Project acronym ArcheoDyn
Project Globular clusters as living fossils of the past of galaxies
Researcher (PI) Petrus VAN DE VEN
Host Institution (HI) UNIVERSITAT WIEN
Call Details Consolidator Grant (CoG), PE9, ERC-2016-COG
Summary Globular clusters (GCs) are enigmatic objects that hide a wealth of information. They are the living fossils of the history of their native galaxies and the record keepers of the violent events that made them change their domicile. This proposal aims to mine GCs as living fossils of galaxy evolution to address fundamental questions in astrophysics: (1) Do satellite galaxies merge as predicted by the hierarchical build-up of galaxies? (2) Which are the seeds of supermassive black holes in the centres of galaxies? (3) How did star formation originate in the earliest phases of galaxy formation? To answer these questions, novel population-dependent dynamical modelling techniques are required, whose development the PI has led over the past years. This uniquely positions him to take full advantage of the emerging wealth of chemical and kinematical data on GCs.
Following the tidal disruption of satellite galaxies, their dense GCs, and maybe even their nuclei, are left as the most visible remnants in the main galaxy. The hierarchical build-up of their new host galaxy can thus be unearthed by recovering the GCs’ orbits. However, currently it is unclear which of the GCs are accretion survivors. Actually, the existence of a central intermediate mass black hole (IMBH) or of multiple stellar populations in GCs might tell which ones are accreted. At the same time, detection of IMBHs is important as they are predicted seeds for supermassive black holes in galaxies; while the multiple stellar populations in GCs are vital witnesses to the extreme modes of star formation in the early Universe. However, for every putative dynamical IMBH detection so far there is a corresponding non-detection; also the origin of multiple stellar populations in GCs still lacks any uncontrived explanation. The synergy of novel techniques and exquisite data proposed here promises a breakthrough in this emerging field of dynamical archeology with GCs as living fossils of the past of galaxies.
Summary
Globular clusters (GCs) are enigmatic objects that hide a wealth of information. They are the living fossils of the history of their native galaxies and the record keepers of the violent events that made them change their domicile. This proposal aims to mine GCs as living fossils of galaxy evolution to address fundamental questions in astrophysics: (1) Do satellite galaxies merge as predicted by the hierarchical build-up of galaxies? (2) Which are the seeds of supermassive black holes in the centres of galaxies? (3) How did star formation originate in the earliest phases of galaxy formation? To answer these questions, novel population-dependent dynamical modelling techniques are required, whose development the PI has led over the past years. This uniquely positions him to take full advantage of the emerging wealth of chemical and kinematical data on GCs.
Following the tidal disruption of satellite galaxies, their dense GCs, and maybe even their nuclei, are left as the most visible remnants in the main galaxy. The hierarchical build-up of their new host galaxy can thus be unearthed by recovering the GCs’ orbits. However, currently it is unclear which of the GCs are accretion survivors. Actually, the existence of a central intermediate mass black hole (IMBH) or of multiple stellar populations in GCs might tell which ones are accreted. At the same time, detection of IMBHs is important as they are predicted seeds for supermassive black holes in galaxies; while the multiple stellar populations in GCs are vital witnesses to the extreme modes of star formation in the early Universe. However, for every putative dynamical IMBH detection so far there is a corresponding non-detection; also the origin of multiple stellar populations in GCs still lacks any uncontrived explanation. The synergy of novel techniques and exquisite data proposed here promises a breakthrough in this emerging field of dynamical archeology with GCs as living fossils of the past of galaxies.
