Project acronym ARBODYNAMIC
Project Coupling dynamic population immunity profiles and host behaviours to arboviral spread
Researcher (PI) Henrik SALJE
Host Institution (HI) INSTITUT PASTEUR
Call Details Starting Grant (StG), LS8, ERC-2018-STG
Summary Arboviruses infect millions of people each year, however, mechanisms that drive viral emergence and maintenance remain largely unknown. A combination of host factors (e.g., human mobility), mosquito factors (e.g., abundance) and viral factors (e.g., transmissibility) interconnect to drive spread. Further, for endemic arboviruses, complex patterns of population immunity, built up over many years, appear key to the emergence of particular lineages. To disentangle the contribution of these different drivers, we need detailed data from the same pathogen system over a long time period from the same location. In addition, we need new methods, which can integrate these different data sources and allow appropriate mechanistic inferences.
In this project, I will use the most globally prevalent arbovirus, dengue virus, as a case study. I will focus on Thailand where all four dengue serotypes have circulated endemically for decades and excellent long-term data and isolates exist, to address two fundamental questions:
i) How do population-level patterns of immunity evolve over time and what is their impact on strain dynamics? I will use mechanistic models applied to historic serotype-specific case data to reconstruct the evolving immune profile of the population and explore the impact of immunity on viral diversity using sequences from archived isolates from each year over a 50-year period.
ii) How do human behaviors, vector densities interact with immunity to dictate spread? I will work with geolocated full genome sequences from across Thailand and use detailed data on how people move, their contact patterns, their immunity profiles and mosquito distributions to study competing hypotheses of how arboviruses spread. I will compare the key drivers of dengue spread with that found for outbreaks of Zika and chikungunya.
This proposal addresses fundamental questions about the mechanisms that drive arboviral emergence and spread that will be relevant across disease systems.
Summary
Arboviruses infect millions of people each year, however, mechanisms that drive viral emergence and maintenance remain largely unknown. A combination of host factors (e.g., human mobility), mosquito factors (e.g., abundance) and viral factors (e.g., transmissibility) interconnect to drive spread. Further, for endemic arboviruses, complex patterns of population immunity, built up over many years, appear key to the emergence of particular lineages. To disentangle the contribution of these different drivers, we need detailed data from the same pathogen system over a long time period from the same location. In addition, we need new methods, which can integrate these different data sources and allow appropriate mechanistic inferences.
In this project, I will use the most globally prevalent arbovirus, dengue virus, as a case study. I will focus on Thailand where all four dengue serotypes have circulated endemically for decades and excellent long-term data and isolates exist, to address two fundamental questions:
i) How do population-level patterns of immunity evolve over time and what is their impact on strain dynamics? I will use mechanistic models applied to historic serotype-specific case data to reconstruct the evolving immune profile of the population and explore the impact of immunity on viral diversity using sequences from archived isolates from each year over a 50-year period.
ii) How do human behaviors, vector densities interact with immunity to dictate spread? I will work with geolocated full genome sequences from across Thailand and use detailed data on how people move, their contact patterns, their immunity profiles and mosquito distributions to study competing hypotheses of how arboviruses spread. I will compare the key drivers of dengue spread with that found for outbreaks of Zika and chikungunya.
This proposal addresses fundamental questions about the mechanisms that drive arboviral emergence and spread that will be relevant across disease systems.
