives, including selected texts of the Hebrew Bible and other Jewish writings from the Hellenistic and early Roman eras (ca. 300 BCE – 100 CE). The sources, which originate from different parts of the Mediterranean region, are written or preserved in Hebrew, Aramaic, Greek, Latin, and Ge’ez.
The aim is to understand how human mobility was perceived and/or imagined in Jewish antiquity, including its agents, motives, and outcomes. The main objectives are: (1) to produce a series of case-studies that illustrate the portrayal of human mobility and its social confines in Israelite/Jewish literature; and (2) to compare and theorize the cultural representations of travel in an intersectional frame and, as a result, to provide a ground-breaking interpretative framework for the study of mobility in texts from the human past. The selected intersectional approach is novel and specifically unearths questions of power and social stratification that evidently pertain to (in)voluntary forms of mobility, including the individual profile of the traveller and the social realities that prompted, enabled, or compelled her or his travel in the first place.
The challenge is that we know nothing about the power dynamics of ancient Israelite/Jewish travel accounts. They are expected to reveal striking intersectional concerns, highlighting the complexity of human phenomena such as mobility. While multiple ‘categories of difference’ characterize the travelling agents, mobility also affects and shapes these categories, e.g., by leading the agent to negotiate, refine, or recreate aspects of her or his identity. The narratives also illustrate encounters between the Israelites/Jews and ‘others’, which results in a new understanding of cultural interaction in the ancient eastern Mediterranean.
Max ERC Funding
1 368 977 €
Duration
Start date: 2021-02-01, End date: 2026-01-31
Project acronym BIOMEMOS
Project Higher order structure and function of biomembranes
Researcher (PI) Poul Nissen
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Advanced Grant (AdG), LS1, ERC-2009-AdG
Summary The biomembrane is a prerequisite of life. It enables the cell to maintain a controlled environment and to establish electrochemical gradients as rapidly accessible energy stores. Biomembranes also provide scaffold for organisation and spatial definition of signal transmission in the cell. Crystal structures of membrane proteins are determined with an increasing pace. Along with functional studies integral studies of individual membrane proteins are now widely implemented. The BIOMEMOS proposal goes a step further and approaches the function of the biomembrane at the higher level of membrane protein complexes. Through a combination of X-ray crystallography, electrophysiology, general biochemistry, biophysics and bioinformatics and including also the application of single-particle cryo-EM and small-angle X-ray scattering, the structure and function of membrane protein complexes of key importance in life will be investigated. The specific targets for investigation in this proposal include: 1) higher-order complexes of P-type ATPase pumps such as signalling complexes of Na+,K+-ATPase, and 2) development of methods for structural studies of membrane protein complexes Based on my unique track record in structural studies of large, difficult structures (ribosomes and membrane proteins) in the setting of a thriving research community in structural biology and biomembrane research in Aarhus provides a critical momentum for a long-term activity. The activity will take advantage of the new possibilities offered by synchrotron sources in Europe. Furthermore, a single-particle cryo-EM research group formed on my initiative in Aarhus, and a well-established small-angle X-ray scattering community provides for an optimal setting through multiple cues in structural biology and functional studies
Summary
The biomembrane is a prerequisite of life. It enables the cell to maintain a controlled environment and to establish electrochemical gradients as rapidly accessible energy stores. Biomembranes also provide scaffold for organisation and spatial definition of signal transmission in the cell. Crystal structures of membrane proteins are determined with an increasing pace. Along with functional studies integral studies of individual membrane proteins are now widely implemented. The BIOMEMOS proposal goes a step further and approaches the function of the biomembrane at the higher level of membrane protein complexes. Through a combination of X-ray crystallography, electrophysiology, general biochemistry, biophysics and bioinformatics and including also the application of single-particle cryo-EM and small-angle X-ray scattering, the structure and function of membrane protein complexes of key importance in life will be investigated. The specific targets for investigation in this proposal include: 1) higher-order complexes of P-type ATPase pumps such as signalling complexes of Na+,K+-ATPase, and 2) development of methods for structural studies of membrane protein complexes Based on my unique track record in structural studies of large, difficult structures (ribosomes and membrane proteins) in the setting of a thriving research community in structural biology and biomembrane research in Aarhus provides a critical momentum for a long-term activity. The activity will take advantage of the new possibilities offered by synchrotron sources in Europe. Furthermore, a single-particle cryo-EM research group formed on my initiative in Aarhus, and a well-established small-angle X-ray scattering community provides for an optimal setting through multiple cues in structural biology and functional studies
Max ERC Funding
2 444 180 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
Project acronym BOSADMIX
Project Genetic admixture and its impact on domestication in the Bos genus: a model for genetic improvement of livestock
Researcher (PI) Rasmus Heller
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS8, ERC-2019-STG
Summary Background
Genetic exchange across species boundaries is emerging as a much more common phenomenon than previously assumed. This introduces potentially adaptive genetic variation into recipient populations. Such interspecies admixture is believed to have played an important role in domestication events, particularly in members of the Bos genus, which uniquely harbours no fewer than five independently domesticated lineages. Understanding these independent, yet reticulated evolutionary events is of fundamental interest for managing the genetic resources of domestic and wild bovids.
