Project acronym BactRNA
Project Bacterial small RNAs networks unravelling novel features of transcription and translation
Researcher (PI) Maude Audrey Guillier
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), LS2, ERC-2018-COG
Summary Regulation of gene expression plays a key role in the ability of bacteria to rapidly adapt to changing environments and to colonize extremely diverse habitats. The relatively recent discovery of a plethora of small regulatory RNAs and the beginning of their characterization has unravelled new aspects of bacterial gene expression. First, the expression of many bacterial genes responds to a complex network of both transcriptional and post-transcriptional regulators. However, the properties of the resulting regulatory circuits on the dynamics of gene expression and in the bacterial adaptive response have been poorly addressed so far. In a first part of this project, we will tackle this question by characterizing the circuits that are formed between two widespread classes of bacterial regulators, the sRNAs and the two-component systems, which act at the post-transcriptional and the transcriptional level, respectively. The study of sRNAs also led to major breakthroughs regarding the basic mechanisms of gene expression. In particular, we recently showed that repressor sRNAs can target activating stem-loop structures located within the coding region of mRNAs that promote translation initiation, in striking contrast with the previously recognized inhibitory role of mRNA structures in translation. The second objective of this project is thus to draw an unprecedented map of non-canonical translation initiation events and their regulation by sRNAs.
Overall, this project will greatly improve our understanding of how bacteria can so rapidly and successfully adapt to many different environments, and in the long term, provide clues towards the development of anti-bacterial strategies.
Summary
Regulation of gene expression plays a key role in the ability of bacteria to rapidly adapt to changing environments and to colonize extremely diverse habitats. The relatively recent discovery of a plethora of small regulatory RNAs and the beginning of their characterization has unravelled new aspects of bacterial gene expression. First, the expression of many bacterial genes responds to a complex network of both transcriptional and post-transcriptional regulators. However, the properties of the resulting regulatory circuits on the dynamics of gene expression and in the bacterial adaptive response have been poorly addressed so far. In a first part of this project, we will tackle this question by characterizing the circuits that are formed between two widespread classes of bacterial regulators, the sRNAs and the two-component systems, which act at the post-transcriptional and the transcriptional level, respectively. The study of sRNAs also led to major breakthroughs regarding the basic mechanisms of gene expression. In particular, we recently showed that repressor sRNAs can target activating stem-loop structures located within the coding region of mRNAs that promote translation initiation, in striking contrast with the previously recognized inhibitory role of mRNA structures in translation. The second objective of this project is thus to draw an unprecedented map of non-canonical translation initiation events and their regulation by sRNAs.
Overall, this project will greatly improve our understanding of how bacteria can so rapidly and successfully adapt to many different environments, and in the long term, provide clues towards the development of anti-bacterial strategies.
Max ERC Funding
1 999 754 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym ECOFEED
Project Altered eco-evolutionary feedbacks in a future climate
Researcher (PI) Julien COTE
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), LS8, ERC-2018-COG
Summary Current scenarios predict an accelerated biodiversity erosion with climate change. However, uncertainties in predictions remain large because the multitude of climate change effects from genes to ecosystems and their interdependencies are still overlooked. This incomplete vision hampers the development of effective mitigation strategies to sustain biodiversity.
Climate change can directly modify the phenotype and performance of individuals through phenotypic plasticity and evolution on contemporary time scales. The microevolution of keystone species can spread throughout the whole ecological network due to changes in species interactions and further translate into an altered ecosystem functioning. Conversely, direct impacts on communities and ecosystems can have ripple effects on the phenotypic distribution and evolution of all species of ecological networks.
Climate-driven changes at individual and population levels can shape community composition and ecosystem functioning, and vice versa, altering eco-evolutionary feedbacks, namely the reciprocal interactions between ecological and evolutionary processes. Climate-driven ecological and evolutionary dynamics are yet often investigated separately. The role of eco-evolutionary feedbacks in climate change impacts on biological systems therefore hinges on little concrete empirical evidence contrasting with a profuse theoretical development.
