Project acronym 3DEpi
Project Transgenerational epigenetic inheritance of chromatin states : the role of Polycomb and 3D chromosome architecture
Researcher (PI) Giacomo CAVALLI
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), LS2, ERC-2017-ADG
Summary Epigenetic inheritance entails transmission of phenotypic traits not encoded in the DNA sequence and, in the most extreme case, Transgenerational Epigenetic Inheritance (TEI) involves transmission of memory through multiple generations. Very little is known on the mechanisms governing TEI and this is the subject of the present proposal. By transiently enhancing long-range chromatin interactions, we recently established isogenic Drosophila epilines that carry stable alternative epialleles, defined by differential levels of the Polycomb-dependent H3K27me3 mark. Furthermore, we extended our paradigm to natural phenotypes. These are ideal systems to study the role of Polycomb group (PcG) proteins and other components in regulating nuclear organization and epigenetic inheritance of chromatin states. The present project conjugates genetics, epigenomics, imaging and molecular biology to reach three critical aims.
Aim 1: Analysis of the molecular mechanisms regulating Polycomb-mediated TEI. We will identify the DNA, protein and RNA components that trigger and maintain transgenerational chromatin inheritance as well as their mechanisms of action.
Aim 2: Role of 3D genome organization in the regulation of TEI. We will analyze the developmental dynamics of TEI-inducing long-range chromatin interactions, identify chromatin components mediating 3D chromatin contacts and characterize their function in the TEI process.
Aim 3: Identification of a broader role of TEI during development. TEI might reflect a normal role of PcG components in the transmission of parental chromatin onto the next embryonic generation. We will explore this possibility by establishing other TEI paradigms and by relating TEI to the normal PcG function in these systems and in normal development.
This research program will unravel the biological significance and the molecular underpinnings of TEI and lead the way towards establishing this area of research into a consolidated scientific discipline.
Summary
Epigenetic inheritance entails transmission of phenotypic traits not encoded in the DNA sequence and, in the most extreme case, Transgenerational Epigenetic Inheritance (TEI) involves transmission of memory through multiple generations. Very little is known on the mechanisms governing TEI and this is the subject of the present proposal. By transiently enhancing long-range chromatin interactions, we recently established isogenic Drosophila epilines that carry stable alternative epialleles, defined by differential levels of the Polycomb-dependent H3K27me3 mark. Furthermore, we extended our paradigm to natural phenotypes. These are ideal systems to study the role of Polycomb group (PcG) proteins and other components in regulating nuclear organization and epigenetic inheritance of chromatin states. The present project conjugates genetics, epigenomics, imaging and molecular biology to reach three critical aims.
Aim 1: Analysis of the molecular mechanisms regulating Polycomb-mediated TEI. We will identify the DNA, protein and RNA components that trigger and maintain transgenerational chromatin inheritance as well as their mechanisms of action.
Aim 2: Role of 3D genome organization in the regulation of TEI. We will analyze the developmental dynamics of TEI-inducing long-range chromatin interactions, identify chromatin components mediating 3D chromatin contacts and characterize their function in the TEI process.
Aim 3: Identification of a broader role of TEI during development. TEI might reflect a normal role of PcG components in the transmission of parental chromatin onto the next embryonic generation. We will explore this possibility by establishing other TEI paradigms and by relating TEI to the normal PcG function in these systems and in normal development.
This research program will unravel the biological significance and the molecular underpinnings of TEI and lead the way towards establishing this area of research into a consolidated scientific discipline.
Max ERC Funding
2 500 000 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym 4D-GenEx
Project Spatio-temporal Organization and Expression of the Genome
Researcher (PI) Antoine COULON
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS2, ERC-2017-STG
Summary This project investigates the two-way relationship between spatio-temporal genome organization and coordinated gene regulation, through an approach at the interface between physics, computer science and biology.
In the nucleus, preferred positions are observed from chromosomes to single genes, in relation to normal and pathological cellular states. Evidence indicates a complex spatio-temporal coupling between co-regulated genes: e.g. certain genes cluster spatially when responding to similar factors and transcriptional noise patterns suggest domain-wide mechanisms. Yet, no individual experiment allows probing transcriptional coordination in 4 dimensions (FISH, live locus tracking, Hi-C...). Interpreting such data also critically requires theory (stochastic processes, statistical physics…). A lack of appropriate experimental/analytical approaches is impairing our understanding of the 4D genome.