Objectives
I propose to investigate the role of interspecies admixture in domestication through four linked topics. The first is to systematically map the interspecies admixture among seven Asian Bos species, and to determine whether introgressed elements have been beneficial to the recipient populations. The second is to identify genes that have been under strong selection in each independent domestication process. The third is to link adaptively introgressed genomic elements with phenotypic effects. The fourth will address the future of genetic resources in all Asian Bos.
Methods
The project will bring together a large set of complete genomes and use a combination of population genetic and comparative genomic methods. Phenotypic data and experiments will be performed to validate the phenotypic effects of key introgressed elements and genes under selection during the domestication process.
Expected outcome and importance
The project will improve our understanding of the evolutionary dynamics of genetic elements that cross the species barrier, in particular the interplay between admixture and the domestication process. It will also provide important insights into the domestication process itself. A joint understanding of these processes is crucial for assessing which types of foreign genetic elements that can be useful for genetic improvement of domestic species.
Summary
Background
Genetic exchange across species boundaries is emerging as a much more common phenomenon than previously assumed. This introduces potentially adaptive genetic variation into recipient populations. Such interspecies admixture is believed to have played an important role in domestication events, particularly in members of the Bos genus, which uniquely harbours no fewer than five independently domesticated lineages. Understanding these independent, yet reticulated evolutionary events is of fundamental interest for managing the genetic resources of domestic and wild bovids.
Objectives
I propose to investigate the role of interspecies admixture in domestication through four linked topics. The first is to systematically map the interspecies admixture among seven Asian Bos species, and to determine whether introgressed elements have been beneficial to the recipient populations. The second is to identify genes that have been under strong selection in each independent domestication process. The third is to link adaptively introgressed genomic elements with phenotypic effects. The fourth will address the future of genetic resources in all Asian Bos.
Methods
The project will bring together a large set of complete genomes and use a combination of population genetic and comparative genomic methods. Phenotypic data and experiments will be performed to validate the phenotypic effects of key introgressed elements and genes under selection during the domestication process.
Expected outcome and importance
The project will improve our understanding of the evolutionary dynamics of genetic elements that cross the species barrier, in particular the interplay between admixture and the domestication process. It will also provide important insights into the domestication process itself. A joint understanding of these processes is crucial for assessing which types of foreign genetic elements that can be useful for genetic improvement of domestic species.
Max ERC Funding
1 499 275 €
Duration
Start date: 2020-02-01, End date: 2025-01-31
Project acronym C-MORPH
Project Noninvasive cell specific morphometry in neuroinflammation and degeneration
Researcher (PI) Henrik LUNDELL
Host Institution (HI) REGION HOVEDSTADEN
Country Denmark
Call Details Starting Grant (StG), LS7, ERC-2018-STG
Summary Brain structure determines function. Disentangling regional microstructural properties and understanding how these properties constitute brain function is a central goal of neuroimaging of the human brain and a key prerequisite for a mechanistic understanding of brain diseases and their treatment. Using magnetic resonance (MR) imaging, previous research has established links between regional brain microstructure and inter-individual variation in brain function, but this line of research has been limited by the non-specificity of MR-derived markers. This hampers the application of MR imaging as a tool to identify specific fingerprints of the underlying disease process.
Exploiting state-of-the-art ultra-high field MR imaging techniques, I have recently developed two independent spectroscopic MR methods that have the potential to tackle this challenge: Powder averaged diffusion weighted spectroscopy (PADWS) can provide an unbiased marker for cell specific structural degeneration, and Spectrally tuned gradient trajectories (STGT) can isolate cell shape and size. In this project, I will harness these innovations for MR-based precision medicine. I will advance PADWS and STGT methodology on state-of-the-art MR hardware and harvest the synergy of these methods to realize Cell-specific in-vivo MORPHOMETRY (C-MORPH) of the intact human brain. I will establish novel MR read-outs and analyses to derive cell-type specific tissue properties in the healthy and diseased brain and validate them with the help of a strong translational experimental framework, including histological validation. Once validated, the experimental methods and analyses will be simplified and adapted to provide clinically applicable tools. This will push the frontiers of MR-based personalized medicine, guiding therapeutic decisions by providing sensitive probes of cell-specific microstructural changes caused by inflammation, neurodegeneration or treatment response.