Max ERC Funding
1 999 250 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym DIVIMAGE
Project Bridging spatial and temporal resolution gaps in the study of cell division
Researcher (PI) Daniel Wolfram Gerlich
Host Institution (HI) INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH
Call Details Starting Grant (StG), LS3, ERC-2011-StG_20101109
Summary Cell division underlies the growth and development of all living organisms. Following partitioning of bulk cytoplasmic contents by cleavage furrow ingression, dividing animal cells split by a distinct process termed abscission. Whereas a number of factors required for abscission have been identified in previous studies, it is not known by which mechanism they mediate fission of the intercellular bridge between the nascent sister cells. Here, we will establish correlative workflows of time-lapse imaging, super resolution fluorescence microscopy, electron tomography, and electrophysiological assays to bridge spatial and temporal resolution gaps in the study of abscission. We will further develop computational tools for image-based RNAi screening. With this, we aim to:
1) elucidate how membrane and cytoskeletal dynamics coordinately split the intercellular bridge;
2) uncover the signaling pathways controlling abscission timing.
Failure in abscission can lead to aneuploidy and cancer. Elucidating its mechanism and temporal control is therefore of general biological and medical relevance. The computational and correlative imaging methods developed in this project will further provide the research community new possibilities for mechanistic studies in intact cells.
Summary
Cell division underlies the growth and development of all living organisms. Following partitioning of bulk cytoplasmic contents by cleavage furrow ingression, dividing animal cells split by a distinct process termed abscission. Whereas a number of factors required for abscission have been identified in previous studies, it is not known by which mechanism they mediate fission of the intercellular bridge between the nascent sister cells. Here, we will establish correlative workflows of time-lapse imaging, super resolution fluorescence microscopy, electron tomography, and electrophysiological assays to bridge spatial and temporal resolution gaps in the study of abscission. We will further develop computational tools for image-based RNAi screening. With this, we aim to:
1) elucidate how membrane and cytoskeletal dynamics coordinately split the intercellular bridge;
2) uncover the signaling pathways controlling abscission timing.
Failure in abscission can lead to aneuploidy and cancer. Elucidating its mechanism and temporal control is therefore of general biological and medical relevance. The computational and correlative imaging methods developed in this project will further provide the research community new possibilities for mechanistic studies in intact cells.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-03-01, End date: 2017-02-28
Project acronym ETAP
Project Tracing Evolution of Auxin Transport and Polarity in Plants
Researcher (PI) Jiri Friml
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Advanced Grant (AdG), LS3, ERC-2016-ADG
Summary Multicellularity in plants evolved independently from other eukaryotes and presents a unique, alternative way how to deal with challenges of life. A major plant developmental module is the directional transport for the plant hormone auxin. The crucial components are PIN auxin transporters, whose polar, subcellular localization determines directionality of auxin flow through tissues. PIN-dependent auxin transport represents a unique model for studying the functional link between basic cellular processes, such as vesicle trafficking and cell polarity, and their developmental outcome at the level of the multicellular organism. Despite decades of intensive research, the classical approaches in the established models are approaching their limits and many crucial questions remain unsolved, in particular related to PIN structure, regulatory motifs and evolutionary origin
I propose to start a new direction in my research using an evolutionary perspective. This promises to overcome current limitations and provides not only (i) interesting insights into PIN evolution and diversification, but also (ii) a unique opportunity to study how evolutionary conserved cellular mechanisms of e.g. endocytic trafficking evolved specific plug-ins to make them subject to plant-specific regulations. The characterization of (iii) prokaryotic PIN origin will provide a so urgently needed (iv) entry into PIN structural studies. To achieve these goals, we will also establish novel (v) genetic and cell biological models in the ancestral lineage of the land plants that will be of a great use for any plant evolutionary studies.
The intellectual and methodological challenges of such interdisciplinary strategy combining several lower and higher plant models are obvious, but our preliminary results at several fronts promise its feasibility and success to gain deeper understanding of exciting questions on evolution and mechanisms behind the coordination and specification of developmental programs.