ECOFEED will investigate climate-dependent eco-evolutionary feedbacks using a 6 year-long realistic warming experiment reproducing natural conditions and thus allowing for both evolutionary and ecological dynamics to occur under a predicted climate change scenario. Complementary laboratory experiments will quantify reciprocal impacts of climate-dependent evolutionary and ecological changes on each other. ECOFEED will provide unprecedented insights on the eco-evolutionary feedbacks in a future climate and will ultimately help refine predictions on the future of biodiversity.
Summary
Current scenarios predict an accelerated biodiversity erosion with climate change. However, uncertainties in predictions remain large because the multitude of climate change effects from genes to ecosystems and their interdependencies are still overlooked. This incomplete vision hampers the development of effective mitigation strategies to sustain biodiversity.
Climate change can directly modify the phenotype and performance of individuals through phenotypic plasticity and evolution on contemporary time scales. The microevolution of keystone species can spread throughout the whole ecological network due to changes in species interactions and further translate into an altered ecosystem functioning. Conversely, direct impacts on communities and ecosystems can have ripple effects on the phenotypic distribution and evolution of all species of ecological networks.
Climate-driven changes at individual and population levels can shape community composition and ecosystem functioning, and vice versa, altering eco-evolutionary feedbacks, namely the reciprocal interactions between ecological and evolutionary processes. Climate-driven ecological and evolutionary dynamics are yet often investigated separately. The role of eco-evolutionary feedbacks in climate change impacts on biological systems therefore hinges on little concrete empirical evidence contrasting with a profuse theoretical development.
ECOFEED will investigate climate-dependent eco-evolutionary feedbacks using a 6 year-long realistic warming experiment reproducing natural conditions and thus allowing for both evolutionary and ecological dynamics to occur under a predicted climate change scenario. Complementary laboratory experiments will quantify reciprocal impacts of climate-dependent evolutionary and ecological changes on each other. ECOFEED will provide unprecedented insights on the eco-evolutionary feedbacks in a future climate and will ultimately help refine predictions on the future of biodiversity.
Max ERC Funding
1 983 565 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym EpiScope
Project Epigenomics and chromosome architecture one cell at a time
Researcher (PI) Marcelo NOLLMANN MARTINEZ
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), LS2, ERC-2016-COG
Summary In Eukaryotes, cellular identity and tissue-specific functions are linked to the epigenetic landscape and the multi-scale architecture of the genome. The packing of DNA into nucleosomes at the ~100 bp scale and the organization of whole chromosomes into functional territories within the nucleus are well documented. At an intermediate scale, chromosomes are organised in megabase to sub-megabase structures called Topologically Associating Domains (TADs). Critically, TADs are highly correlated to patterns of epigenetic marks determining the transcriptional state of the genes they encompass. Until now, the lack of efficient technologies to map chromosome architecture and epigenetic marks at the single-cell level have limited our understanding of the molecular actors and mechanisms implicated in the establishment and maintenance of the multi-scale architecture of chromosomes and epigenetic states, and the interplay between this architecture and other nuclear functions such as transcription.
The overall aim of EpiScope is to unveil the functional, multi-scale, 3D architecture of chromatin at the single-cell level while preserving cellular context, with a toolbox of groundbreaking high-performance microscopies (Hi-M). Hi-M will use unique combinations of multi-focus and single-molecule localization microscopies with novel DNA labeling methods and microfluidics. Hi-M will enable the study of structure-function relationships within TADs of different chromatin types and correlate single-cell variations in epigenomic patterns to 3D conformations with genomic specificity and at the nanoscale. Finally, Hi-M will be used to develop a novel high-throughput, high-content method to unveil the full pairwise distance distribution between thousands of genomic loci at the single cell level and at multiple length-scales. Our findings and technologies will shed new light into the mechanisms responsible for cellular memory, identity and differentiation.