Summary
Brain structure determines function. Disentangling regional microstructural properties and understanding how these properties constitute brain function is a central goal of neuroimaging of the human brain and a key prerequisite for a mechanistic understanding of brain diseases and their treatment. Using magnetic resonance (MR) imaging, previous research has established links between regional brain microstructure and inter-individual variation in brain function, but this line of research has been limited by the non-specificity of MR-derived markers. This hampers the application of MR imaging as a tool to identify specific fingerprints of the underlying disease process.
Exploiting state-of-the-art ultra-high field MR imaging techniques, I have recently developed two independent spectroscopic MR methods that have the potential to tackle this challenge: Powder averaged diffusion weighted spectroscopy (PADWS) can provide an unbiased marker for cell specific structural degeneration, and Spectrally tuned gradient trajectories (STGT) can isolate cell shape and size. In this project, I will harness these innovations for MR-based precision medicine. I will advance PADWS and STGT methodology on state-of-the-art MR hardware and harvest the synergy of these methods to realize Cell-specific in-vivo MORPHOMETRY (C-MORPH) of the intact human brain. I will establish novel MR read-outs and analyses to derive cell-type specific tissue properties in the healthy and diseased brain and validate them with the help of a strong translational experimental framework, including histological validation. Once validated, the experimental methods and analyses will be simplified and adapted to provide clinically applicable tools. This will push the frontiers of MR-based personalized medicine, guiding therapeutic decisions by providing sensitive probes of cell-specific microstructural changes caused by inflammation, neurodegeneration or treatment response.
Max ERC Funding
1 498 811 €
Duration
Start date: 2018-12-01, End date: 2023-11-30
Project acronym CASINO
Project Carbohydrate signals controlling nodulation
Researcher (PI) Jens Stougaard Jensen
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Advanced Grant (AdG), LS3, ERC-2010-AdG_20100317
Summary Mechanisms governing interaction between multicellular organisms and microbes are central for understanding pathogenesis, symbiosis and the function of ecosystems. We propose to address these mechanisms by pioneering an interdisciplinary approach for understanding cellular signalling, response processes and organ development. The challenge is to determine factors synchronising three processes, organogenesis, infection thread formation and bacterial infection, running in parallel to build a root nodule hosting symbiotic bacteria. We aim to exploit the unique possibilities for analysing endocytosis of bacteria in model legumes and to develop genomic, genetic and biological chemistry tools to break new ground in our understanding of carbohydrates in plant development and plant-microbe interaction. Surface exposed rhizobial polysaccharides play a crucial but poorly understood role in infection thread formation and rhizobial invasion resulting in endocytosis. We will undertake an integrated functional characterisation of receptor-ligand mechanisms mediating recognition of secreted polysaccharides and subsequent signal amplification. So far progress in this field has been limited by the complex nature of carbohydrate polymers, lack of a suitable experimental model system where both partners in an interaction could be manipulated and lack of corresponding methods for carbohydrate synthesis, analysis and interaction studies. In this context our legume model system and the discovery that the legume Nod-factor receptors recognise bacterial lipochitin-oligosaccharide signals at their LysM domains provides a new opportunity. Combined with advanced bioorganic chemistry and nanobioscience approaches this proposal will engage the above mentioned limitations.
Summary
Mechanisms governing interaction between multicellular organisms and microbes are central for understanding pathogenesis, symbiosis and the function of ecosystems. We propose to address these mechanisms by pioneering an interdisciplinary approach for understanding cellular signalling, response processes and organ development. The challenge is to determine factors synchronising three processes, organogenesis, infection thread formation and bacterial infection, running in parallel to build a root nodule hosting symbiotic bacteria. We aim to exploit the unique possibilities for analysing endocytosis of bacteria in model legumes and to develop genomic, genetic and biological chemistry tools to break new ground in our understanding of carbohydrates in plant development and plant-microbe interaction. Surface exposed rhizobial polysaccharides play a crucial but poorly understood role in infection thread formation and rhizobial invasion resulting in endocytosis. We will undertake an integrated functional characterisation of receptor-ligand mechanisms mediating recognition of secreted polysaccharides and subsequent signal amplification. So far progress in this field has been limited by the complex nature of carbohydrate polymers, lack of a suitable experimental model system where both partners in an interaction could be manipulated and lack of corresponding methods for carbohydrate synthesis, analysis and interaction studies. In this context our legume model system and the discovery that the legume Nod-factor receptors recognise bacterial lipochitin-oligosaccharide signals at their LysM domains provides a new opportunity. Combined with advanced bioorganic chemistry and nanobioscience approaches this proposal will engage the above mentioned limitations.