Our proposal combines cutting-edge single-molecule imaging, signal-theory data analysis and physical modeling to study how genes coordinate in space and time in a single nucleus. Our objectives are to understand (a) competition/recycling of shared resources between genes within subnuclear compartments, (b) how enhancers communicate with genes domain-wide, and (c) the role of local conformational dynamics and supercoiling in gene co-regulation. Our organizing hypothesis is that, by acting on their microenvironment, genes shape their co-expression with other genes.
Building upon my expertise, we will use dual-color MS2/PP7 RNA labeling to visualize for the first time transcription and motion of pairs of hormone-responsive genes in real time. With our innovative signal analysis tools, we will extract spatio-temporal signatures of underlying processes, which we will investigate with stochastic modeling and validate through experimental perturbations. We expect to uncover how the functional organization of the linear genome relates to its physical properties and dynamics in 4D.
Summary
This project investigates the two-way relationship between spatio-temporal genome organization and coordinated gene regulation, through an approach at the interface between physics, computer science and biology.
In the nucleus, preferred positions are observed from chromosomes to single genes, in relation to normal and pathological cellular states. Evidence indicates a complex spatio-temporal coupling between co-regulated genes: e.g. certain genes cluster spatially when responding to similar factors and transcriptional noise patterns suggest domain-wide mechanisms. Yet, no individual experiment allows probing transcriptional coordination in 4 dimensions (FISH, live locus tracking, Hi-C...). Interpreting such data also critically requires theory (stochastic processes, statistical physics…). A lack of appropriate experimental/analytical approaches is impairing our understanding of the 4D genome.
Our proposal combines cutting-edge single-molecule imaging, signal-theory data analysis and physical modeling to study how genes coordinate in space and time in a single nucleus. Our objectives are to understand (a) competition/recycling of shared resources between genes within subnuclear compartments, (b) how enhancers communicate with genes domain-wide, and (c) the role of local conformational dynamics and supercoiling in gene co-regulation. Our organizing hypothesis is that, by acting on their microenvironment, genes shape their co-expression with other genes.
Building upon my expertise, we will use dual-color MS2/PP7 RNA labeling to visualize for the first time transcription and motion of pairs of hormone-responsive genes in real time. With our innovative signal analysis tools, we will extract spatio-temporal signatures of underlying processes, which we will investigate with stochastic modeling and validate through experimental perturbations. We expect to uncover how the functional organization of the linear genome relates to its physical properties and dynamics in 4D.
Max ERC Funding
1 499 750 €
Duration
Start date: 2018-04-01, End date: 2023-03-31
Project acronym ADMIRE
Project Atomic-scale Design of Majorana states and their Innovative Real-space Exploration
Researcher (PI) Roland WIESENDANGER
Host Institution (HI) UNIVERSITAET HAMBURG
Call Details Advanced Grant (AdG), PE3, ERC-2017-ADG
Summary Fault-tolerant topological quantum computation has become one of the most exciting research directions in modern condensed matter physics. As a key operation the braiding of non-Abelian anyons has been proposed theoretically. Such exotic quasiparticles can be realized as zero-energy Majorana bound states at the ends of one-dimensional magnetic nanowires in proximity to s-wave superconductors in the presence of high spin-orbit coupling. In contrast to previous attempts to realize such systems experimentally, based on the growth of semiconducting nanowires or the self-assembly of ferromagnetic nanowires on s-wave superconductors, we propose to design Majorana bound states in artificially constructed single-atom chains with non-collinear spin-textures on elemental superconducting substrates using scanning tunnelling microscope (STM)-based atom manipulation techniques. We would like to study at the atomic level the formation of Shiba bands as a result of hybridization of individual Shiba impurity states as well as the emergence of zero-energy Majorana bound states as a function of chain structure, length, and composition. Moreover, we will construct model-type platforms, such as T-junctions, rings, and more complex network structures with atomic-scale precision as a basis for demonstrating the manipulation and braiding of Majorana bound states. We will make use of sophisticated experimental techniques, such as spin-resolved scanning tunnelling spectroscopy (STS) at micro-eV energy resolution, scanning Josephson tunnelling spectroscopy, and multi-probe STS under well-defined ultra-high vacuum conditions, in order to directly probe the nature of the magnetic state of the atomic wires, the spin-polarization of the emergent Majorana states, as well as the spatial nature of the superconducting order parameter in real space. Finally, we will try to directly probe the quantum exchange statistics of non-Abelian anyons in these atomically precise fabricated model-type systems.