Max ERC Funding
1 499 896 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym EMERG-ANT
Project Ant navigation: how complex behaviours emerge from mini-brains in interaction with their natural habitats
Researcher (PI) Antoine WYSTRACH
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS8, ERC-2017-STG
Summary Navigation is one of the most crucial and most challenging problems animals face. Behavioural analyses have shown that animals make use of a number of different mechanisms to navigate, but very little is known of how spatial information is processed and integrated by the brain. This project will exploit the stunning ability of ants in learning long visual routes to investigate the mechanisms of navigation in a brain numerically much simpler than vertebrate. We will combine an ecological approach with state-of-the-art technologies to enable a thorough control of sensory-motor cues while the ant is navigating in virtual-reality reconstructions of its natural environments. This new and powerful method will enable us to dissect the mechanisms underlying the emergence of navigational behaviours by performing straightforward manipulations. The results will be modelled in the light of insect neurobiology and integrated into an increasingly complete neural architecture. This neural architecture will be embedded into an agent navigating in the same virtual-reality environment as the real ants for testing. The advantage of such an inter-disciplinary approach is that failures of our agent will help us identify gaps in our knowledge and thus fuel new experimentation. Reciprocally, our agent will become increasingly refined in the light of incoming experimental results. This will create a positive feedback towards a complete, multi-level understanding of navigation in the wild. The findings will inspire new robust solutions for navigational problems that can be applied to bio-robotics.
Summary
Navigation is one of the most crucial and most challenging problems animals face. Behavioural analyses have shown that animals make use of a number of different mechanisms to navigate, but very little is known of how spatial information is processed and integrated by the brain. This project will exploit the stunning ability of ants in learning long visual routes to investigate the mechanisms of navigation in a brain numerically much simpler than vertebrate. We will combine an ecological approach with state-of-the-art technologies to enable a thorough control of sensory-motor cues while the ant is navigating in virtual-reality reconstructions of its natural environments. This new and powerful method will enable us to dissect the mechanisms underlying the emergence of navigational behaviours by performing straightforward manipulations. The results will be modelled in the light of insect neurobiology and integrated into an increasingly complete neural architecture. This neural architecture will be embedded into an agent navigating in the same virtual-reality environment as the real ants for testing. The advantage of such an inter-disciplinary approach is that failures of our agent will help us identify gaps in our knowledge and thus fuel new experimentation. Reciprocally, our agent will become increasingly refined in the light of incoming experimental results. This will create a positive feedback towards a complete, multi-level understanding of navigation in the wild. The findings will inspire new robust solutions for navigational problems that can be applied to bio-robotics.
Max ERC Funding
1 439 893 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym ENDOSEXDET
Project The impact of endosymbionts on the evolution of host sex determination mechanisms
Researcher (PI) Richard Cordaux
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS8, ERC-2010-StG_20091118
Summary Appreciation of endosymbiosis, a type of symbiosis in which a microbial partner lives within its host cells, as an important source of evolutionary novelty has developed relatively recently. In this proposal, we investigate a fundamental evolutionary process influenced by bacterial endosymbionts: the mechanisms of sex determination of their eukaryotic hosts.
In animals, the most common system of sex determination is genetic. It can also be affected by inherited bacterial endosymbionts. However, very few systems have been analyzed and there is no extensive empirical evidence of how endosymbionts can shape host sex-determining systems. In the isopod crustacean Armadillidium vulgare, genetic sex determination follows female heterogamety. However, many A. vulgare populations harbour Wolbachia bacterial endosymbionts which can invert genetic males into phenotypic functional females.
Other sex-determining factors have been identified in A. vulgare: a feminizing f element which may be a Wolbachia genome fragment carrying feminization information inserted into the host nuclear genome, and a masculinizing gene which can restore the male sex in the presence of the f element, as a result of a genetic conflict. Thus, sex determination mechanisms in A. vulgare seem to be largely driven by Wolbachia endosymbionts. However, the molecular genetic basis and evolutionary history of all these sex-determining factors is unknown.
The A. vulgare/Wolbachia model provides a unique opportunity for directly investigating the impact of endosymbionts on the evolution of host sex determination mechanisms at the molecular genetic level. We will address this issue using the latest developments of molecular genetics technologies, such as next-generation DNA sequencing and high throughput genotyping.
Summary
Appreciation of endosymbiosis, a type of symbiosis in which a microbial partner lives within its host cells, as an important source of evolutionary novelty has developed relatively recently. In this proposal, we investigate a fundamental evolutionary process influenced by bacterial endosymbionts: the mechanisms of sex determination of their eukaryotic hosts.
