Project acronym ALPHA
Project Alpha Shape Theory Extended
Researcher (PI) Herbert Edelsbrunner
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Call Details Advanced Grant (AdG), PE6, ERC-2017-ADG
Summary Alpha shapes were invented in the early 80s of last century, and their implementation in three dimensions in the early 90s was at the forefront of the exact arithmetic paradigm that enabled fast and correct geometric software. In the late 90s, alpha shapes motivated the development of the wrap algorithm for surface reconstruction, and of persistent homology, which was the starting point of rapidly expanding interest in topological algorithms aimed at data analysis questions.
We now see alpha shapes, wrap complexes, and persistent homology as three aspects of a larger theory, which we propose to fully develop. This viewpoint was a long time coming and finds its clear expression within a generalized
version of discrete Morse theory. This unified framework offers new opportunities, including
(I) the adaptive reconstruction of shapes driven by the cavity structure;
(II) the stochastic analysis of all aspects of the theory;
(III) the computation of persistence of dense data, both in scale and in depth;
(IV) the study of long-range order in periodic and near-periodic point configurations.
These capabilities will significantly deepen as well as widen the theory and enable new applications in the sciences. To gain focus, we concentrate on low-dimensional applications in structural molecular biology and particle systems.
Summary
Alpha shapes were invented in the early 80s of last century, and their implementation in three dimensions in the early 90s was at the forefront of the exact arithmetic paradigm that enabled fast and correct geometric software. In the late 90s, alpha shapes motivated the development of the wrap algorithm for surface reconstruction, and of persistent homology, which was the starting point of rapidly expanding interest in topological algorithms aimed at data analysis questions.
We now see alpha shapes, wrap complexes, and persistent homology as three aspects of a larger theory, which we propose to fully develop. This viewpoint was a long time coming and finds its clear expression within a generalized
version of discrete Morse theory. This unified framework offers new opportunities, including
(I) the adaptive reconstruction of shapes driven by the cavity structure;
(II) the stochastic analysis of all aspects of the theory;
(III) the computation of persistence of dense data, both in scale and in depth;
(IV) the study of long-range order in periodic and near-periodic point configurations.
These capabilities will significantly deepen as well as widen the theory and enable new applications in the sciences. To gain focus, we concentrate on low-dimensional applications in structural molecular biology and particle systems.
Max ERC Funding
1 678 432 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
Project acronym AMBH
Project Ancient Music Beyond Hellenisation
Researcher (PI) Stefan HAGEL
Host Institution (HI) OESTERREICHISCHE AKADEMIE DER WISSENSCHAFTEN
Call Details Advanced Grant (AdG), SH5, ERC-2017-ADG
Summary From medieval times, Arabic as well as European music was analysed in terms that were inherited from Classical Antiquity and had thus developed in a very different music culture. In spite of recent breakthroughs in the understanding of the latter, whose technicalities we access not only through texts and iconography, but also through instrument finds and surviving notated melodies, its relation to music traditions known from later periods and different places is almost uncharted territory.
The present project explores relations between Hellenic/Hellenistic music as pervaded the theatres and concert halls throughout and beyond the Roman empire, Near Eastern traditions – from the diatonic system emerging from cuneiform sources to the flourishing musical world of the caliphates – and, as far as possible, African musical life south of Egypt as well – a region that maintained close ties both with the Hellenised culture of its northern neighbours and with the Arabian Peninsula.
On the one hand, this demands collaboration between Classical Philology and Arabic Studies, extending methods recently developed within music archaeological research related to the Classical Mediterranean. Arabic writings need to be examined in close reading, using recent insights into the interplay between ancient music theory and practice, in order to segregate the influence of Greek thinking from ideas and facts that must relate to contemporaneous ‘Arabic’ music-making. In this way we hope better to define the relation of this tradition to the ‘Classical world’, potentially breaking free of Orientalising bias informing modern views. On the other hand, the study and reconstruction, virtual and material, of wind instruments of Hellenistic pedigree but found outside the confinements of the Hellenistic ‘heartlands’ may provide evidence of ‘foreign’ tonality employed in those regions – specifically the royal city of Meroë in modern Sudan and the Oxus Temple in modern Tajikistan.