Summary
Multicellularity in plants evolved independently from other eukaryotes and presents a unique, alternative way how to deal with challenges of life. A major plant developmental module is the directional transport for the plant hormone auxin. The crucial components are PIN auxin transporters, whose polar, subcellular localization determines directionality of auxin flow through tissues. PIN-dependent auxin transport represents a unique model for studying the functional link between basic cellular processes, such as vesicle trafficking and cell polarity, and their developmental outcome at the level of the multicellular organism. Despite decades of intensive research, the classical approaches in the established models are approaching their limits and many crucial questions remain unsolved, in particular related to PIN structure, regulatory motifs and evolutionary origin
I propose to start a new direction in my research using an evolutionary perspective. This promises to overcome current limitations and provides not only (i) interesting insights into PIN evolution and diversification, but also (ii) a unique opportunity to study how evolutionary conserved cellular mechanisms of e.g. endocytic trafficking evolved specific plug-ins to make them subject to plant-specific regulations. The characterization of (iii) prokaryotic PIN origin will provide a so urgently needed (iv) entry into PIN structural studies. To achieve these goals, we will also establish novel (v) genetic and cell biological models in the ancestral lineage of the land plants that will be of a great use for any plant evolutionary studies.
The intellectual and methodological challenges of such interdisciplinary strategy combining several lower and higher plant models are obvious, but our preliminary results at several fronts promise its feasibility and success to gain deeper understanding of exciting questions on evolution and mechanisms behind the coordination and specification of developmental programs.
Max ERC Funding
2 410 292 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym GRADIENTSENSING
Project Cellular navigation along spatial gradients
Researcher (PI) Michael Karl Sixt
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Consolidator Grant (CoG), LS3, ERC-2016-COG
Summary Gradients of extracellular signalling molecules are a central concept in biology: for example gradients of guidance-cues such as chemokines position migrating cells in development, malignancy and immunity. Because immune cells are permanently motile, their function most critically depends on spatiotemporal orchestration by a large family of chemokines. To specify direction, concentration differences of the chemokine need to be interpreted by the migrating cell. Most mechanistic knowledge about eukaryotic gradient sensing is inferred from the amoeba Dictyostelium discoideum migrating towards soluble gradients of cyclicAMP. The biology of chemokines is much more diverse, e.g. gradients can take different shapes and, importantly, they do not only emerge in the soluble but also in the immobilized phase. In this proposal we suggest to address the principles of leukocyte chemotaxis using convergent system wide, cell biological and intravital approaches. Employing a newly developed, genetically tractable primary leukocyte system, we will test the contribution of spatial and temporal signalling paradigms of gradient sensing. Quantitative microscopy will be used to image cellular responses to engineered immobilized and soluble chemokine gradients of defined shape as well as to optogenetically triggered signals. In a complementary approach we will screen for proteins responding to chemokine signalling and perform the first genome wide genome editing-based loss of function screen for directionally persistent chemotaxis and haptotaxis. Findings will be validated in vivo to guarantee physiological relevance. In a support project we will precision-engineer the genome of primary leukocytes suitable for assaying migration. A unique combination of cellular, genetic, engineering and quantitative microscopy tools will allow this new and holistic approach to a question which is not only fundamental for immunology but also for understanding development and cancer biology.
Summary
Gradients of extracellular signalling molecules are a central concept in biology: for example gradients of guidance-cues such as chemokines position migrating cells in development, malignancy and immunity. Because immune cells are permanently motile, their function most critically depends on spatiotemporal orchestration by a large family of chemokines. To specify direction, concentration differences of the chemokine need to be interpreted by the migrating cell. Most mechanistic knowledge about eukaryotic gradient sensing is inferred from the amoeba Dictyostelium discoideum migrating towards soluble gradients of cyclicAMP. The biology of chemokines is much more diverse, e.g. gradients can take different shapes and, importantly, they do not only emerge in the soluble but also in the immobilized phase. In this proposal we suggest to address the principles of leukocyte chemotaxis using convergent system wide, cell biological and intravital approaches. Employing a newly developed, genetically tractable primary leukocyte system, we will test the contribution of spatial and temporal signalling paradigms of gradient sensing. Quantitative microscopy will be used to image cellular responses to engineered immobilized and soluble chemokine gradients of defined shape as well as to optogenetically triggered signals. In a complementary approach we will screen for proteins responding to chemokine signalling and perform the first genome wide genome editing-based loss of function screen for directionally persistent chemotaxis and haptotaxis. Findings will be validated in vivo to guarantee physiological relevance. In a support project we will precision-engineer the genome of primary leukocytes suitable for assaying migration. A unique combination of cellular, genetic, engineering and quantitative microscopy tools will allow this new and holistic approach to a question which is not only fundamental for immunology but also for understanding development and cancer biology.
