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 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 MATERIALIZABLE
Project MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling
Researcher (PI) Bernd BICKEL
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Starting Grant (StG), PE6, ERC-2016-STG
Summary While access to 3D-printing technology becomes ubiquitous and provides revolutionary possibilities for fabricating complex, functional, multi-material objects with stunning properties, its potential impact is currently significantly limited due to the lack of efficient and intuitive methods for content creation. Existing tools are usually restricted to expert users, have been developed based on the capabilities of traditional manufacturing processes, and do not sufficiently take fabrication constraints into account. Scientifically, we are facing the fundamental challenge that existing simulation techniques and design approaches for predicting the physical properties of materials and objects at the resolution of modern 3D printers are too slow and do not scale with increasing object complexity. The problem is extremely challenging because real world-materials exhibit extraordinary variety and complexity.
To address these challenges, I suggest a novel computational approach that facilitates intuitive design, accurate and fast simulation techniques, and a functional representation of 3D content. I propose a multi-scale representation of functional goals and hybrid models that describes the physical behavior at a coarse scale and the relationship to the underlying material composition at the resolution of the 3D printer. My approach is to combine data-driven and physically-based modeling, providing both the required speed and accuracy through smart precomputations and tailored simulation techniques that operate on the data. A key aspect of this modeling and simulation approach is to identify domains that are sufficiently low-dimensional to be correctly sampled. Subsequently, I propose the fundamental re-thinking of the workflow, leading to solutions that allow synthesizing model instances optimized on-the-fly for a specific output device. The principal applicability will be evaluated for functional goals, such as appearance, deformation, and sensing capabilities.
Summary
While access to 3D-printing technology becomes ubiquitous and provides revolutionary possibilities for fabricating complex, functional, multi-material objects with stunning properties, its potential impact is currently significantly limited due to the lack of efficient and intuitive methods for content creation. Existing tools are usually restricted to expert users, have been developed based on the capabilities of traditional manufacturing processes, and do not sufficiently take fabrication constraints into account. Scientifically, we are facing the fundamental challenge that existing simulation techniques and design approaches for predicting the physical properties of materials and objects at the resolution of modern 3D printers are too slow and do not scale with increasing object complexity. The problem is extremely challenging because real world-materials exhibit extraordinary variety and complexity.
To address these challenges, I suggest a novel computational approach that facilitates intuitive design, accurate and fast simulation techniques, and a functional representation of 3D content. I propose a multi-scale representation of functional goals and hybrid models that describes the physical behavior at a coarse scale and the relationship to the underlying material composition at the resolution of the 3D printer. My approach is to combine data-driven and physically-based modeling, providing both the required speed and accuracy through smart precomputations and tailored simulation techniques that operate on the data. A key aspect of this modeling and simulation approach is to identify domains that are sufficiently low-dimensional to be correctly sampled. Subsequently, I propose the fundamental re-thinking of the workflow, leading to solutions that allow synthesizing model instances optimized on-the-fly for a specific output device. The principal applicability will be evaluated for functional goals, such as appearance, deformation, and sensing capabilities.
Max ERC Funding
1 497 730 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
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 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
Project acronym SMART
Project Strong Modular proof Assistance: Reasoning across Theories
Researcher (PI) Cezary Seweryn KALISZYK
Host Institution (HI) UNIVERSITAET INNSBRUCK
Call Details Starting Grant (StG), PE6, ERC-2016-STG
Summary Formal proof technology delivers an unparalleled level of certainty and security. Nevertheless, applying proof assistants to the verification of complex theories and designs is still extremely laborious. High profile certification projects, such as seL4, CompCert, and Flyspeck require tens of person-years. We recently demonstrated that this effort can be significantly reduced by combining reasoning and learning in so called hammer systems: 40% of the Flyspeck, HOL4, Isabelle/HOL, and Mizar top-level lemmas can be proved automatically.
Today's early generation of hammers consists of individual systems limited to very few proof assistants. The accessible knowledge repositories are isolated, and there is no reuse of hammer components.
It is possible to achieve a breakthrough in proof automation by developing new AI methods that combine reasoning knowledge and techniques into a smart hammer, that works over a very large part of today's formalized knowledge. The main goal of the project is to develop a strong and uniform learning-reasoning system available for multiple logical foundations. To achieve this, we will develop: (a) uniform learning methods, (b) reusable ATP encoding components for different foundational aspects, (c) integration of proof reconstruction, and (d) methods for knowledge extraction, reuse and content merging. The single proof advice system will be made available for multiple proof assistants and their vast heterogeneous libraries.
The ultimate outcome is an advice system able to automatically prove half of Coq, ACL2, and Isabelle/ZF top-level theorems. Additionally we will significantly improve success rates for HOL provers and Mizar. The combined smart advice method together with the vast accumulated knowledge will result in a novel kind of tool, which allows working mathematicians to automatically find proofs of many simple conjectures, paving the way for the widespread use of formal proof in mathematics and computer science.
Summary
Formal proof technology delivers an unparalleled level of certainty and security. Nevertheless, applying proof assistants to the verification of complex theories and designs is still extremely laborious. High profile certification projects, such as seL4, CompCert, and Flyspeck require tens of person-years. We recently demonstrated that this effort can be significantly reduced by combining reasoning and learning in so called hammer systems: 40% of the Flyspeck, HOL4, Isabelle/HOL, and Mizar top-level lemmas can be proved automatically.
Today's early generation of hammers consists of individual systems limited to very few proof assistants. The accessible knowledge repositories are isolated, and there is no reuse of hammer components.
It is possible to achieve a breakthrough in proof automation by developing new AI methods that combine reasoning knowledge and techniques into a smart hammer, that works over a very large part of today's formalized knowledge. The main goal of the project is to develop a strong and uniform learning-reasoning system available for multiple logical foundations. To achieve this, we will develop: (a) uniform learning methods, (b) reusable ATP encoding components for different foundational aspects, (c) integration of proof reconstruction, and (d) methods for knowledge extraction, reuse and content merging. The single proof advice system will be made available for multiple proof assistants and their vast heterogeneous libraries.
The ultimate outcome is an advice system able to automatically prove half of Coq, ACL2, and Isabelle/ZF top-level theorems. Additionally we will significantly improve success rates for HOL provers and Mizar. The combined smart advice method together with the vast accumulated knowledge will result in a novel kind of tool, which allows working mathematicians to automatically find proofs of many simple conjectures, paving the way for the widespread use of formal proof in mathematics and computer science.
Max ERC Funding
1 449 000 €
Duration
Start date: 2017-03-01, End date: 2022-02-28