Summary
Fault-tolerant topological quantum computation has become one of the most exciting research directions in modern condensed matter physics. As a key operation the braiding of non-Abelian anyons has been proposed theoretically. Such exotic quasiparticles can be realized as zero-energy Majorana bound states at the ends of one-dimensional magnetic nanowires in proximity to s-wave superconductors in the presence of high spin-orbit coupling. In contrast to previous attempts to realize such systems experimentally, based on the growth of semiconducting nanowires or the self-assembly of ferromagnetic nanowires on s-wave superconductors, we propose to design Majorana bound states in artificially constructed single-atom chains with non-collinear spin-textures on elemental superconducting substrates using scanning tunnelling microscope (STM)-based atom manipulation techniques. We would like to study at the atomic level the formation of Shiba bands as a result of hybridization of individual Shiba impurity states as well as the emergence of zero-energy Majorana bound states as a function of chain structure, length, and composition. Moreover, we will construct model-type platforms, such as T-junctions, rings, and more complex network structures with atomic-scale precision as a basis for demonstrating the manipulation and braiding of Majorana bound states. We will make use of sophisticated experimental techniques, such as spin-resolved scanning tunnelling spectroscopy (STS) at micro-eV energy resolution, scanning Josephson tunnelling spectroscopy, and multi-probe STS under well-defined ultra-high vacuum conditions, in order to directly probe the nature of the magnetic state of the atomic wires, the spin-polarization of the emergent Majorana states, as well as the spatial nature of the superconducting order parameter in real space. Finally, we will try to directly probe the quantum exchange statistics of non-Abelian anyons in these atomically precise fabricated model-type systems.
Max ERC Funding
2 499 750 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym APOGEE
Project Atomic-scale physics of single-photon sources.
Researcher (PI) GUILLAUME ARTHUR FRANCOIS SCHULL
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), PE3, ERC-2017-COG
Summary Single-photon sources (SPSs) are systems capable of emitting photons one by one. These sources are of major importance for quantum-information science and applications. SPSs experiments generally rely on the optical excitation of two level systems of atomic-scale dimensions (single-molecules, vacancies in diamond…). Many fundamental questions related to the nature of these sources and the impact of their environment remain to be explored:
Can SPSs be addressed with atomic-scale spatial accuracy? How do the nanometer-scale distance or the orientation between two (or more) SPSs affect their emission properties? Does coherence emerge from the proximity between the sources? Do these structures still behave as SPSs or do they lead to the emission of correlated photons? How can we then control the degree of entanglement between the sources? Can we remotely excite the emission of these sources by using molecular chains as charge-carrying wires? Can we couple SPSs embodied in one or two-dimensional arrays? How does mechanical stress or localised plasmons affect the properties of an electrically-driven SPS?
Answering these questions requires probing, manipulating and exciting SPSs with an atomic-scale precision. This is beyond what is attainable with an all-optical method. Since they can be confined to atomic-scale pathways we propose to use electrons rather than photons to excite the SPSs. This unconventional approach provides a direct access to the atomic-scale physics of SPSs and is relevant for the implementation of these sources in hybrid devices combining electronic and photonic components. To this end, a scanning probe microscope will be developed that provides simultaneous spatial, chemical, spectral, and temporal resolutions. Single-molecules and defects in monolayer transition metal dichalcogenides are SPSs that will be studied in the project, and which are respectively of interest for fundamental and more applied issues.