Max ERC Funding
1 984 922 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym LeukocyteForces
Project Cytoskeletal force generation and force transduction of migrating leukocytes
Researcher (PI) Michael Sixt
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Starting Grant (StG), LS3, ERC-2011-StG_20101109
Summary Cell migration is a universal feature of all metazoan life and crucially involved in most developmental, homeostatic and pathological processes. Most efforts to understand its molecular and mechanical aspects were focused on the “haptokinetic” paradigm. Here cells generate traction by coupling the protrusive and contractile forces of the actomyosin cytoskeleton via transmembrane receptors to the extracellular environment. Our recent work demonstrated that leukocytes, the class of animal cells that migrates with highest speed and efficiency, violate this paradigm. Once embedded in physiological three-dimensional matrices they instantaneously shift between adhesive and non-adhesive modes to transduce force. This proposal suggests a combined cell biological and biophysical approach to elucidate the molecular and mechanical principles underlying such plasticity. We will focus on the machinery most proximate to force generation and use genetics and pharmacology to characterize how nucleation, elongation, depolymerization and crosslinking of actin filaments act in leukocytes migrating through environments of varying geometry and adhesive properties (Postdoc 1). Mechanical manipulations in conjunction with high resolution monitoring of substrate deformations will reveal how cytoskeletal force is transduced to the extracellular environment (Postdoc 2). In a technical support project (Technician) we will develop a cell-system with optimized access to stable genetic manipulations. Technically, these questions will be addressed by employing advanced live cell fluorescence imaging in combination with artificial environments engineered using microfluidics and substrate micropatterning. Importantly, findings will ultimately be challenged in living tissues. This multidisciplinary approach will generate an integrated view of locomotion-plasticity that will not only impact basic cell biology and immunology but also developmental and cancer biology.
Summary
Cell migration is a universal feature of all metazoan life and crucially involved in most developmental, homeostatic and pathological processes. Most efforts to understand its molecular and mechanical aspects were focused on the “haptokinetic” paradigm. Here cells generate traction by coupling the protrusive and contractile forces of the actomyosin cytoskeleton via transmembrane receptors to the extracellular environment. Our recent work demonstrated that leukocytes, the class of animal cells that migrates with highest speed and efficiency, violate this paradigm. Once embedded in physiological three-dimensional matrices they instantaneously shift between adhesive and non-adhesive modes to transduce force. This proposal suggests a combined cell biological and biophysical approach to elucidate the molecular and mechanical principles underlying such plasticity. We will focus on the machinery most proximate to force generation and use genetics and pharmacology to characterize how nucleation, elongation, depolymerization and crosslinking of actin filaments act in leukocytes migrating through environments of varying geometry and adhesive properties (Postdoc 1). Mechanical manipulations in conjunction with high resolution monitoring of substrate deformations will reveal how cytoskeletal force is transduced to the extracellular environment (Postdoc 2). In a technical support project (Technician) we will develop a cell-system with optimized access to stable genetic manipulations. Technically, these questions will be addressed by employing advanced live cell fluorescence imaging in combination with artificial environments engineered using microfluidics and substrate micropatterning. Importantly, findings will ultimately be challenged in living tissues. This multidisciplinary approach will generate an integrated view of locomotion-plasticity that will not only impact basic cell biology and immunology but also developmental and cancer biology.