In animals, the most common system of sex determination is genetic. It can also be affected by inherited bacterial endosymbionts. However, very few systems have been analyzed and there is no extensive empirical evidence of how endosymbionts can shape host sex-determining systems. In the isopod crustacean Armadillidium vulgare, genetic sex determination follows female heterogamety. However, many A. vulgare populations harbour Wolbachia bacterial endosymbionts which can invert genetic males into phenotypic functional females.
Other sex-determining factors have been identified in A. vulgare: a feminizing f element which may be a Wolbachia genome fragment carrying feminization information inserted into the host nuclear genome, and a masculinizing gene which can restore the male sex in the presence of the f element, as a result of a genetic conflict. Thus, sex determination mechanisms in A. vulgare seem to be largely driven by Wolbachia endosymbionts. However, the molecular genetic basis and evolutionary history of all these sex-determining factors is unknown.
The A. vulgare/Wolbachia model provides a unique opportunity for directly investigating the impact of endosymbionts on the evolution of host sex determination mechanisms at the molecular genetic level. We will address this issue using the latest developments of molecular genetics technologies, such as next-generation DNA sequencing and high throughput genotyping.
Max ERC Funding
1 403 285 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym EVOLEPID
Project Evolutionary Epidemiology of Infectious Diseases
Researcher (PI) Sylvain Michel Marie Gandon
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS8, ERC-2009-StG
Summary Our ability to control infectious diseases relies on a better understanding of epidemiological and evolutionary dynamics of pathogens. I will develop a research program combining theoretical and experimental approaches. First, I will extend the theoretical framework of evolutionary epidemiology into several new directions to study (1) the evolution of host and pathogen key life-history traits (parasite virulence, host resistance and host manipulation by the parasite) and, (2) the dynamics of adaptation of pathogens in constant and variable environments. This part of the project will be grounded on both mathematical epidemiology and population genetics. Second, I will use two biological models to test some of these theoretical predictions both in the laboratory and in the field: (1) I will study the interaction between the avian malaria parasite (Plasmodium relictum) and its mosquito vector (Culex pipiens) to test some of the predictions generated on life-history evolution, and in particular on host manipulation by the parasite. (2) I will study the evolutionary dynamics of the coliphage phix174 under different scenarios of environmental heterogeneity to test the predictions issued from models on the dynamics of adaptation in variable environments. In addition, I will measure patterns of adaptation across space and time using natural samples of viral and bacterial communities. The originality of this project lays in the combination of different perspectives on the dynamics of infectious diseases, ranging from theoretical population genetics to experimental behavioural ecology and evolution. Combining these different perspectives will yield a more comprehensive view of the dynamics of infectious diseases and contribute to the improvement of public-health interventions.
Summary
Our ability to control infectious diseases relies on a better understanding of epidemiological and evolutionary dynamics of pathogens. I will develop a research program combining theoretical and experimental approaches. First, I will extend the theoretical framework of evolutionary epidemiology into several new directions to study (1) the evolution of host and pathogen key life-history traits (parasite virulence, host resistance and host manipulation by the parasite) and, (2) the dynamics of adaptation of pathogens in constant and variable environments. This part of the project will be grounded on both mathematical epidemiology and population genetics. Second, I will use two biological models to test some of these theoretical predictions both in the laboratory and in the field: (1) I will study the interaction between the avian malaria parasite (Plasmodium relictum) and its mosquito vector (Culex pipiens) to test some of the predictions generated on life-history evolution, and in particular on host manipulation by the parasite. (2) I will study the evolutionary dynamics of the coliphage phix174 under different scenarios of environmental heterogeneity to test the predictions issued from models on the dynamics of adaptation in variable environments. In addition, I will measure patterns of adaptation across space and time using natural samples of viral and bacterial communities. The originality of this project lays in the combination of different perspectives on the dynamics of infectious diseases, ranging from theoretical population genetics to experimental behavioural ecology and evolution. Combining these different perspectives will yield a more comprehensive view of the dynamics of infectious diseases and contribute to the improvement of public-health interventions.
