Project acronym CENDUP
Project Decoding the mechanisms of centrosome duplication
Researcher (PI) Pierre Goenczy
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Country Switzerland
Call Details Advanced Grant (AdG), LS3, ERC-2008-AdG
Summary Centrosome duplication entails the formation of a single procentriole next to each centriole once per cell cycle. The mechanisms governing procentriole formation are poorly understood and constitute a fundamental open question in cell biology. We will launch an innovative multidisciplinary research program to gain significant insight into these mechanisms using C. elegans and human cells. This research program is also expected to have a significant impact by contributing important novel assays to the field. Six specific aims will be pursued: 1) SAS-6 as a ZYG-1 substrate: mechanisms of procentriole formation in C. elegans. We will test in vivo the consequence of SAS-6 phosphorylation by ZYG-1. 2) Biochemical and structural analysis of SAS-6-containing macromolecular complexes (SAMACs). We will isolate and characterize SAMACs from C. elegans embryos and human cells, and analyze their structure using single-particle electron microscopy. 3) Novel cell-free assay for procentriole formation in human cells. We will develop such an assay and use it to test whether SAMACs can direct procentriole formation and whether candidate proteins are needed at centrioles or in the cytoplasm. 4) Mapping interactions between centriolar proteins in live human cells. We will use chemical methods developed by our collaborators to probe interactions between HsSAS-6 and centriolar proteins in a time- and space-resolved manner. 5) Functional genomic and chemical genetic screens in human cells. We will conduct high-throughput fluorescence-based screens in human cells to identify novel genes required for procentriole formation and small molecule inhibitors of this process. 6) Mechanisms underlying differential centriolar maintenance in the germline. In C. elegans, we will characterize how the sas-1 locus is required for centriole maintenance during spermatogenesis, as well as analyze centriole elimination during oogenesis and identify components needed for this process
Summary
Centrosome duplication entails the formation of a single procentriole next to each centriole once per cell cycle. The mechanisms governing procentriole formation are poorly understood and constitute a fundamental open question in cell biology. We will launch an innovative multidisciplinary research program to gain significant insight into these mechanisms using C. elegans and human cells. This research program is also expected to have a significant impact by contributing important novel assays to the field. Six specific aims will be pursued: 1) SAS-6 as a ZYG-1 substrate: mechanisms of procentriole formation in C. elegans. We will test in vivo the consequence of SAS-6 phosphorylation by ZYG-1. 2) Biochemical and structural analysis of SAS-6-containing macromolecular complexes (SAMACs). We will isolate and characterize SAMACs from C. elegans embryos and human cells, and analyze their structure using single-particle electron microscopy. 3) Novel cell-free assay for procentriole formation in human cells. We will develop such an assay and use it to test whether SAMACs can direct procentriole formation and whether candidate proteins are needed at centrioles or in the cytoplasm. 4) Mapping interactions between centriolar proteins in live human cells. We will use chemical methods developed by our collaborators to probe interactions between HsSAS-6 and centriolar proteins in a time- and space-resolved manner. 5) Functional genomic and chemical genetic screens in human cells. We will conduct high-throughput fluorescence-based screens in human cells to identify novel genes required for procentriole formation and small molecule inhibitors of this process. 6) Mechanisms underlying differential centriolar maintenance in the germline. In C. elegans, we will characterize how the sas-1 locus is required for centriole maintenance during spermatogenesis, as well as analyze centriole elimination during oogenesis and identify components needed for this process
Max ERC Funding
2 004 155 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
Project acronym DROSOPHILASIGNALING
Project Signaling Pathways Controlling Patterning, Growth and Final Size of Drosophila Limbs
Researcher (PI) Konrad Basler
Host Institution (HI) University of Zurich
Country Switzerland
Call Details Advanced Grant (AdG), LS3, ERC-2008-AdG
Summary Developmental biology seeks not only to learn more about the fundamental processes of growth and pattern per se, but to understand how they synergize to enable the morphogenesis of multicellular organisms. Our goal is to perform real-time analyses of these developmental processes in an intact developing organ. By applying a vital imaging approach, we can circumvent the normal limitations of inferring cellular dynamics from static images or molecular data, and obtain the real dynamic view of growth and patterning. The wing imaginal disc of Drosophila, which starts out as a simple epithelial structure and gives rise to a precisely structured adult limb, will serve as an ideal model system. This system has the combined advantages of relative simplicity and genetic tractability. We will create several innovations that expand the current toolkit and thus facilitate the detailed dissection of growth and patterning. A key early step will be to develop novel reporters to dynamically and faithfully monitor signaling cascades involved in growth and patterning, such as the Dpp and Hippo pathways. We will also implement quantification techniques that are currently being set up in collaboration with an experimental physicist, to deduce, and alter, the mechanical forces that develop in the cells of a growing tissue. The large amount of quantitative data that will be generated allow us derive computational models of the individual pathways and their interaction. The focus of the study will be to answer the following questions: 1) Is the Hippo pathway regulated spatially and temporally, and by what signaling pathways? 2) Do mechanical forces play a pivotal controlling role in organ morphogenesis? 3) What are the global effects on growth, when pathways controlling patterning, cell competition or compensatory proliferation are perturbed? The proposed project will bring the approaches taken to define the mechanisms underlying and controlling growth and patterning to the next level.