Max ERC Funding
1 458 125 €
Duration
Start date: 2012-04-01, End date: 2017-03-31
Project acronym MECSPEC
Project Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation
Researcher (PI) Carl-Philipp Joachim Werner Heisenberg
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Advanced Grant (AdG), LS3, ERC-2016-ADG
Summary Embryogenesis is achieved by the close interplay between the gene regulatory networks that control cell fate specification and the physical processes by which the embryo takes shape. While each of these systems has been extensively investigated over the past decades, comparably little is yet known about how they functionally interact across different scales of organization within the physiological context of the developing embryo. The central aim of this proposal is to elucidate the fundamental principles underlying the interaction and feedback between cell mechanics and fate specification during vertebrate gastrulation. Using zebrafish as a vertebrate model organism, we will explore how germ layer progenitor cell fate specification affects the physical processes by which the gastrula takes shape, and, vice versa, how alterations in cell/tissue mechanics feed back onto the gene regulatory networks and signals controlling progenitor cell fate specification during gastrulation. To dissect the fundamental mechanisms underlying this crosstalk, we will combine genetic, cell biological and biophysical experimentation with mathematical modeling. We expect that this transdisciplinary approach will provide answers to a central yet unresolved question in developmental biology: how the interplay between cell mechanics, dynamics and fate specification drives embryo morphogenesis and patterning.
Summary
Embryogenesis is achieved by the close interplay between the gene regulatory networks that control cell fate specification and the physical processes by which the embryo takes shape. While each of these systems has been extensively investigated over the past decades, comparably little is yet known about how they functionally interact across different scales of organization within the physiological context of the developing embryo. The central aim of this proposal is to elucidate the fundamental principles underlying the interaction and feedback between cell mechanics and fate specification during vertebrate gastrulation. Using zebrafish as a vertebrate model organism, we will explore how germ layer progenitor cell fate specification affects the physical processes by which the gastrula takes shape, and, vice versa, how alterations in cell/tissue mechanics feed back onto the gene regulatory networks and signals controlling progenitor cell fate specification during gastrulation. To dissect the fundamental mechanisms underlying this crosstalk, we will combine genetic, cell biological and biophysical experimentation with mathematical modeling. We expect that this transdisciplinary approach will provide answers to a central yet unresolved question in developmental biology: how the interplay between cell mechanics, dynamics and fate specification drives embryo morphogenesis and patterning.
Max ERC Funding
2 306 862 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym PSDP
Project POLARITY AND SUBCELLULAR DYNAMICS IN PLANTS
Researcher (PI) Jirí Friml
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Starting Grant (StG), LS3, ERC-2011-StG_20101109
Summary Plant life strategy is marked by acquisition of highly flexible development that adapts plants’ phenotype to the environment. Various environmental signals are integrated into the endogenous signalling networks involving the versatile phytohormone auxin. The intercellular auxin transport mediates a large variety of adaptive plant growth responses. Subcellular polar distribution of PIN auxin transporters determines directionality of auxin flow and thus have potential to integrate internal and external signals via the redirection of auxin fluxes and translate them into modulation of development. Auxin transport thus represents a unique model for studying the functional link between basic cellular processes, such as vesicle trafficking and cell polarity, and their developmental outcome at the level of the multicellular organism.
We will employ approaches of cell biology, molecular genetics and chemical genomics in Arabidopsis thaliana to identify the cellular and molecular mechanisms regulating the directional throughput of auxin flow a integration of environmental signals into subcellular dynamics of PIN auxin transporters as well as endogenous feed-back regulations of this mechanism.
In our proposal, we will focus on four main research directions.
1. Novel regulators of cell polarity identified by chemical genomics
2. Cellular mechanisms of cell polarity maintenance
3. Integration of signals into subcellular dynamics of auxin transport
4. Mathematical modelling of regulatory circuits for adaptive development
The results will demonstrate the viability of genetics approaches for addressing cell biological questions in plants, open new horizons in plant cell biology and plant hormone fields and inspire researchers also in non-plant fields. The expected output has clear application potential for targeted modulation of plant development. The project will further strengthen our position of world-leading laboratory in plant hormone and plant cell biology fields.