Summary
From medieval times, Arabic as well as European music was analysed in terms that were inherited from Classical Antiquity and had thus developed in a very different music culture. In spite of recent breakthroughs in the understanding of the latter, whose technicalities we access not only through texts and iconography, but also through instrument finds and surviving notated melodies, its relation to music traditions known from later periods and different places is almost uncharted territory.
The present project explores relations between Hellenic/Hellenistic music as pervaded the theatres and concert halls throughout and beyond the Roman empire, Near Eastern traditions – from the diatonic system emerging from cuneiform sources to the flourishing musical world of the caliphates – and, as far as possible, African musical life south of Egypt as well – a region that maintained close ties both with the Hellenised culture of its northern neighbours and with the Arabian Peninsula.
On the one hand, this demands collaboration between Classical Philology and Arabic Studies, extending methods recently developed within music archaeological research related to the Classical Mediterranean. Arabic writings need to be examined in close reading, using recent insights into the interplay between ancient music theory and practice, in order to segregate the influence of Greek thinking from ideas and facts that must relate to contemporaneous ‘Arabic’ music-making. In this way we hope better to define the relation of this tradition to the ‘Classical world’, potentially breaking free of Orientalising bias informing modern views. On the other hand, the study and reconstruction, virtual and material, of wind instruments of Hellenistic pedigree but found outside the confinements of the Hellenistic ‘heartlands’ may provide evidence of ‘foreign’ tonality employed in those regions – specifically the royal city of Meroë in modern Sudan and the Oxus Temple in modern Tajikistan.
Max ERC Funding
775 959 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym AQUAMS
Project Analysis of quantum many-body systems
Researcher (PI) Robert Seiringer
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Call Details Advanced Grant (AdG), PE1, ERC-2015-AdG
Summary The main focus of this project is the mathematical analysis of many-body quantum systems, in particular, interacting quantum gases at low temperature. The recent experimental advances in studying ultra-cold atomic gases have led to renewed interest in these systems. They display a rich variety of quantum phenomena, including, e.g., Bose–Einstein condensation and superfluidity, which makes them interesting both from a physical and a mathematical point of view.
The goal of this project is the development of new mathematical tools for dealing with complex problems in many-body quantum systems. New mathematical methods lead to different points of view and thus increase our understanding of physical systems. From the point of view of mathematical physics, there has been significant progress in the last few years in understanding the interesting phenomena occurring in quantum gases, and the goal of this project is to investigate some of the key issues that remain unsolved. Due to the complex nature of the problems, new mathematical ideas
and methods will have to be developed for this purpose. One of the main question addressed in this proposal is the validity of the Bogoliubov approximation for the excitation spectrum of many-body quantum systems. While its accuracy has been
successfully shown for the ground state energy of various models, its predictions concerning the excitation spectrum have so far only been verified in the Hartree limit, an extreme form of a mean-field limit where the interaction among the particles is very weak and ranges over the whole system. The central part of this project is concerned with the extension of these results to the case of short-range interactions. Apart from being mathematically much more challenging, the short-range case is the
one most relevant for the description of actual physical systems. Hence progress along these lines can be expected to yield valuable insight into the complex behavior of these many-body quantum systems.
Summary
The main focus of this project is the mathematical analysis of many-body quantum systems, in particular, interacting quantum gases at low temperature. The recent experimental advances in studying ultra-cold atomic gases have led to renewed interest in these systems. They display a rich variety of quantum phenomena, including, e.g., Bose–Einstein condensation and superfluidity, which makes them interesting both from a physical and a mathematical point of view.