Summary
In Eukaryotes, cellular identity and tissue-specific functions are linked to the epigenetic landscape and the multi-scale architecture of the genome. The packing of DNA into nucleosomes at the ~100 bp scale and the organization of whole chromosomes into functional territories within the nucleus are well documented. At an intermediate scale, chromosomes are organised in megabase to sub-megabase structures called Topologically Associating Domains (TADs). Critically, TADs are highly correlated to patterns of epigenetic marks determining the transcriptional state of the genes they encompass. Until now, the lack of efficient technologies to map chromosome architecture and epigenetic marks at the single-cell level have limited our understanding of the molecular actors and mechanisms implicated in the establishment and maintenance of the multi-scale architecture of chromosomes and epigenetic states, and the interplay between this architecture and other nuclear functions such as transcription.
The overall aim of EpiScope is to unveil the functional, multi-scale, 3D architecture of chromatin at the single-cell level while preserving cellular context, with a toolbox of groundbreaking high-performance microscopies (Hi-M). Hi-M will use unique combinations of multi-focus and single-molecule localization microscopies with novel DNA labeling methods and microfluidics. Hi-M will enable the study of structure-function relationships within TADs of different chromatin types and correlate single-cell variations in epigenomic patterns to 3D conformations with genomic specificity and at the nanoscale. Finally, Hi-M will be used to develop a novel high-throughput, high-content method to unveil the full pairwise distance distribution between thousands of genomic loci at the single cell level and at multiple length-scales. Our findings and technologies will shed new light into the mechanisms responsible for cellular memory, identity and differentiation.
Max ERC Funding
1 999 780 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym FRAGCLIM
Project The Combined Effects of Climatic Warming and Habitat Fragmentation on Biodiversity, Community Dynamics and Ecosystem Functioning
Researcher (PI) Jose Maria MONTOYA TERAN
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), LS8, ERC-2016-COG
Summary Climatic warming and habitat fragmentation are the largest threats to biodiversity and ecosystems globally. To forecast and mitigate their effects is the environmental challenge of our age. Despite substantial progress on the ecological consequences of climatic warming and habitat fragmentation individually, there is a fundamental gap in our understanding and prediction of their combined effects.
The goal of FRAGCLIM is to determine the individual and combined effects of climatic warming and habitat fragmentation on biodiversity, community dynamics, and ecosystem functioning in complex multitrophic communities. To achieve this, it uses an integrative approach that combines the development of new theory on metacommunities and temperature-dependent food web dynamics in close dialogue with a unique long-term aquatic mesocosm experiment. It is articulated around five objectives. In the first three, FRAGCLIM will determine the effects of (i) warming, (ii) fragmentation, and (iii) warming and fragmentation combined, on numerous facets of biodiversity, community structure, food web dynamics, spatial and temporal stability, and key ecosystem functions. Then, it will (iv) investigate the extent of evolutionary thermal adaptation to warming and isolation due to fragmentation, and its consequences for biodiversity dynamics. Finally, (v) it will provide creative solutions to mitigate the combined effects of warming and fragmentation.
FRAGCLIM proposes an ambitious integrative and innovative research programme that will provide a much-needed new perspective on the ecological and evolutionary consequences of warming and fragmentation. It will greatly contribute to bridging the gaps between theoretical and empirical ecology, and between ecological and evolutionary responses to global change. FRAGCLIM will foster links with environmental policy by providing new mitigation measures to climate change in fragmented systems that derive from our theoretical and empirical findings.
Summary
Climatic warming and habitat fragmentation are the largest threats to biodiversity and ecosystems globally. To forecast and mitigate their effects is the environmental challenge of our age. Despite substantial progress on the ecological consequences of climatic warming and habitat fragmentation individually, there is a fundamental gap in our understanding and prediction of their combined effects.