Max ERC Funding
1 308 660 €
Duration
Start date: 2010-01-01, End date: 2014-12-31
Project acronym EVOMOBILOME
Project Evolution of gene mobility: how mobile elements shape the function and sociality of microbial communities
Researcher (PI) Eduardo Pimentel Cachapuz Rocha
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS8, ERC-2011-StG_20101109
Summary Prokaryotes evolve rapidly new functionalities by horizontal gene transfer delivered by mobile genetic elements (MGE). MGE increase relatedness between individuals and thereby might also promote the establishment of microbial social networks. Many studies have detailed the dynamics of specific systems in specific MGE. Yet, how MGE key and accessory functions evolve as a whole at the face of social dilemmas arising in microbial communities is largely ignored. Here, I aim at an integrative identification and analysis of self-mobilizable elements to unravel an evolutionary framework of MGE contributions to prokaryotic evolution.
We will use sequence similarity, phylogeny and population genetics techniques to detail how elements propagate and are maintained in populations. We will investigate how accessory functions work together in relation to interactions between MGE and of MGE with the host. We will then quantify the long-term impact of MGE to the gene repertoires of prokaryotes by analysis of the patterns of their degradation and/or domestication using regulatory networks and population genetics. The analysis of secretion systems and effectors in mobile elements will enlighten the role of gene mobility in promoting social behaviours thorugh production of public goods. The previous results will then be used to query metagenomics datasets about the roles of gene mobility and secretion in the social evolution of natural microbial populations.
This work will pioneer the application of theoretical works in population genetics and social evolution to the study of natural microbial communities by way of evolutionary genomics. Its integrative outlook will also provide essential breakthroughs in the understanding of the evolutionary history of mechanisms of gene mobility, e.g. conjugation. Finally, this project will pinpoint how manipulation of MGE might allows control of virulence, antibiotic resistance and other phenomena related with microbial social interactions.
Summary
Prokaryotes evolve rapidly new functionalities by horizontal gene transfer delivered by mobile genetic elements (MGE). MGE increase relatedness between individuals and thereby might also promote the establishment of microbial social networks. Many studies have detailed the dynamics of specific systems in specific MGE. Yet, how MGE key and accessory functions evolve as a whole at the face of social dilemmas arising in microbial communities is largely ignored. Here, I aim at an integrative identification and analysis of self-mobilizable elements to unravel an evolutionary framework of MGE contributions to prokaryotic evolution.
We will use sequence similarity, phylogeny and population genetics techniques to detail how elements propagate and are maintained in populations. We will investigate how accessory functions work together in relation to interactions between MGE and of MGE with the host. We will then quantify the long-term impact of MGE to the gene repertoires of prokaryotes by analysis of the patterns of their degradation and/or domestication using regulatory networks and population genetics. The analysis of secretion systems and effectors in mobile elements will enlighten the role of gene mobility in promoting social behaviours thorugh production of public goods. The previous results will then be used to query metagenomics datasets about the roles of gene mobility and secretion in the social evolution of natural microbial populations.
This work will pioneer the application of theoretical works in population genetics and social evolution to the study of natural microbial communities by way of evolutionary genomics. Its integrative outlook will also provide essential breakthroughs in the understanding of the evolutionary history of mechanisms of gene mobility, e.g. conjugation. Finally, this project will pinpoint how manipulation of MGE might allows control of virulence, antibiotic resistance and other phenomena related with microbial social interactions.