The goal of this project is the development of new mathematical tools for dealing with complex problems in many-body quantum systems. New mathematical methods lead to different points of view and thus increase our understanding of physical systems. From the point of view of mathematical physics, there has been significant progress in the last few years in understanding the interesting phenomena occurring in quantum gases, and the goal of this project is to investigate some of the key issues that remain unsolved. Due to the complex nature of the problems, new mathematical ideas
and methods will have to be developed for this purpose. One of the main question addressed in this proposal is the validity of the Bogoliubov approximation for the excitation spectrum of many-body quantum systems. While its accuracy has been
successfully shown for the ground state energy of various models, its predictions concerning the excitation spectrum have so far only been verified in the Hartree limit, an extreme form of a mean-field limit where the interaction among the particles is very weak and ranges over the whole system. The central part of this project is concerned with the extension of these results to the case of short-range interactions. Apart from being mathematically much more challenging, the short-range case is the
one most relevant for the description of actual physical systems. Hence progress along these lines can be expected to yield valuable insight into the complex behavior of these many-body quantum systems.
Max ERC Funding
1 497 755 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym ARCHADAPT
Project The architecture of adaptation to novel environments
Researcher (PI) Christian Werner Schlötterer
Host Institution (HI) VETERINAERMEDIZINISCHE UNIVERSITAET WIEN
Call Details Advanced Grant (AdG), LS8, ERC-2011-ADG_20110310
Summary One of the central goals in evolutionary biology is to understand adaptation. Experimental evolution represents a highly promising approach to study adaptation. In this proposal, a freshly collected D. simulans population will be allowed to adapt to laboratory conditions under two different temperature regimes: hot (27°C) and cold (18°C). The trajectories of adaptation to these novel environments will be monitored on three levels: 1) genomic, 2) transcriptomic, 3) phenotypic. Allele frequency changes during the experiment will be measured by next generation sequencing of DNA pools (Pool-Seq) to identify targets of selection. RNA-Seq will be used to trace adaptation on the transcriptomic level during three developmental stages. Eight different phenotypes will be scored to measure the phenotypic consequences of adaptation. Combining the adaptive trajectories on these three levels will provide a picture of adaptation for a multicellular, outcrossing organism that is far more detailed than any previous results.
Furthermore, the proposal addresses the question of how adaptation on these three levels is reversible if the environment reverts to ancestral conditions. The third aspect of adaptation covered in the proposal is the question of repeatability of adaptation. Again, this question will be addressed on the three levels: genomic, transcriptomic and phenotypic. Using replicates with different degrees of genetic similarity, as well as closely related species, we will test how similar the adaptive response is.
This large-scale study will provide new insights into the importance of standing variation for the adaptation to novel environments. Hence, apart from providing significant evolutionary insights on the trajectories of adaptation, the results we will obtain will have important implications for conservation genetics and commercial breeding.
Summary
One of the central goals in evolutionary biology is to understand adaptation. Experimental evolution represents a highly promising approach to study adaptation. In this proposal, a freshly collected D. simulans population will be allowed to adapt to laboratory conditions under two different temperature regimes: hot (27°C) and cold (18°C). The trajectories of adaptation to these novel environments will be monitored on three levels: 1) genomic, 2) transcriptomic, 3) phenotypic. Allele frequency changes during the experiment will be measured by next generation sequencing of DNA pools (Pool-Seq) to identify targets of selection. RNA-Seq will be used to trace adaptation on the transcriptomic level during three developmental stages. Eight different phenotypes will be scored to measure the phenotypic consequences of adaptation. Combining the adaptive trajectories on these three levels will provide a picture of adaptation for a multicellular, outcrossing organism that is far more detailed than any previous results.
Furthermore, the proposal addresses the question of how adaptation on these three levels is reversible if the environment reverts to ancestral conditions. The third aspect of adaptation covered in the proposal is the question of repeatability of adaptation. Again, this question will be addressed on the three levels: genomic, transcriptomic and phenotypic. Using replicates with different degrees of genetic similarity, as well as closely related species, we will test how similar the adaptive response is.