Summary
Single-photon sources (SPSs) are systems capable of emitting photons one by one. These sources are of major importance for quantum-information science and applications. SPSs experiments generally rely on the optical excitation of two level systems of atomic-scale dimensions (single-molecules, vacancies in diamond…). Many fundamental questions related to the nature of these sources and the impact of their environment remain to be explored:
Can SPSs be addressed with atomic-scale spatial accuracy? How do the nanometer-scale distance or the orientation between two (or more) SPSs affect their emission properties? Does coherence emerge from the proximity between the sources? Do these structures still behave as SPSs or do they lead to the emission of correlated photons? How can we then control the degree of entanglement between the sources? Can we remotely excite the emission of these sources by using molecular chains as charge-carrying wires? Can we couple SPSs embodied in one or two-dimensional arrays? How does mechanical stress or localised plasmons affect the properties of an electrically-driven SPS?
Answering these questions requires probing, manipulating and exciting SPSs with an atomic-scale precision. This is beyond what is attainable with an all-optical method. Since they can be confined to atomic-scale pathways we propose to use electrons rather than photons to excite the SPSs. This unconventional approach provides a direct access to the atomic-scale physics of SPSs and is relevant for the implementation of these sources in hybrid devices combining electronic and photonic components. To this end, a scanning probe microscope will be developed that provides simultaneous spatial, chemical, spectral, and temporal resolutions. Single-molecules and defects in monolayer transition metal dichalcogenides are SPSs that will be studied in the project, and which are respectively of interest for fundamental and more applied issues.
Max ERC Funding
1 996 848 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym BETLIV
Project Returning to a Better Place: The (Re)assessment of the ‘Good Life’ in Times of Crisis
Researcher (PI) Valerio SIMONI RIBA
Host Institution (HI) FONDATION POUR L INSTITUT DE HAUTES ETUDES INTERNATIONALES ET DU DEVELOPPEMENT
Call Details Starting Grant (StG), SH5, ERC-2017-STG
Summary What makes for a valuable and good life is a question that many people in the contemporary world ask themselves, yet it is one that social science research has seldom addressed. Only recently have scholars started undertaking inductive comparative research on different notions of the ‘good life’, highlighting socio-cultural variations and calling for a better understanding of the different imaginaries, aspirations and values that guide people in their quest for better living conditions. Research is still lacking, however, on how people themselves evaluate, compare, and put into perspective different visions of good living and their socio-cultural anchorage. This project addresses such questions from an anthropological perspective, proposing an innovative study of how ideals of the good life are articulated, (re)assessed, and related to specific places and contexts as a result of the experience of crisis and migration. The case studies chosen to operationalize these lines of enquiry focus on the phenomenon of return migration, and consist in an analysis of the imaginaries and experience of return by Ecuadorian and Cuban men and women who migrated to Spain, are dissatisfied with their life there, and envisage/carry out the project of going back to their countries of origin (Ecuador and Cuba respectively). The project’s ambition is to bring together and contribute to three main scholarly areas of enquiry: 1) the study of morality, ethics and what counts as ‘good life’, 2) the study of the field of economic practice, its definition, value regimes, and ‘crises’, and 3) the study of migratory aspirations, projects, and trajectories. A multi-sited endeavour, the research is designed in three subprojects carried out in Spain (PhD student), Ecuador (Post-Doc), and Cuba (PI), in which ethnographic methods will be used to provide the first empirically grounded study of the links between notions and experiences of crisis, return migration, and the (re)assessment of good living.