The goal of FRAGCLIM is to determine the individual and combined effects of climatic warming and habitat fragmentation on biodiversity, community dynamics, and ecosystem functioning in complex multitrophic communities. To achieve this, it uses an integrative approach that combines the development of new theory on metacommunities and temperature-dependent food web dynamics in close dialogue with a unique long-term aquatic mesocosm experiment. It is articulated around five objectives. In the first three, FRAGCLIM will determine the effects of (i) warming, (ii) fragmentation, and (iii) warming and fragmentation combined, on numerous facets of biodiversity, community structure, food web dynamics, spatial and temporal stability, and key ecosystem functions. Then, it will (iv) investigate the extent of evolutionary thermal adaptation to warming and isolation due to fragmentation, and its consequences for biodiversity dynamics. Finally, (v) it will provide creative solutions to mitigate the combined effects of warming and fragmentation.
FRAGCLIM proposes an ambitious integrative and innovative research programme that will provide a much-needed new perspective on the ecological and evolutionary consequences of warming and fragmentation. It will greatly contribute to bridging the gaps between theoretical and empirical ecology, and between ecological and evolutionary responses to global change. FRAGCLIM will foster links with environmental policy by providing new mitigation measures to climate change in fragmented systems that derive from our theoretical and empirical findings.
Max ERC Funding
1 998 802 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym METACHROM
Project Establishment and maintenance of gene expression by heterochromatin factors
Researcher (PI) Jerome DEJARDIN
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Consolidator Grant (CoG), LS2, ERC-2016-COG
Summary Metastable epialleles are alleles that are variably expressed in genetically identical individuals. These epialleles are established during early development by epigenetic modifications in a process influenced by stress and the environment. The epiallele’s state can subsequently be maintained throughout development and adult life. Studying the mechanisms underlying establishment and maintenance of chromatin states is critical to understanding how the environment can shape the epigenome and how it can impact on diseases and aging. Most mouse metastable epialleles result from a nearby insertion of an endogenous retrovirus, which induces position effect variegation. In mouse embryonic stem cells, these elements are silenced by the histone methyl-transferase SETDB1 which imparts heterochromatin features by tri-methylating histone H3 on lysine 9. In the same cells, telomeric H3K9me3 is also installed by SETDB1 but surprisingly, we found that H3K9me3 correlates with enhanced transcriptional activity at telomeres. I hypothesize here that metastable chromatin states are controlled by H3K9me3 and associated factors, which are targeted to defined positions that can either instruct silencing, or support active expression. To understand how metastable chromatin states are regulated, we will first use a locus-specific chromatin proteomics approach to identify H3K9me3-dependent factors in the contexts of transcription or repression. Next, both pathways will be reconstituted by tethering those factors at specific positions on model genes, and maintenance of these states will be analyzed. Finally, to obtain a comprehensive picture of the metastable states establishment and maintenance, we will map heterochromatin factors genome-wide, in response to distinct stimuli in mESCs. This proposal will deepen our understanding of the mechanisms by which mammals use gene regulation to adapt to environmental conditions.
Summary
Metastable epialleles are alleles that are variably expressed in genetically identical individuals. These epialleles are established during early development by epigenetic modifications in a process influenced by stress and the environment. The epiallele’s state can subsequently be maintained throughout development and adult life. Studying the mechanisms underlying establishment and maintenance of chromatin states is critical to understanding how the environment can shape the epigenome and how it can impact on diseases and aging. Most mouse metastable epialleles result from a nearby insertion of an endogenous retrovirus, which induces position effect variegation. In mouse embryonic stem cells, these elements are silenced by the histone methyl-transferase SETDB1 which imparts heterochromatin features by tri-methylating histone H3 on lysine 9. In the same cells, telomeric H3K9me3 is also installed by SETDB1 but surprisingly, we found that H3K9me3 correlates with enhanced transcriptional activity at telomeres. I hypothesize here that metastable chromatin states are controlled by H3K9me3 and associated factors, which are targeted to defined positions that can either instruct silencing, or support active expression. To understand how metastable chromatin states are regulated, we will first use a locus-specific chromatin proteomics approach to identify H3K9me3-dependent factors in the contexts of transcription or repression. Next, both pathways will be reconstituted by tethering those factors at specific positions on model genes, and maintenance of these states will be analyzed. Finally, to obtain a comprehensive picture of the metastable states establishment and maintenance, we will map heterochromatin factors genome-wide, in response to distinct stimuli in mESCs. This proposal will deepen our understanding of the mechanisms by which mammals use gene regulation to adapt to environmental conditions.