This large-scale study will provide new insights into the importance of standing variation for the adaptation to novel environments. Hence, apart from providing significant evolutionary insights on the trajectories of adaptation, the results we will obtain will have important implications for conservation genetics and commercial breeding.
Max ERC Funding
2 452 084 €
Duration
Start date: 2012-07-01, End date: 2018-06-30
Project acronym ARIPHYHIMO
Project Arithmetic and physics of Higgs moduli spaces
Researcher (PI) Tamas Hausel
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Call Details Advanced Grant (AdG), PE1, ERC-2012-ADG_20120216
Summary The proposal studies problems concerning the geometry and topology of moduli spaces of Higgs bundles on a Riemann surface motivated by parallel considerations in number theory and mathematical physics. In this way the proposal bridges various duality theories in string theory with the Langlands program in number theory.
The heart of the proposal is a circle of precise conjectures relating to the topology of the moduli space of Higgs bundles. The formulation and motivations of the conjectures make direct contact with the Langlands program in number theory, various duality conjectures in string theory, algebraic combinatorics, knot theory and low dimensional topology and representation theory of quivers, finite groups and algebras of Lie type and Cherednik algebras.
Summary
The proposal studies problems concerning the geometry and topology of moduli spaces of Higgs bundles on a Riemann surface motivated by parallel considerations in number theory and mathematical physics. In this way the proposal bridges various duality theories in string theory with the Langlands program in number theory.
The heart of the proposal is a circle of precise conjectures relating to the topology of the moduli space of Higgs bundles. The formulation and motivations of the conjectures make direct contact with the Langlands program in number theory, various duality conjectures in string theory, algebraic combinatorics, knot theory and low dimensional topology and representation theory of quivers, finite groups and algebras of Lie type and Cherednik algebras.
Max ERC Funding
1 304 945 €
Duration
Start date: 2013-04-01, End date: 2018-08-31
Project acronym CATCHIT
Project Coherently Advanced Tissue and Cell Holographic Imaging and Trapping
Researcher (PI) Monika Ritsch-Marte
Host Institution (HI) MEDIZINISCHE UNIVERSITAT INNSBRUCK
Call Details Advanced Grant (AdG), PE2, ERC-2009-AdG
Summary We envisage a new generation of dynamic holographic laser tweezers and stretching tools with unprecedented spatial control of gradient and scattering light forces, to unravel functional mysteries of cell biology and genetics: Based on our recently developed, highly successful and widely recognized amplitude and phase shaping techniques with cascaded spatial light modulators (SLM), we will create new holographic optical manipulators consisting of a line-shaped trap with balanced net scattering forces and controllable local phase-gradients. Combining these line stretchers with spiral phase contrast imaging or nonlinear optical microscopy will allow quantitative study of functional shape changes. The novel tool is hugely more versatile than standard optical tweezers, since direction and magnitude of the scattering force can be designed to precisely follow the structure. In combination with conventional multi-spot traps the line stretcher acts as a sensitive and adaptable local force sensor. In collaboration with local experts we want to tackle hot topics in Genetics, e.g. search for force profile signatures in regions with Copy Number Variations. Possibly the approach may shed light on basic physical characteristics such as, for example, chromosomal fragility in Fra(X) syndrome, the most common monogenic cause of mental retardation. The new design intrinsically offers enhanced microscopic resolution, as SLM-synthesized apertures and waveforms can enlarge the number of spatial frequencies forming the image. Ultimately, nonlinear holography can be implemented, sending phase shaped wavefronts to target samples. This can, e.g., be used to push the sensitivity of nonlinear chemical imaging, or for controlled photo-activation of targeted regions in neurons.