Summary
What makes for a valuable and good life is a question that many people in the contemporary world ask themselves, yet it is one that social science research has seldom addressed. Only recently have scholars started undertaking inductive comparative research on different notions of the ‘good life’, highlighting socio-cultural variations and calling for a better understanding of the different imaginaries, aspirations and values that guide people in their quest for better living conditions. Research is still lacking, however, on how people themselves evaluate, compare, and put into perspective different visions of good living and their socio-cultural anchorage. This project addresses such questions from an anthropological perspective, proposing an innovative study of how ideals of the good life are articulated, (re)assessed, and related to specific places and contexts as a result of the experience of crisis and migration. The case studies chosen to operationalize these lines of enquiry focus on the phenomenon of return migration, and consist in an analysis of the imaginaries and experience of return by Ecuadorian and Cuban men and women who migrated to Spain, are dissatisfied with their life there, and envisage/carry out the project of going back to their countries of origin (Ecuador and Cuba respectively). The project’s ambition is to bring together and contribute to three main scholarly areas of enquiry: 1) the study of morality, ethics and what counts as ‘good life’, 2) the study of the field of economic practice, its definition, value regimes, and ‘crises’, and 3) the study of migratory aspirations, projects, and trajectories. A multi-sited endeavour, the research is designed in three subprojects carried out in Spain (PhD student), Ecuador (Post-Doc), and Cuba (PI), in which ethnographic methods will be used to provide the first empirically grounded study of the links between notions and experiences of crisis, return migration, and the (re)assessment of good living.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym BioMeTRe
Project Biophysical mechanisms of long-range transcriptional regulation
Researcher (PI) Luca GIORGETTI
Host Institution (HI) FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Call Details Starting Grant (StG), LS2, ERC-2017-STG
Summary In mammals, transcriptional control of many genes relies on cis-regulatory elements such as enhancers, which are often located tens to hundreds of kilobases away from their cognate promoters. Functional interactions between distal regulatory elements and target promoters require mutual physical proximity, which is linked to the three-dimensional structure of the chromatin fiber. Chromosome conformation capture studies revealed that chromosomes are partitioned into Topologically Associating Domains (TADs), sub-megabase domains of preferential physical interactions of the chromatin fiber. Genetic evidence showed that TAD boundaries restrict the genomic range of enhancer-promoter communication, and that interactions between regulatory sequences within TADs are further fine-tuned by smaller-scale structures. However, the mechanistic details of how physical interactions translate into transcriptional outputs are totally unknown. Here we propose to explore the biophysical mechanisms that link chromosome conformation and long-range transcriptional regulation using molecular biology, genetic engineering, single-cell experiments and physical modeling. We will measure chromosomal interactions in single cells and in time using a novel method that relies on an enzymatic process in vivo. Genetic engineering will be used to establish a cell system that allows quantitative measurement of how enhancer-promoter interactions relate to transcription at the population and single-cell levels, and to test the effects of perturbations without confounding effects. Finally, we will develop physical models of promoter operation in the presence of distal enhancers, which will be used to interpret the experimental data and formulate new testable predictions. With this integrated approach we aim at providing an entirely new layer of description of the general principles underlying transcriptional control, which could establish new paradigms for research in epigenetics and gene regulation.
Summary
In mammals, transcriptional control of many genes relies on cis-regulatory elements such as enhancers, which are often located tens to hundreds of kilobases away from their cognate promoters. Functional interactions between distal regulatory elements and target promoters require mutual physical proximity, which is linked to the three-dimensional structure of the chromatin fiber. Chromosome conformation capture studies revealed that chromosomes are partitioned into Topologically Associating Domains (TADs), sub-megabase domains of preferential physical interactions of the chromatin fiber. Genetic evidence showed that TAD boundaries restrict the genomic range of enhancer-promoter communication, and that interactions between regulatory sequences within TADs are further fine-tuned by smaller-scale structures. However, the mechanistic details of how physical interactions translate into transcriptional outputs are totally unknown. Here we propose to explore the biophysical mechanisms that link chromosome conformation and long-range transcriptional regulation using molecular biology, genetic engineering, single-cell experiments and physical modeling. We will measure chromosomal interactions in single cells and in time using a novel method that relies on an enzymatic process in vivo. Genetic engineering will be used to establish a cell system that allows quantitative measurement of how enhancer-promoter interactions relate to transcription at the population and single-cell levels, and to test the effects of perturbations without confounding effects. Finally, we will develop physical models of promoter operation in the presence of distal enhancers, which will be used to interpret the experimental data and formulate new testable predictions. With this integrated approach we aim at providing an entirely new layer of description of the general principles underlying transcriptional control, which could establish new paradigms for research in epigenetics and gene regulation.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym CASTLES
Project Charge And Spin in TopologicaL Edge States
Researcher (PI) ERWANN YANN EMILE BOCQUILLON
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE3, ERC-2017-STG
Summary Topology provides mathematical tools to sort objects according to global properties regardless of local details, and manifests itself in various fields of physics. In solid-state physics, specific topological properties of the band structure, such as a band inversion, can for example robustly enforce the appearance of spin-polarized conducting states at the boundaries of the material, while its bulk remains insulating. The boundary states of these ‘topological insulators’ in fact provide a support system to encode information non-locally in ‘topological quantum bits’ robust to local perturbations. The emerging ‘topological quantum computation’ is as such an envisioned solution to decoherence problems in the realization of quantum computers. Despite immense theoretical and experimental efforts, the rise of these new materials has however been hampered by strong difficulties to observe robust and clear signatures of their predicted properties such as spin-polarization or perfect conductance.