Max ERC Funding
1 298 925 €
Duration
Start date: 2012-07-01, End date: 2017-12-31
Project acronym EXPTEVOLCELEGANS
Project A study on the interaction among natural selection, mutation and recombination, with Caenorhabditis elegans experimental evolution
Researcher (PI) Henrique Nuno Patricio Carreira Pereira Teotonio
Host Institution (HI) ECOLE NORMALE SUPERIEURE
Call Details Starting Grant (StG), LS8, ERC-2009-StG
Summary The process of adaptation to novel environments is of extraordinary importance to understand the existence of biological diversity. The development of a theory of adaptation during the last 150 years identified natural selection as its cause, and the conditions under which it depends on the existence of the heritable variation encoded in DNA sequences, introduced in finite populations by mutation, recombination and migration. Despite the considerable knowledge about the mechanism of evolution, an understanding of genetic basis of adaptation remains both a theoretical and an empirical challenge. In this project we propose to conduct an unprecedented large scale evolution experiment with the androdioecious nematode Caenorhabditis elegans, under varying levels of outcrossing rates, initial standing genetic variation and frequency of environmental change. With the integration of information from several levels of structural organization, from fitness-proxy and life-history phenotypes to genome wide RNA expression, it will be possible to determine the several genetic and environmental components of diversity. Furthermore, we will perform whole genome linkage disequilibrium (LD) association mapping with experimental evolution, thus determining at the DNA sequence level how the genome is organized and how it feeds back into the population genetic dynamics. Tests of evolutionary theory will be conducted with the data collected. Directional natural selection is expected to maintain genotype diversity, when there are non-linear interactions among several loci. But predominantly stabilizing selection will erode this genetic diversity. While in the first scenario outcrossing will be favoured, in the second it will be a hindrance to adaptation. After an initial characterization, we will work with ~90 populations and measure >104 phenotypes. For mapping we will assay an estimated 106 genotypes. Most of the analytical tools have already been developed.
Summary
The process of adaptation to novel environments is of extraordinary importance to understand the existence of biological diversity. The development of a theory of adaptation during the last 150 years identified natural selection as its cause, and the conditions under which it depends on the existence of the heritable variation encoded in DNA sequences, introduced in finite populations by mutation, recombination and migration. Despite the considerable knowledge about the mechanism of evolution, an understanding of genetic basis of adaptation remains both a theoretical and an empirical challenge. In this project we propose to conduct an unprecedented large scale evolution experiment with the androdioecious nematode Caenorhabditis elegans, under varying levels of outcrossing rates, initial standing genetic variation and frequency of environmental change. With the integration of information from several levels of structural organization, from fitness-proxy and life-history phenotypes to genome wide RNA expression, it will be possible to determine the several genetic and environmental components of diversity. Furthermore, we will perform whole genome linkage disequilibrium (LD) association mapping with experimental evolution, thus determining at the DNA sequence level how the genome is organized and how it feeds back into the population genetic dynamics. Tests of evolutionary theory will be conducted with the data collected. Directional natural selection is expected to maintain genotype diversity, when there are non-linear interactions among several loci. But predominantly stabilizing selection will erode this genetic diversity. While in the first scenario outcrossing will be favoured, in the second it will be a hindrance to adaptation. After an initial characterization, we will work with ~90 populations and measure >104 phenotypes. For mapping we will assay an estimated 106 genotypes. Most of the analytical tools have already been developed.
Max ERC Funding
1 694 000 €
Duration
Start date: 2010-02-01, End date: 2016-01-31
Project acronym FluctEvol
Project Fluctuating selection, evolution, and plasticity in random environments
Researcher (PI) Luis-Miguel Chevin
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS8, ERC-2015-STG
Summary Temporal environmental variation in natural systems includes a large component of random fluctuations, the magnitude and predictability of which is modified under current climate change. The need for predicting eco-evolutionary impacts of plastic and evolutionary responses to changing environments is still hampered by lack of strong experimental evidence. FluctEvol aims at shedding a new light on population responses to stochastic environments, and facilitating their prediction, using a unique combination of approaches. First, theoretical models of evolution and demography under a randomly changing optimum phenotype will be designed and analysed, producing new quantitative predictions. Second, statistical methodologies will be developed, and employed in meta-analyses of long-term datasets from natural populations. And third, large-scale and automated experimental evolution in stochastic environments will be carried out with the micro-alga Dunaliella salina, an extremophile that thrives at high and variable salinities. We will manipulate the magnitude and predictability of fluctuations in salinity, and use high-throughput phenotyping and candidate-gene sequencing to analyse the evolution of plasticity for traits involved in salinity adaptation in this species: glycerol and carotene content. We will thus combine the benefits of experimental evolution in microbes (short generations, ample replication) with a priori knowledge of ecologically relevant adaptive traits, allowing for hypothesis-driven experiments. The success of this project in increasing our predictive power about eco-evolutionary dynamics is warranted by the experience of the PI, at the interface between theoretical and empirical approaches. Our experiments will have relevance beyond academia, as we will modify through evolution the plasticity of traits (accumulation of energetic cell metabolites) that are direct targets for bioindustry, thus potentially overcoming current limitations in productivity.