Summary
We envisage a new generation of dynamic holographic laser tweezers and stretching tools with unprecedented spatial control of gradient and scattering light forces, to unravel functional mysteries of cell biology and genetics: Based on our recently developed, highly successful and widely recognized amplitude and phase shaping techniques with cascaded spatial light modulators (SLM), we will create new holographic optical manipulators consisting of a line-shaped trap with balanced net scattering forces and controllable local phase-gradients. Combining these line stretchers with spiral phase contrast imaging or nonlinear optical microscopy will allow quantitative study of functional shape changes. The novel tool is hugely more versatile than standard optical tweezers, since direction and magnitude of the scattering force can be designed to precisely follow the structure. In combination with conventional multi-spot traps the line stretcher acts as a sensitive and adaptable local force sensor. In collaboration with local experts we want to tackle hot topics in Genetics, e.g. search for force profile signatures in regions with Copy Number Variations. Possibly the approach may shed light on basic physical characteristics such as, for example, chromosomal fragility in Fra(X) syndrome, the most common monogenic cause of mental retardation. The new design intrinsically offers enhanced microscopic resolution, as SLM-synthesized apertures and waveforms can enlarge the number of spatial frequencies forming the image. Ultimately, nonlinear holography can be implemented, sending phase shaped wavefronts to target samples. This can, e.g., be used to push the sensitivity of nonlinear chemical imaging, or for controlled photo-activation of targeted regions in neurons.
Max ERC Funding
1 987 428 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym CDK6-DrugOpp
Project CDK6 in transcription - turning a foe in a friend
Researcher (PI) Veronika SEXL
Host Institution (HI) VETERINAERMEDIZINISCHE UNIVERSITAET WIEN
Call Details Advanced Grant (AdG), LS7, ERC-2015-AdG
Summary "Translational research aims at applying mechanistic understanding in the development of "precision medicine", which depends on precise diagnostic tools and therapeutic approaches. Cancer therapy is experiencing a switch from non-specific, cytotoxic agents towards molecularly targeted and rationally designed compounds with the promise of greater efficacy and fewer side effects.
The two cell-cycle kinases CDK4 and CDK6 normally facilitate cell-cycle progression but are abnormally activated in certain cancers. CDK6 is up-regulated in hematopoietic malignancies, where it is the predominant cell-cycle kinase. The importance of CDK4/6 for tumor development is underscored by the fact that the US FDA selected inhibitors of the kinase activity of CDK4/6 as "breakthrough of the year 2013". Our recent findings suggest that the effects of the inhibitors may be limited as CDK6 is not only involved in cell-cycle progression: ground-breaking research in my group and others has shown that CDK6 is involved in regulation of transcription in a kinase-independent manner thereby driving the proliferation of leukemic stem cells and tumor formation. We have now identified mutations in CDK6 that convert it from a tumor promoter into a tumor suppressor. This unexpected outcome is accompanied by a distinct transcriptional profile. Separating the tumor-promoting from the tumor suppressive functions may open a novel therapeutic avenue for drug development. We aim at understanding which domains and residues of CDK6 are involved in rewiring the transcriptional landscape to pave the way for sophisticated inhibitors. The idea of turning a cancer cell's own most potent weapon against itself is novel and would represent a new paradigm for drug design. Finally, the understanding of CDK6 functions in tumor promotion and maintenance will also result in better patient stratification and improved treatment decisions for a broad spectrum of cancer types."
Summary
"Translational research aims at applying mechanistic understanding in the development of "precision medicine", which depends on precise diagnostic tools and therapeutic approaches. Cancer therapy is experiencing a switch from non-specific, cytotoxic agents towards molecularly targeted and rationally designed compounds with the promise of greater efficacy and fewer side effects.