Max ERC Funding
2 399 127 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
Project acronym CHILDGROWTH2CANCER
Project Childhood body size, growth and pubertal timing and the risk of cancer in adulthood
Researcher (PI) Jennifer Lyn Baker
Host Institution (HI) REGION HOVEDSTADEN
Country Denmark
Call Details Starting Grant (StG), LS7, ERC-2011-StG_20101109
Summary The goal of the proposed research is to examine how the independent and combined effects of childhood adiposity (assessed by body mass index [BMI]; kg/m2) height, change in BMI and height, and pubertal timing from the ages of 7 to 13 years are associated with the risk of cancer incidence in adulthood. Greater body size (adipose tissue and different types of lean tissue) reflecting past or ongoing growth may increase the risk of cancer in individuals as greater numbers of proliferating cells increase the risk that mutations leading to the subsequent development of cancer occur. As childhood is a period of growth, it is plausible that it is of particular relevance for the early establishment of the risk of cancer.
Data from the Copenhagen School Health Records Register, which is based on a population of schoolchildren born between 1930-1983 and contains computerised weight and height measurements on >350.000 boys and girls in the capital city of Denmark, as well as data from other cohorts will be used. Survival analysis techniques and the newly developed Dynamic Path Analysis model will be used to examine how body size (BMI and height) at each age from 7 to 13 years as well as change in body size during this period is associated with the risk of multiple forms of cancer in adulthood with a simultaneous exploration of the effects of birth weight and pubertal timing. Additionally, potential effects of childhood and adult health and social circumstances will be investigated in sub-cohorts with this information available.
Results from this research will demonstrate if childhood is a critical period for the establishment of the risk for cancer in adulthood and will lead into mechanistic explorations of the associations at the biological level, investigations into associations between childhood body size and mortality and contribute to developing improved definitions of childhood overweight and obesity that are based upon long-term health outcomes.
Summary
The goal of the proposed research is to examine how the independent and combined effects of childhood adiposity (assessed by body mass index [BMI]; kg/m2) height, change in BMI and height, and pubertal timing from the ages of 7 to 13 years are associated with the risk of cancer incidence in adulthood. Greater body size (adipose tissue and different types of lean tissue) reflecting past or ongoing growth may increase the risk of cancer in individuals as greater numbers of proliferating cells increase the risk that mutations leading to the subsequent development of cancer occur. As childhood is a period of growth, it is plausible that it is of particular relevance for the early establishment of the risk of cancer.
Data from the Copenhagen School Health Records Register, which is based on a population of schoolchildren born between 1930-1983 and contains computerised weight and height measurements on >350.000 boys and girls in the capital city of Denmark, as well as data from other cohorts will be used. Survival analysis techniques and the newly developed Dynamic Path Analysis model will be used to examine how body size (BMI and height) at each age from 7 to 13 years as well as change in body size during this period is associated with the risk of multiple forms of cancer in adulthood with a simultaneous exploration of the effects of birth weight and pubertal timing. Additionally, potential effects of childhood and adult health and social circumstances will be investigated in sub-cohorts with this information available.
Results from this research will demonstrate if childhood is a critical period for the establishment of the risk for cancer in adulthood and will lead into mechanistic explorations of the associations at the biological level, investigations into associations between childhood body size and mortality and contribute to developing improved definitions of childhood overweight and obesity that are based upon long-term health outcomes.
Max ERC Funding
1 199 998 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym CHIPS
Project Effects of Prenatal Exposure to Acrylamide on Health: Prospective Biomarker-Based Studies
Researcher (PI) Marie Pedersen
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS7, ERC-2017-STG
Summary Background: Acrylamide is a chemical formed in many commonly consumed foods and beverages. It is neurotoxic, crosses the placenta and has been associated with restriction of fetal growth in humans. In animals, acrylamide causes heritable mutations, tumors, developmental toxicity, reduced fertility and impaired growth. Therefore, the discovery of acrylamide in food in 2002 raised concern about human health effects worldwide. Still, epidemiological studies are limited and effects on health of prenatal exposure have never been evaluated.