Summary
Temporal environmental variation in natural systems includes a large component of random fluctuations, the magnitude and predictability of which is modified under current climate change. The need for predicting eco-evolutionary impacts of plastic and evolutionary responses to changing environments is still hampered by lack of strong experimental evidence. FluctEvol aims at shedding a new light on population responses to stochastic environments, and facilitating their prediction, using a unique combination of approaches. First, theoretical models of evolution and demography under a randomly changing optimum phenotype will be designed and analysed, producing new quantitative predictions. Second, statistical methodologies will be developed, and employed in meta-analyses of long-term datasets from natural populations. And third, large-scale and automated experimental evolution in stochastic environments will be carried out with the micro-alga Dunaliella salina, an extremophile that thrives at high and variable salinities. We will manipulate the magnitude and predictability of fluctuations in salinity, and use high-throughput phenotyping and candidate-gene sequencing to analyse the evolution of plasticity for traits involved in salinity adaptation in this species: glycerol and carotene content. We will thus combine the benefits of experimental evolution in microbes (short generations, ample replication) with a priori knowledge of ecologically relevant adaptive traits, allowing for hypothesis-driven experiments. The success of this project in increasing our predictive power about eco-evolutionary dynamics is warranted by the experience of the PI, at the interface between theoretical and empirical approaches. Our experiments will have relevance beyond academia, as we will modify through evolution the plasticity of traits (accumulation of energetic cell metabolites) that are direct targets for bioindustry, thus potentially overcoming current limitations in productivity.
Max ERC Funding
1 499 665 €
Duration
Start date: 2016-03-01, End date: 2021-02-28
Project acronym GENOMEFUN
Project Genomics of adaptive divergence in Fungi
Researcher (PI) Tatiana Giraud
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary Understanding the genetic and genomic processes behind adaptive phenotypes remains a holy grail in biology. Fungi are poorly studied regarding these processes, despite their great tractability as model eukaryote organisms and their medical, industrial, and ecological importance. This project therefore aims to investigate the major evolutionary forces in the adaptive divergence of fungi —as model eukaryotes with small genomes— by the integration of high-throughput sequencing and innovative approaches. Two groups of fungi will be used to investigate different time scales and footprints of adaptation. The first model group are Penicillium fungal species. Some species being used for cheese and antibiotic production, they are excellent models for understanding adaptive processes under strong and recent selection. The second model is Microbotryum violaceum, a complex of sibling species, causing anther smut disease on different Caryophyllaceae plant species. This model is ideal to address the question of long term pathogen-host adaptation. We will integrate high-throughput sequencing and state-of-the-art inference methods to identify the evolutionary processes involved in adaptive divergence and the genomic consequences of domestication. Different experimental and sequencing approaches will then help to validate the flagged genes and genomic regions. The proposed research should yield unprecedented insights into the genomics of adaptive divergence, i.e. on the kinds of traits, the genetic architecture of these traits, the genomic regions and processes involved, and the importance of neutral processes. There are also applied implications for understanding emerging fungal diseases in plants and processes of domestication in micro-organisms, and more generally adaptation to global changes.