The two cell-cycle kinases CDK4 and CDK6 normally facilitate cell-cycle progression but are abnormally activated in certain cancers. CDK6 is up-regulated in hematopoietic malignancies, where it is the predominant cell-cycle kinase. The importance of CDK4/6 for tumor development is underscored by the fact that the US FDA selected inhibitors of the kinase activity of CDK4/6 as "breakthrough of the year 2013". Our recent findings suggest that the effects of the inhibitors may be limited as CDK6 is not only involved in cell-cycle progression: ground-breaking research in my group and others has shown that CDK6 is involved in regulation of transcription in a kinase-independent manner thereby driving the proliferation of leukemic stem cells and tumor formation. We have now identified mutations in CDK6 that convert it from a tumor promoter into a tumor suppressor. This unexpected outcome is accompanied by a distinct transcriptional profile. Separating the tumor-promoting from the tumor suppressive functions may open a novel therapeutic avenue for drug development. We aim at understanding which domains and residues of CDK6 are involved in rewiring the transcriptional landscape to pave the way for sophisticated inhibitors. The idea of turning a cancer cell's own most potent weapon against itself is novel and would represent a new paradigm for drug design. Finally, the understanding of CDK6 functions in tumor promotion and maintenance will also result in better patient stratification and improved treatment decisions for a broad spectrum of cancer types."
Max ERC Funding
2 497 520 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym CohesinMolMech
Project Molecular mechanisms of cohesin-mediated sister chromatid cohesion and chromatin organization
Researcher (PI) Jan-Michael Peters
Host Institution (HI) FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
Call Details Advanced Grant (AdG), LS1, ERC-2015-AdG
Summary During S-phase newly synthesized “sister” DNA molecules become physically connected. This sister chromatid cohesion resists the pulling forces of the mitotic spindle and thereby enables the bi-orientation and subsequent symmetrical segregation of chromosomes. Cohesion is mediated by ring-shaped cohesin complexes, which are thought to entrap sister DNA molecules topologically. In mammalian cells, cohesin is loaded onto DNA at the end of mitosis by the Scc2-Scc4 complex, becomes acetylated during S-phase, and is stably “locked” on DNA during S- and G2-phase by sororin. Sororin stabilizes cohesin on DNA by inhibiting Wapl, which can otherwise release cohesin from DNA again. In addition to mediating cohesion, cohesin also has important roles in organizing higher-order chromatin structures and in gene regulation. Cohesin performs the latter functions in both proliferating and post-mitotic cells and mediates at least some of these together with the sequence-specific DNA-binding protein CTCF, which co-localizes with cohesin at many genomic sites. Although cohesin and CTCF perform essential functions in mammalian cells, it is poorly understood how cohesin is loaded onto DNA by Scc2-Scc4, how cohesin is positioned in the genome, how cohesin is released from DNA again by Wapl, and how Wapl is inhibited by sororin. Likewise, it is not known how cohesin establishes cohesion during DNA replication and how cohesin cooperates with CTCF to organize chromatin structure. Here we propose to address these questions by combining biochemical reconstitution, single-molecule TIRF microscopy, genetic and cell biological approaches. We expect that the results of these studies will advance our understanding of cell division, chromatin structure and gene regulation, and may also provide insight into the etiology of disorders that are caused by cohesin dysfunction, such as Down syndrome and “cohesinopathies” or cancers, in which cohesin mutations have been found to occur frequently.
Summary
During S-phase newly synthesized “sister” DNA molecules become physically connected. This sister chromatid cohesion resists the pulling forces of the mitotic spindle and thereby enables the bi-orientation and subsequent symmetrical segregation of chromosomes. Cohesion is mediated by ring-shaped cohesin complexes, which are thought to entrap sister DNA molecules topologically. In mammalian cells, cohesin is loaded onto DNA at the end of mitosis by the Scc2-Scc4 complex, becomes acetylated during S-phase, and is stably “locked” on DNA during S- and G2-phase by sororin. Sororin stabilizes cohesin on DNA by inhibiting Wapl, which can otherwise release cohesin from DNA again. In addition to mediating cohesion, cohesin also has important roles in organizing higher-order chromatin structures and in gene regulation. Cohesin performs the latter functions in both proliferating and post-mitotic cells and mediates at least some of these together with the sequence-specific DNA-binding protein CTCF, which co-localizes with cohesin at many genomic sites. Although cohesin and CTCF perform essential functions in mammalian cells, it is poorly understood how cohesin is loaded onto DNA by Scc2-Scc4, how cohesin is positioned in the genome, how cohesin is released from DNA again by Wapl, and how Wapl is inhibited by sororin. Likewise, it is not known how cohesin establishes cohesion during DNA replication and how cohesin cooperates with CTCF to organize chromatin structure. Here we propose to address these questions by combining biochemical reconstitution, single-molecule TIRF microscopy, genetic and cell biological approaches. We expect that the results of these studies will advance our understanding of cell division, chromatin structure and gene regulation, and may also provide insight into the etiology of disorders that are caused by cohesin dysfunction, such as Down syndrome and “cohesinopathies” or cancers, in which cohesin mutations have been found to occur frequently.