Research gaps: Epidemiological studies have mostly addressed exposure during adulthood, focused on cancer risk in adults, and relied on questionnaires entailing a high degree of exposure misclassification. Biomarker studies on prenatal exposure to acrylamide from diet are critically needed to improve exposure assessment and to determine whether acrylamide leads to major diseases later in life.
Own results: I have first authored a prospective European study showing that prenatal exposure to acrylamide, estimated by measuring hemoglobin adducts in cord blood, was associated with fetal growth restriction, for the first time.
Objectives: To determine the effects of prenatal exposure to acrylamide alone and in combination with other potentially toxic adduct-forming exposures on the health of children and young adults.
Methods: Both well-established and innovative biomarker methods will be used for characterization of prenatal exposure to acrylamide and related toxicants in blood from pregnant women and their offspring in prospective cohort studies with long-term follow-up. Risk of neurological disorders, impaired cognition, disturbed reproductive function and metabolic outcomes such as obesity and diabetes will be evaluated.
Perspectives: CHIPS project will provide a better understanding of the impact of prenatal exposure to acrylamide from diet on human health urgently needed for targeted strategies for the protection of the health.
Summary
Background: Acrylamide is a chemical formed in many commonly consumed foods and beverages. It is neurotoxic, crosses the placenta and has been associated with restriction of fetal growth in humans. In animals, acrylamide causes heritable mutations, tumors, developmental toxicity, reduced fertility and impaired growth. Therefore, the discovery of acrylamide in food in 2002 raised concern about human health effects worldwide. Still, epidemiological studies are limited and effects on health of prenatal exposure have never been evaluated.
Research gaps: Epidemiological studies have mostly addressed exposure during adulthood, focused on cancer risk in adults, and relied on questionnaires entailing a high degree of exposure misclassification. Biomarker studies on prenatal exposure to acrylamide from diet are critically needed to improve exposure assessment and to determine whether acrylamide leads to major diseases later in life.
Own results: I have first authored a prospective European study showing that prenatal exposure to acrylamide, estimated by measuring hemoglobin adducts in cord blood, was associated with fetal growth restriction, for the first time.
Objectives: To determine the effects of prenatal exposure to acrylamide alone and in combination with other potentially toxic adduct-forming exposures on the health of children and young adults.
Methods: Both well-established and innovative biomarker methods will be used for characterization of prenatal exposure to acrylamide and related toxicants in blood from pregnant women and their offspring in prospective cohort studies with long-term follow-up. Risk of neurological disorders, impaired cognition, disturbed reproductive function and metabolic outcomes such as obesity and diabetes will be evaluated.
Perspectives: CHIPS project will provide a better understanding of the impact of prenatal exposure to acrylamide from diet on human health urgently needed for targeted strategies for the protection of the health.
Max ERC Funding
1 499 531 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym CHROMATINREPLICATION
Project How to Replicate Chromatin - Maturation, Timing Control and Stress-Induced Aberrations
Researcher (PI) Anja Groth
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS1, ERC-2011-StG_20101109
Summary Inheritance of DNA sequence and its proper organization into chromatin is fundamental for eukaryotic life. The challenge of propagating genetic and epigenetic information is met in S phase and entails genome-wide disruption and restoration of chromatin coupled to faithful copying of DNA. How specific chromatin structures are restored on new DNA and transmitted through mitotic cell division remains a fundamental question in biology central to understand cell fate and identity.
Chromatin restoration on new DNA involves a complex set of events including nucleosome assembly and remodelling, restoration of marks on DNA and histones, deposition of histone variants and establishment of higher order chromosomal structures including sister-chromatid cohesion. To dissect these fundamental processes and their coordination in time and space with DNA replication, we have developed a novel technology termed nascent chromatin capture (NCC) that provides unique possibility for biochemical and proteomic analysis of chromatin replication in human cells. I propose to apply this innovative cutting-edge technique for a comprehensive characterization of chromatin restoration during DNA replication and to reveal how replication timing and genotoxic stress impact on final chromatin state. This highly topical project brings together the fields of chromatin biology, DNA replication, epigenetics and genome stability and we expect to make groundbreaking discoveries that will improve our understanding of human development, somatic cell reprogramming and complex diseases like cancer.