Summary
Plant life strategy is marked by acquisition of highly flexible development that adapts plants’ phenotype to the environment. Various environmental signals are integrated into the endogenous signalling networks involving the versatile phytohormone auxin. The intercellular auxin transport mediates a large variety of adaptive plant growth responses. Subcellular polar distribution of PIN auxin transporters determines directionality of auxin flow and thus have potential to integrate internal and external signals via the redirection of auxin fluxes and translate them into modulation of development. Auxin transport thus represents a unique model for studying the functional link between basic cellular processes, such as vesicle trafficking and cell polarity, and their developmental outcome at the level of the multicellular organism.
We will employ approaches of cell biology, molecular genetics and chemical genomics in Arabidopsis thaliana to identify the cellular and molecular mechanisms regulating the directional throughput of auxin flow a integration of environmental signals into subcellular dynamics of PIN auxin transporters as well as endogenous feed-back regulations of this mechanism.
In our proposal, we will focus on four main research directions.
1. Novel regulators of cell polarity identified by chemical genomics
2. Cellular mechanisms of cell polarity maintenance
3. Integration of signals into subcellular dynamics of auxin transport
4. Mathematical modelling of regulatory circuits for adaptive development
The results will demonstrate the viability of genetics approaches for addressing cell biological questions in plants, open new horizons in plant cell biology and plant hormone fields and inspire researchers also in non-plant fields. The expected output has clear application potential for targeted modulation of plant development. The project will further strengthen our position of world-leading laboratory in plant hormone and plant cell biology fields.
Max ERC Funding
1 500 000 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym REGENERATEACROSS
Project A Cross Species Approach to Understand the Mechanism and Evolution of Limb Regeneration Capacity
Researcher (PI) Elly Margaret Tanaka
Host Institution (HI) FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
Call Details Advanced Grant (AdG), LS3, ERC-2011-ADG_20110310
Summary Limb regeneration capacity varies among vertebrates, ranging from full regeneration in salamanders, to stage-restricted premetamorphic regeneration in frogs, to finger-tip regeneration in newborn mice and humans.
The molecular and cellular basis for these differences in regeneration ability is not known and it is still unclear if these different regenerative events are tied by some common mechanisms with progressive restriction due to extracellular signals or cell intrinsic changes.
Connective tissue fibroblasts or their progenitors play a key role in regenerating the patterned salamander limb. They harbor critical positional information and can reconstitute not only the connective tissue but also a complete, patterned skeleton. In contrast, such cells typically contribute to scar tissue during mammalian wound healing. Their role in mouse finger tip regeneration is unknown.
I seek to determine the differences in fibroblast biology that account for the differences in regeneration between salamander, frog and mouse. To define the differences in composition of the connective tissue population, I will perform parallel lineage tracing of different fibroblast populations and their progenitors during wound healing and regeneration in salamander, frog and mouse. To determine differences in cell intrinsic potential versus extracellular cues required for regeneration I will perform cross-species transplantation of lineage-labeled cells between salamander and frog coupled with expression profiling to identify molecular changes that occur in cells in a regenerative versus non-regenerative context. Finally I will use this expression profiling and our molecular knowledge of limb regeneration factors to test whether frog and mouse cells can acquire regenerative traits at the cellular level by the forced exposure to intracellular and extracellular regeneration cues or by the downregulation of putative inhibitory factors.
Summary
Limb regeneration capacity varies among vertebrates, ranging from full regeneration in salamanders, to stage-restricted premetamorphic regeneration in frogs, to finger-tip regeneration in newborn mice and humans.
The molecular and cellular basis for these differences in regeneration ability is not known and it is still unclear if these different regenerative events are tied by some common mechanisms with progressive restriction due to extracellular signals or cell intrinsic changes.
Connective tissue fibroblasts or their progenitors play a key role in regenerating the patterned salamander limb. They harbor critical positional information and can reconstitute not only the connective tissue but also a complete, patterned skeleton. In contrast, such cells typically contribute to scar tissue during mammalian wound healing. Their role in mouse finger tip regeneration is unknown.