Max ERC Funding
2 500 000 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym COMBINE
Project From flies to humans combining whole genome screens and tissue specific gene targeting to identify novel pathways involved in cancer and metastases
Researcher (PI) Josef Martin Penninger
Host Institution (HI) INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH
Call Details Advanced Grant (AdG), LS4, ERC-2008-AdG
Summary Cancer care will be revolutionized over the next decade by the introduction of novel therapeutics that target the underlying molecular mechanisms of the disease. With the advent of human genetics, a plethora of genes have been correlated with human diseases such as cancer the SNP maps. Since the sequences are now available, the next big challenge is to determine the function of these genes in the context of the entire organism. Genetic animal models have proven to be extremely valuable to elucidate the essential functions of genes in normal physiology and the pathogenesis of disease. Using gene-targeted mice we have previously identified RANKL as a master gene of bone loss in arthritis, osteoporosis, and cancer cell migration and metastases and genes that control heart and kidney function; wound healing; diabetes; or lung injury Our primary goal is to use functional genomics in Drosophila and mice to understand cell transformation, invasion, and cancer metastases of epithelial tumors. The following projects are proposed: 1. Role of the key osteoclast differentiation factors RANKL-RANK and its downstream signalling cascade in the development of breast and prostate cancer. 2. Requirement of osteoclasts for bone metastases and stem cell niches using a new RANKfloxed allele; function of RANKL-RANK in local tumor cell invasion. 3. Role of RANKL-RANK in the central fever response to understand potential implications of future RANKL-RANK directed therapies. 4. Integration of gene targeting in mice with state-of-the art technologies in fly genetics; use of whole genome tissue-specific in vivo RNAi Drosophila libraries to identify essential and novel pathways for cancer pathogenesis using whole genome screens. 5. Role of TSPAN6, as a candidate lung metastasis gene. Identification of new cancer disease genes will allow us to design novel strategies for cancer treatment and will have ultimately impact on the basic understanding of cancer, metastases, and human health.
Summary
Cancer care will be revolutionized over the next decade by the introduction of novel therapeutics that target the underlying molecular mechanisms of the disease. With the advent of human genetics, a plethora of genes have been correlated with human diseases such as cancer the SNP maps. Since the sequences are now available, the next big challenge is to determine the function of these genes in the context of the entire organism. Genetic animal models have proven to be extremely valuable to elucidate the essential functions of genes in normal physiology and the pathogenesis of disease. Using gene-targeted mice we have previously identified RANKL as a master gene of bone loss in arthritis, osteoporosis, and cancer cell migration and metastases and genes that control heart and kidney function; wound healing; diabetes; or lung injury Our primary goal is to use functional genomics in Drosophila and mice to understand cell transformation, invasion, and cancer metastases of epithelial tumors. The following projects are proposed: 1. Role of the key osteoclast differentiation factors RANKL-RANK and its downstream signalling cascade in the development of breast and prostate cancer. 2. Requirement of osteoclasts for bone metastases and stem cell niches using a new RANKfloxed allele; function of RANKL-RANK in local tumor cell invasion. 3. Role of RANKL-RANK in the central fever response to understand potential implications of future RANKL-RANK directed therapies. 4. Integration of gene targeting in mice with state-of-the art technologies in fly genetics; use of whole genome tissue-specific in vivo RNAi Drosophila libraries to identify essential and novel pathways for cancer pathogenesis using whole genome screens. 5. Role of TSPAN6, as a candidate lung metastasis gene. Identification of new cancer disease genes will allow us to design novel strategies for cancer treatment and will have ultimately impact on the basic understanding of cancer, metastases, and human health.