The proposed research will 1) identify and characterize novel mechanisms in chromatin restoration and 2) address molecularly how replication timing and genotoxic insults influence chromatin maturation and final chromatin state.
Summary
Inheritance of DNA sequence and its proper organization into chromatin is fundamental for eukaryotic life. The challenge of propagating genetic and epigenetic information is met in S phase and entails genome-wide disruption and restoration of chromatin coupled to faithful copying of DNA. How specific chromatin structures are restored on new DNA and transmitted through mitotic cell division remains a fundamental question in biology central to understand cell fate and identity.
Chromatin restoration on new DNA involves a complex set of events including nucleosome assembly and remodelling, restoration of marks on DNA and histones, deposition of histone variants and establishment of higher order chromosomal structures including sister-chromatid cohesion. To dissect these fundamental processes and their coordination in time and space with DNA replication, we have developed a novel technology termed nascent chromatin capture (NCC) that provides unique possibility for biochemical and proteomic analysis of chromatin replication in human cells. I propose to apply this innovative cutting-edge technique for a comprehensive characterization of chromatin restoration during DNA replication and to reveal how replication timing and genotoxic stress impact on final chromatin state. This highly topical project brings together the fields of chromatin biology, DNA replication, epigenetics and genome stability and we expect to make groundbreaking discoveries that will improve our understanding of human development, somatic cell reprogramming and complex diseases like cancer.
The proposed research will 1) identify and characterize novel mechanisms in chromatin restoration and 2) address molecularly how replication timing and genotoxic insults influence chromatin maturation and final chromatin state.
Max ERC Funding
1 692 737 €
Duration
Start date: 2011-11-01, End date: 2017-04-30
Project acronym CIRCUITASSEMBLY
Project Development of functional organization of the visual circuits in mice
Researcher (PI) Keisuke Yonehara
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary The key organizing principles that characterize neuronal systems include asymmetric, parallel, and topographic connectivity of the neural circuits. The main aim of my research is to elucidate the key principles underlying functional development of neural circuits by focusing on those organizing principles. I choose mouse visual system as my model since it contains all of these principles and provides sophisticated genetic tools to label and manipulate individual circuit components. My research is based on the central hypothesis that the mechanisms of brain development cannot be fully understood without first identifying individual functional cell types in adults, and then understanding how the functions of these cell types become established, using cell-type-specific molecular and synaptic mechanisms in developing animals. Recently, I have identified several transgenic mouse lines in which specific cell types in a visual center, the superior colliculus, are labeled with Cre recombinase in both developing and adult animals. Here I will take advantage of these mouse lines to ask fundamental questions about the functional development of neural circuits. First, how are distinct sensory features processed by the parallel topographic neuronal pathways, and how do they contribute to behavior? Second, what are the molecular and synaptic mechanisms that underlie developmental circuit plasticity for forming parallel topographic neuronal maps in the brain? Third, what are the molecular mechanisms that set up spatially asymmetric circuit connectivity without the need for sensory experience? I predict that my insights into the developmental mechanism of asymmetric, parallel, and topographic connectivity and circuit plasticity will be instructive when studying other brain circuits which contain similar organizing principles.
Summary
The key organizing principles that characterize neuronal systems include asymmetric, parallel, and topographic connectivity of the neural circuits. The main aim of my research is to elucidate the key principles underlying functional development of neural circuits by focusing on those organizing principles. I choose mouse visual system as my model since it contains all of these principles and provides sophisticated genetic tools to label and manipulate individual circuit components. My research is based on the central hypothesis that the mechanisms of brain development cannot be fully understood without first identifying individual functional cell types in adults, and then understanding how the functions of these cell types become established, using cell-type-specific molecular and synaptic mechanisms in developing animals. Recently, I have identified several transgenic mouse lines in which specific cell types in a visual center, the superior colliculus, are labeled with Cre recombinase in both developing and adult animals. Here I will take advantage of these mouse lines to ask fundamental questions about the functional development of neural circuits. First, how are distinct sensory features processed by the parallel topographic neuronal pathways, and how do they contribute to behavior? Second, what are the molecular and synaptic mechanisms that underlie developmental circuit plasticity for forming parallel topographic neuronal maps in the brain? Third, what are the molecular mechanisms that set up spatially asymmetric circuit connectivity without the need for sensory experience? I predict that my insights into the developmental mechanism of asymmetric, parallel, and topographic connectivity and circuit plasticity will be instructive when studying other brain circuits which contain similar organizing principles.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-04-01, End date: 2020-03-31