These challenges strongly motivate my proposal to study two-dimensional topological insulators, and in particular explore the unknown dynamics of their topological edge states in normal and superconducting regimes. First it is possible to capture information both on charge and spin dynamics, and more clearly highlight the basic properties of topological edge states. Second, the dynamics reveals the effects of Coulomb interactions, an unexplored aspect that may explain the fragility of topological edge states. Finally, it enables the manipulation and characterization of quantum states on short time scales, relevant to quantum information processing. This project relies on the powerful toolbox offered by radiofrequency and current-correlations techniques and promises to open a new field of dynamical explorations of topological materials.
Summary
Topology provides mathematical tools to sort objects according to global properties regardless of local details, and manifests itself in various fields of physics. In solid-state physics, specific topological properties of the band structure, such as a band inversion, can for example robustly enforce the appearance of spin-polarized conducting states at the boundaries of the material, while its bulk remains insulating. The boundary states of these ‘topological insulators’ in fact provide a support system to encode information non-locally in ‘topological quantum bits’ robust to local perturbations. The emerging ‘topological quantum computation’ is as such an envisioned solution to decoherence problems in the realization of quantum computers. Despite immense theoretical and experimental efforts, the rise of these new materials has however been hampered by strong difficulties to observe robust and clear signatures of their predicted properties such as spin-polarization or perfect conductance.
These challenges strongly motivate my proposal to study two-dimensional topological insulators, and in particular explore the unknown dynamics of their topological edge states in normal and superconducting regimes. First it is possible to capture information both on charge and spin dynamics, and more clearly highlight the basic properties of topological edge states. Second, the dynamics reveals the effects of Coulomb interactions, an unexplored aspect that may explain the fragility of topological edge states. Finally, it enables the manipulation and characterization of quantum states on short time scales, relevant to quantum information processing. This project relies on the powerful toolbox offered by radiofrequency and current-correlations techniques and promises to open a new field of dynamical explorations of topological materials.
Max ERC Funding
1 499 940 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym CENEVO
Project A new paradigm for centromere biology:Evolution and mechanism of CenH3-independent chromosome segregation in holocentric insects
Researcher (PI) Ines DRINNENBERG
Host Institution (HI) INSTITUT CURIE
Call Details Starting Grant (StG), LS2, ERC-2017-STG
Summary Faithful chromosome segregation in all eukaryotes relies on centromeres, the chromosomal sites that recruit kinetochore proteins and mediate spindle attachment during cell division. Fundamental to centromere function is a histone H3 variant, CenH3, that initiates kinetochore assembly on centromeric DNA. CenH3 is conserved throughout most eukaryotes; its deletion is lethal in all organisms tested. These findings established the paradigm that CenH3 is an absolute requirement for centromere function. My recent findings undermined this paradigm of CenH3 essentiality. I showed that CenH3 was lost independently in four lineages of insects. These losses are concomitant with dramatic changes in their centromeric architecture, in which each lineage independently transitioned from monocentromeres (where microtubules attach to a single chromosomal region) to holocentromeres (where microtubules attach along the entire length of the chromosome). Here, I aim to characterize this unique CenH3-deficient chromosome segregation pathway. Using proteomic and genomic approaches in lepidopteran cell lines, I will determine the mechanism of CenH3-independent kinetochore assembly that led to the establishment of their holocentric architecture. Using comparative genomic approaches, I will determine whether this kinetochore assembly pathway has recurrently evolved over the course of 400 million years of evolution and its impact on the chromosome segregation machinery.