Max ERC Funding
2 499 465 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym CoMoQuant
Project Correlated Molecular Quantum Gases in Optical Lattices
Researcher (PI) Hanns-Christoph NAEGERL
Host Institution (HI) UNIVERSITAET INNSBRUCK
Call Details Advanced Grant (AdG), PE2, ERC-2017-ADG
Summary In a quantum engineering approach we aim to create strongly correlated molecular quantum gases for polar molecules confined in an optical lattice to two-dimensional geometry with full quantum control of all de-grees of freedom with single molecule control and detection. The goal is to synthesize a high-fidelity molec-ular quantum simulator with thousands of particles and to carry out experiments on phases and dynamics of strongly-correlated quantum matter in view of strong long-range dipolar interactions. Our choice of mole-cule is the KCs dimer, which can either be a boson or a fermion, allowing us to prepare and probe bosonic as well as fermionic dipolar quantum matter in two dimensions. Techniques such as quantum-gas microscopy, perfectly suited for two-dimensional systems, will be applied to the molecular samples for local control and local readout.
The low-entropy molecular samples are created out of quantum degenerate atomic samples by well-established coherent atom paring and coherent optical ground-state transfer techniques. Crucial to this pro-posal is the full control over the molecular sample. To achieve near-unity lattice filling fraction for the mo-lecular samples, we create two-dimensional samples of K-Cs atom pairs as precursors to molecule formation by merging parallel planar systems of K and Cs, which are either in a band-insulating state (for the fermions) or in Mott-insulating state (for the bosons), along the out-of-plane direction.
The polar molecular samples are used to perform quantum simulations on ground-state properties and dy-namical properties of quantum many-body spin systems. We aim to create novel forms of superfluidity, to investigate into novel quantum many-body phases in the lattice that arise from the long-range molecular dipole-dipole interaction, and to probe quantum magnetism and its dynamics such as spin transport with single-spin control and readout. In addition, disorder can be engineered to mimic real physical situations.
Summary
In a quantum engineering approach we aim to create strongly correlated molecular quantum gases for polar molecules confined in an optical lattice to two-dimensional geometry with full quantum control of all de-grees of freedom with single molecule control and detection. The goal is to synthesize a high-fidelity molec-ular quantum simulator with thousands of particles and to carry out experiments on phases and dynamics of strongly-correlated quantum matter in view of strong long-range dipolar interactions. Our choice of mole-cule is the KCs dimer, which can either be a boson or a fermion, allowing us to prepare and probe bosonic as well as fermionic dipolar quantum matter in two dimensions. Techniques such as quantum-gas microscopy, perfectly suited for two-dimensional systems, will be applied to the molecular samples for local control and local readout.
The low-entropy molecular samples are created out of quantum degenerate atomic samples by well-established coherent atom paring and coherent optical ground-state transfer techniques. Crucial to this pro-posal is the full control over the molecular sample. To achieve near-unity lattice filling fraction for the mo-lecular samples, we create two-dimensional samples of K-Cs atom pairs as precursors to molecule formation by merging parallel planar systems of K and Cs, which are either in a band-insulating state (for the fermions) or in Mott-insulating state (for the bosons), along the out-of-plane direction.
The polar molecular samples are used to perform quantum simulations on ground-state properties and dy-namical properties of quantum many-body spin systems. We aim to create novel forms of superfluidity, to investigate into novel quantum many-body phases in the lattice that arise from the long-range molecular dipole-dipole interaction, and to probe quantum magnetism and its dynamics such as spin transport with single-spin control and readout. In addition, disorder can be engineered to mimic real physical situations.
Max ERC Funding
2 356 117 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