Summary
Understanding the genetic and genomic processes behind adaptive phenotypes remains a holy grail in biology. Fungi are poorly studied regarding these processes, despite their great tractability as model eukaryote organisms and their medical, industrial, and ecological importance. This project therefore aims to investigate the major evolutionary forces in the adaptive divergence of fungi —as model eukaryotes with small genomes— by the integration of high-throughput sequencing and innovative approaches. Two groups of fungi will be used to investigate different time scales and footprints of adaptation. The first model group are Penicillium fungal species. Some species being used for cheese and antibiotic production, they are excellent models for understanding adaptive processes under strong and recent selection. The second model is Microbotryum violaceum, a complex of sibling species, causing anther smut disease on different Caryophyllaceae plant species. This model is ideal to address the question of long term pathogen-host adaptation. We will integrate high-throughput sequencing and state-of-the-art inference methods to identify the evolutionary processes involved in adaptive divergence and the genomic consequences of domestication. Different experimental and sequencing approaches will then help to validate the flagged genes and genomic regions. The proposed research should yield unprecedented insights into the genomics of adaptive divergence, i.e. on the kinds of traits, the genetic architecture of these traits, the genomic regions and processes involved, and the importance of neutral processes. There are also applied implications for understanding emerging fungal diseases in plants and processes of domestication in micro-organisms, and more generally adaptation to global changes.
Max ERC Funding
1 498 741 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym GENPHENBACT
Project Genetic and Phenotypic Modelling of Bacterial Evolution
Researcher (PI) Olivier Antoine Tenaillon
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary "The dramatic success of infectious agents comes from their ability to adapt to both immune and pharmaceutical selective pressures. To uncover the dynamics of bacterial adaptation, experimental evolution has been widely used, focusing mostly on organismal fitness. Many of the observation derived from these experiments have been captured by Fisher's Geometric model of Adaptation (FGMA). Despite its success, this top-down phenotypic model is relatively abstract. In fact, its most important parameter, the number of independent phenotypes an organism expose to the action of natural selection, or phenotypic complexity, remains completely disconnected from a genetic perspective. More recently, bottom-up genotype to phenotype maps from system biology have provided an alternative to unravel the constraints regulating bacterial evolution.
In the present project, I want to connect these different approaches. The interpretation of system biology models in terms of FGMA will (i) uncover the genetic determinants of phenotypic complexity, giving more genetic context to FGMA, and, (ii) transpose our understanding of evolution through FGMA to complex genotype to phenotype maps.
Four different levels of integration will be used: the gene, the metabolic network, the organism and the species. I will use
-antibiotic resistance gene, TEM1, to connect thermodynamic models of protein evolution to FGMA, and characterize the phenotypic complexity of a single gene,
-computational models of metabolic network and experimental modification of a biochemical pathway regulation to assess the meaning of phenotypic complexity in networks,
-in vitro and in vivo experimental evolution coupled with genome sequencing and mutant reconstruction to assess the molecular bases of changes in beneficial mutation rates during organismal adaptation,
- faeces of well characterised human twins to assess the factors of the human gut's environment that shape the genetic diversity of the Escherichia coli species."
Summary
"The dramatic success of infectious agents comes from their ability to adapt to both immune and pharmaceutical selective pressures. To uncover the dynamics of bacterial adaptation, experimental evolution has been widely used, focusing mostly on organismal fitness. Many of the observation derived from these experiments have been captured by Fisher's Geometric model of Adaptation (FGMA). Despite its success, this top-down phenotypic model is relatively abstract. In fact, its most important parameter, the number of independent phenotypes an organism expose to the action of natural selection, or phenotypic complexity, remains completely disconnected from a genetic perspective. More recently, bottom-up genotype to phenotype maps from system biology have provided an alternative to unravel the constraints regulating bacterial evolution.