My discovery of CenH3 loss in holocentric insects establishes a new class of centromeres. My research will reveal how CenH3 that is essential in most other eukaryotes, could have become dispensable in holocentric insects. Since the evolution of this CenH3-independent chromosome segregation pathway is associated with the independent rises of holocentric architectures, my research will also provide the first insights into the transition from a monocentromere to a holocentromere.
Summary
Faithful chromosome segregation in all eukaryotes relies on centromeres, the chromosomal sites that recruit kinetochore proteins and mediate spindle attachment during cell division. Fundamental to centromere function is a histone H3 variant, CenH3, that initiates kinetochore assembly on centromeric DNA. CenH3 is conserved throughout most eukaryotes; its deletion is lethal in all organisms tested. These findings established the paradigm that CenH3 is an absolute requirement for centromere function. My recent findings undermined this paradigm of CenH3 essentiality. I showed that CenH3 was lost independently in four lineages of insects. These losses are concomitant with dramatic changes in their centromeric architecture, in which each lineage independently transitioned from monocentromeres (where microtubules attach to a single chromosomal region) to holocentromeres (where microtubules attach along the entire length of the chromosome). Here, I aim to characterize this unique CenH3-deficient chromosome segregation pathway. Using proteomic and genomic approaches in lepidopteran cell lines, I will determine the mechanism of CenH3-independent kinetochore assembly that led to the establishment of their holocentric architecture. Using comparative genomic approaches, I will determine whether this kinetochore assembly pathway has recurrently evolved over the course of 400 million years of evolution and its impact on the chromosome segregation machinery.
My discovery of CenH3 loss in holocentric insects establishes a new class of centromeres. My research will reveal how CenH3 that is essential in most other eukaryotes, could have become dispensable in holocentric insects. Since the evolution of this CenH3-independent chromosome segregation pathway is associated with the independent rises of holocentric architectures, my research will also provide the first insights into the transition from a monocentromere to a holocentromere.
Max ERC Funding
1 497 500 €
Duration
Start date: 2018-04-01, End date: 2023-03-31
Project acronym CHROMATADS
Project Chromatin Packing and Architectural Proteins in Plants
Researcher (PI) Chang LIU
Host Institution (HI) EBERHARD KARLS UNIVERSITAET TUEBINGEN
Call Details Starting Grant (StG), LS2, ERC-2017-STG
Summary The three-dimensional organization of the genome, which strikingly correlates with gene activity, is critical for many cellular processes. The evolution of molecular techniques has allowed us to unveil chromatin structure at an unprecedented resolution. The most intriguing chromatin structures observed in animals are TADs (Topologically Associating Domains), which represent the functional and structural chromatin domains demarcating the genome. Structural proteins such as insulators proteins, on the other hand, have been shown to play crucial roles in mediating the formation of TADs. However, major structural factors relevant to chromatin structure are still waiting to be discovered in land plants. My preliminary work shows that TADs are widely distributed across the rice genome, and motif sequence analysis suggests the enrichment of plant-specific transcription factors at TAD boundaries, which jointly give rise to an exciting hypothesis that these proteins might be the long-sought-after insulators in land plants. By using various state-of-the-art molecular and computational tools, this timely project aims to fill a huge gap in plant functional genomics and substantially advance our understanding of three-dimensional chromatin structure. This project consists four major aims, which collectively will uncover the identities of plant insulator proteins and generate insights into the dynamics of structural chromatin domains during stress adaptation. Aim 1 will identify and characterize the stability and plasticity of functional chromatin domains in the rice genome during temperature stress adaptation. Aim 2 will identify insulator elements and other structural features of chromatin packing in the Marchantia polymorpha genome from a structural genomics approach. Aim 3 will establish the role of candidate proteins as plant insulators. Lastly, Aim 4 will generate functional insights into the molecular mechanism by which plant insulators shape the three-dimensional genome.