I seek to determine the differences in fibroblast biology that account for the differences in regeneration between salamander, frog and mouse. To define the differences in composition of the connective tissue population, I will perform parallel lineage tracing of different fibroblast populations and their progenitors during wound healing and regeneration in salamander, frog and mouse. To determine differences in cell intrinsic potential versus extracellular cues required for regeneration I will perform cross-species transplantation of lineage-labeled cells between salamander and frog coupled with expression profiling to identify molecular changes that occur in cells in a regenerative versus non-regenerative context. Finally I will use this expression profiling and our molecular knowledge of limb regeneration factors to test whether frog and mouse cells can acquire regenerative traits at the cellular level by the forced exposure to intracellular and extracellular regeneration cues or by the downregulation of putative inhibitory factors.
Max ERC Funding
2 447 600 €
Duration
Start date: 2012-06-01, End date: 2017-12-31
Project acronym RegGeneMems
Project Understanding the evolution of regeneration-permissive gene expression and positional memory in Axolotl limb regeneration
Researcher (PI) Elly TANAKA
Host Institution (HI) FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
Call Details Advanced Grant (AdG), LS3, ERC-2016-ADG
Summary Molecular studies of development in diverse animal models have revealed the remarkably conserved set of morphogens governing growth and patterning of body axes and organ fields. Equally astounding is the diversity of form and function arising from the implementation of these morphogens. The systematic analysis of well-defined traits in closely related species has revealed how changes in gene regulatory sequences and their trans-acting factors have yielded diversity. An important future challenge is to understand, at the genome level, the evolution of animal form in situations where such a rich set of closely related species may not be available.
Vertebrate limb regeneration is a particularly fascinating yet challenging context to pursue the evolution of traits related to controlling the body plan. Amputation of the Axolotl limb results in the formation of a limb blastema that morphologically and molecularly resembles the embryonic limb bud. In this system, the limb morphogen network must be reactivated only upon tissue removal and not wounding, but also corresponding to a positional memory existing in the adult tissue. These signalling cassettes must also be deployed in a way that can scale to the size of a blastema that is vast when compared to an embryonic limb bud. An important question is whether and how the limb development network has diverged to accomodate these unique traits.
During Axolotl limb development and regeneration, some key limb morphogens display divergent expression patterns compared to other vertebrates. I hypothesize that this divergent expression has functional importance for allowing limb regeneration. My goal is to 1) understand how this divergent expression arose 2) functionally test its role in regeneration specificity and scaling, and 3) use the system to dissect the molecular nature of positional memory that is critical for regeneration. I refer to this work as “evo-reg”.
Summary
Molecular studies of development in diverse animal models have revealed the remarkably conserved set of morphogens governing growth and patterning of body axes and organ fields. Equally astounding is the diversity of form and function arising from the implementation of these morphogens. The systematic analysis of well-defined traits in closely related species has revealed how changes in gene regulatory sequences and their trans-acting factors have yielded diversity. An important future challenge is to understand, at the genome level, the evolution of animal form in situations where such a rich set of closely related species may not be available.
Vertebrate limb regeneration is a particularly fascinating yet challenging context to pursue the evolution of traits related to controlling the body plan. Amputation of the Axolotl limb results in the formation of a limb blastema that morphologically and molecularly resembles the embryonic limb bud. In this system, the limb morphogen network must be reactivated only upon tissue removal and not wounding, but also corresponding to a positional memory existing in the adult tissue. These signalling cassettes must also be deployed in a way that can scale to the size of a blastema that is vast when compared to an embryonic limb bud. An important question is whether and how the limb development network has diverged to accomodate these unique traits.
During Axolotl limb development and regeneration, some key limb morphogens display divergent expression patterns compared to other vertebrates. I hypothesize that this divergent expression has functional importance for allowing limb regeneration. My goal is to 1) understand how this divergent expression arose 2) functionally test its role in regeneration specificity and scaling, and 3) use the system to dissect the molecular nature of positional memory that is critical for regeneration. I refer to this work as “evo-reg”.
Max ERC Funding
2 325 659 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