In the present project, I want to connect these different approaches. The interpretation of system biology models in terms of FGMA will (i) uncover the genetic determinants of phenotypic complexity, giving more genetic context to FGMA, and, (ii) transpose our understanding of evolution through FGMA to complex genotype to phenotype maps.
Four different levels of integration will be used: the gene, the metabolic network, the organism and the species. I will use
-antibiotic resistance gene, TEM1, to connect thermodynamic models of protein evolution to FGMA, and characterize the phenotypic complexity of a single gene,
-computational models of metabolic network and experimental modification of a biochemical pathway regulation to assess the meaning of phenotypic complexity in networks,
-in vitro and in vivo experimental evolution coupled with genome sequencing and mutant reconstruction to assess the molecular bases of changes in beneficial mutation rates during organismal adaptation,
- faeces of well characterised human twins to assess the factors of the human gut's environment that shape the genetic diversity of the Escherichia coli species."
Max ERC Funding
1 485 600 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym GRAVIBONE
Project How Bone Adapts to Heavy Weight?Bone Morphological and Microanatomical Adaptation to the Mechanical Constraints Imposed by Graviportality
Researcher (PI) Alexandra Christine HOUSSAYE
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS8, ERC-2016-STG
Summary Heavy animals, said to be graviportal, are under strong mechanical constraints. Their skeleton, notably their limb bones, show convergent morpho-functional adaptations that surprisingly remain very poorly studied. Understanding the convergent and specific adaptations of bone to weight bearing in taxa with various morphologies, sizes, habitats and locomotor behaviours is essential to understand how bone responds to biomechanical constraints. In palaeontology, it will allow determining how giant fossil animals could move and support their weight. The study of graviportality provides an ideal case-study to analyse form-function relationship in a macro-evolutionary context.
GRAVIBONE proposes a broad and modern comparative investigation of the biomechanical adaptations of the outer and inner bone anatomy of long bones observable in different modern and fossil taxa that have converged on graviportality. It combines various approaches using recently developed powerful methods and tools (notably the innovative integration of the whole 3D external and internal bone anatomy in biomechanical modelling) and uses these in an explicit phylogenetic context. Characterizing the various adaptive traits observed in extant taxa and understanding the link between specific isolated microanatomical, morphological and mechanical parameters will enable to: a) define degrees/types of adaptations to graviportality, b) make palaeoecological and paleofunctional inferences, and c) explain adaptations to graviportality in amniote evolutionary history. This new and highly integrative approach will increase our knowledge on the adaptation of the vertebrate skeleton and thereby of the organisms, to environmental demands.
Summary
Heavy animals, said to be graviportal, are under strong mechanical constraints. Their skeleton, notably their limb bones, show convergent morpho-functional adaptations that surprisingly remain very poorly studied. Understanding the convergent and specific adaptations of bone to weight bearing in taxa with various morphologies, sizes, habitats and locomotor behaviours is essential to understand how bone responds to biomechanical constraints. In palaeontology, it will allow determining how giant fossil animals could move and support their weight. The study of graviportality provides an ideal case-study to analyse form-function relationship in a macro-evolutionary context.
GRAVIBONE proposes a broad and modern comparative investigation of the biomechanical adaptations of the outer and inner bone anatomy of long bones observable in different modern and fossil taxa that have converged on graviportality. It combines various approaches using recently developed powerful methods and tools (notably the innovative integration of the whole 3D external and internal bone anatomy in biomechanical modelling) and uses these in an explicit phylogenetic context. Characterizing the various adaptive traits observed in extant taxa and understanding the link between specific isolated microanatomical, morphological and mechanical parameters will enable to: a) define degrees/types of adaptations to graviportality, b) make palaeoecological and paleofunctional inferences, and c) explain adaptations to graviportality in amniote evolutionary history. This new and highly integrative approach will increase our knowledge on the adaptation of the vertebrate skeleton and thereby of the organisms, to environmental demands.
Max ERC Funding
1 082 450 €
Duration
Start date: 2017-04-01, End date: 2022-03-31