Max ERC Funding
1 999 025 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym RESISTANCE
Project Resistance evolution in response to spatially variable pathogen communities
Researcher (PI) Anna-Liisa LAINE
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Consolidator Grant (CoG), LS8, ERC-2016-COG
Summary Pathogens are prevalent across all ecosystems. Given the threats imposed by pathogens on their hosts, the ability to resist infection is one key determinant of an individual’s reproductive success and survival. According to theory, resistance evolution is driven by pathogen-imposed selection and constrained by host life-history trade-offs. However, resistance evolution is traditionally studied within the “one host-one pathogen” framework, although it is becoming increasingly clear that a single host individual is exploited by diverse pathogen communities. Unravelling this diversity is the key to understanding selection for resistance, and the key aim of this proposal is to bridge this gap between theory and data. The specific objectives of this proposal are to: i) Assess spatio-temporal variation in pathogen communities and their determinants through community modeling; ii) Quantify the role of host resistance in shaping its pathogen community; iii) Unravel resistance mechanisms that determine pathogen communities by combining experimental and molecular approaches; iv) Quantify immediate and cross-generational fitness consequences that different pathogen communities inflict on their host, and v) Validate the experimental results by assessing how past disease communities have shaped host resistance in natural populations. This ambitious goal is now attainable for the first time because over the past decade my research group has amassed long-term data on hundreds of Plantago lanceolata populations in the Åland Islands, and an extensive genetic sample and seed collection that allow estimating past disease communities and resistance evolution through time. Jointly the objectives of this proposal will provide an unprecedented synthesis of how resistance functions and evolves under realistic pathogen loads, with far reaching implications for both redefining the conceptual framework for resistance evolution and for tackling real-world health and food security problems.
Summary
Pathogens are prevalent across all ecosystems. Given the threats imposed by pathogens on their hosts, the ability to resist infection is one key determinant of an individual’s reproductive success and survival. According to theory, resistance evolution is driven by pathogen-imposed selection and constrained by host life-history trade-offs. However, resistance evolution is traditionally studied within the “one host-one pathogen” framework, although it is becoming increasingly clear that a single host individual is exploited by diverse pathogen communities. Unravelling this diversity is the key to understanding selection for resistance, and the key aim of this proposal is to bridge this gap between theory and data. The specific objectives of this proposal are to: i) Assess spatio-temporal variation in pathogen communities and their determinants through community modeling; ii) Quantify the role of host resistance in shaping its pathogen community; iii) Unravel resistance mechanisms that determine pathogen communities by combining experimental and molecular approaches; iv) Quantify immediate and cross-generational fitness consequences that different pathogen communities inflict on their host, and v) Validate the experimental results by assessing how past disease communities have shaped host resistance in natural populations. This ambitious goal is now attainable for the first time because over the past decade my research group has amassed long-term data on hundreds of Plantago lanceolata populations in the Åland Islands, and an extensive genetic sample and seed collection that allow estimating past disease communities and resistance evolution through time. Jointly the objectives of this proposal will provide an unprecedented synthesis of how resistance functions and evolves under realistic pathogen loads, with far reaching implications for both redefining the conceptual framework for resistance evolution and for tackling real-world health and food security problems.
Max ERC Funding
1 999 995 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