Summary
The three-dimensional organization of the genome, which strikingly correlates with gene activity, is critical for many cellular processes. The evolution of molecular techniques has allowed us to unveil chromatin structure at an unprecedented resolution. The most intriguing chromatin structures observed in animals are TADs (Topologically Associating Domains), which represent the functional and structural chromatin domains demarcating the genome. Structural proteins such as insulators proteins, on the other hand, have been shown to play crucial roles in mediating the formation of TADs. However, major structural factors relevant to chromatin structure are still waiting to be discovered in land plants. My preliminary work shows that TADs are widely distributed across the rice genome, and motif sequence analysis suggests the enrichment of plant-specific transcription factors at TAD boundaries, which jointly give rise to an exciting hypothesis that these proteins might be the long-sought-after insulators in land plants. By using various state-of-the-art molecular and computational tools, this timely project aims to fill a huge gap in plant functional genomics and substantially advance our understanding of three-dimensional chromatin structure. This project consists four major aims, which collectively will uncover the identities of plant insulator proteins and generate insights into the dynamics of structural chromatin domains during stress adaptation. Aim 1 will identify and characterize the stability and plasticity of functional chromatin domains in the rice genome during temperature stress adaptation. Aim 2 will identify insulator elements and other structural features of chromatin packing in the Marchantia polymorpha genome from a structural genomics approach. Aim 3 will establish the role of candidate proteins as plant insulators. Lastly, Aim 4 will generate functional insights into the molecular mechanism by which plant insulators shape the three-dimensional genome.
Max ERC Funding
1 498 216 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym COSMOS
Project COSMOS: Computational Shaping and Modeling of Musical Structures
Researcher (PI) Elaine Chew
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), SH5, ERC-2017-ADG
Summary Music performance is considered by many to be one of the most breath taking feats of human intelligence. That music performance is a creative act is no longer a disputed fact, but the very nature of this creative work remains illusive. Taking the view that the creative work of performance is the making and shaping of music structures, and that this creative thinking is a form of problem solving, COSMOS proposes an integrated programme of research to transform our understanding of the human experience of performed music, which is almost all music that we hear, and of the creativity of music performance, which addresses how music is made. The research themes are as follows: i) to find new ways to represent, explore, and talk about performance; ii) to harness volunteer thinking (citizen science) for music performance research by focussing on structures experienced and problem solving; iii) to create sandbox environments to experiment with making performed structures; iv) to create theoretical frameworks to discover the reasoning behind the structures perceived and made; and, v) to foster community engagement by training experts to provide feedback on structure solutions so as to increase public understanding of the creative work in music performance. Analysis of the perceived and designed structures will be based on a novel duality paradigm that turns conventional computational music structure analysis on its head to reverse engineer why a perceiver or a performer chooses a particular structure. Embedded in the approach is the use of computational thinking to optimise representations and theories to ensure accuracy, robustness, efficiency, and scalability. The PI is an established performer and a leading authority in music representation, music information research, and music perception and cognition. The project will have far reaching impact, reconfiguring expert and public views of music performance and time-varying music-like sequences such as cardiac arrhythmia.
Summary
Music performance is considered by many to be one of the most breath taking feats of human intelligence. That music performance is a creative act is no longer a disputed fact, but the very nature of this creative work remains illusive. Taking the view that the creative work of performance is the making and shaping of music structures, and that this creative thinking is a form of problem solving, COSMOS proposes an integrated programme of research to transform our understanding of the human experience of performed music, which is almost all music that we hear, and of the creativity of music performance, which addresses how music is made. The research themes are as follows: i) to find new ways to represent, explore, and talk about performance; ii) to harness volunteer thinking (citizen science) for music performance research by focussing on structures experienced and problem solving; iii) to create sandbox environments to experiment with making performed structures; iv) to create theoretical frameworks to discover the reasoning behind the structures perceived and made; and, v) to foster community engagement by training experts to provide feedback on structure solutions so as to increase public understanding of the creative work in music performance. Analysis of the perceived and designed structures will be based on a novel duality paradigm that turns conventional computational music structure analysis on its head to reverse engineer why a perceiver or a performer chooses a particular structure. Embedded in the approach is the use of computational thinking to optimise representations and theories to ensure accuracy, robustness, efficiency, and scalability. The PI is an established performer and a leading authority in music representation, music information research, and music perception and cognition. The project will have far reaching impact, reconfiguring expert and public views of music performance and time-varying music-like sequences such as cardiac arrhythmia.
Max ERC Funding
2 495 776 €
Duration
Start date: 2019-06-01, End date: 2024-05-31