Summary
Developmental biology seeks not only to learn more about the fundamental processes of growth and pattern per se, but to understand how they synergize to enable the morphogenesis of multicellular organisms. Our goal is to perform real-time analyses of these developmental processes in an intact developing organ. By applying a vital imaging approach, we can circumvent the normal limitations of inferring cellular dynamics from static images or molecular data, and obtain the real dynamic view of growth and patterning. The wing imaginal disc of Drosophila, which starts out as a simple epithelial structure and gives rise to a precisely structured adult limb, will serve as an ideal model system. This system has the combined advantages of relative simplicity and genetic tractability. We will create several innovations that expand the current toolkit and thus facilitate the detailed dissection of growth and patterning. A key early step will be to develop novel reporters to dynamically and faithfully monitor signaling cascades involved in growth and patterning, such as the Dpp and Hippo pathways. We will also implement quantification techniques that are currently being set up in collaboration with an experimental physicist, to deduce, and alter, the mechanical forces that develop in the cells of a growing tissue. The large amount of quantitative data that will be generated allow us derive computational models of the individual pathways and their interaction. The focus of the study will be to answer the following questions: 1) Is the Hippo pathway regulated spatially and temporally, and by what signaling pathways? 2) Do mechanical forces play a pivotal controlling role in organ morphogenesis? 3) What are the global effects on growth, when pathways controlling patterning, cell competition or compensatory proliferation are perturbed? The proposed project will bring the approaches taken to define the mechanisms underlying and controlling growth and patterning to the next level.
Max ERC Funding
2 310 000 €
Duration
Start date: 2009-02-01, End date: 2014-01-31
Project acronym FMWK 1870-2008
Project The surfaces of cement and reinforced concrete. A history of the formworks and processing of the surface, 1870-2008
Researcher (PI) Roberto Gargiani
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Country Switzerland
Call Details Advanced Grant (AdG), SH5, ERC-2008-AdG
Summary Since the nineteenth century, the reinforced concrete has been generating a vast specialized litterature everywhere in the world. However, none of it has ever tried to make a first assessment of the evolution of one of the most fundamental element in the processing of the reinforced concrete: the formwork; nor have been reconstructed the various ways of processing the surfaces after removal of the formwork in order to get special effects of polished or rustic surface. Therefore, on the subject of manufacturing of the formworks and processing of the surface, there is a true gap in the studies on reinforced concrete that the research The surfaces of cement and reinforced concrete. A history of the formworks and processing of the surface, 1870-2008 intends to fill. Whether historical or operationnal, this gap lacks not only of the context of the evolution from the nineteenth century, but also of a comprehensive outline of the recent production. The purpose of the research is to provide the most comprehensive documentation and the most significant examples of the international architectural production on the subject of formworks and concrete surfaces within the time span considered. Drawing up the outline of the various types of building and processing of the surfaces will be extraordinarily useful for the historiography of architecture, which will hence have a scientific instrument to evaluate the works in terms of connections between form and material in relation to concrete, as well as for the modern formworks in which the technicial and artistical issues of reinforced concrete processing at sight still remain fundamental. The results of the research will be collected in a book with the caracteristics of an essay, consisting of an important written part and an extremely rich iconographic documentation (project drawings, photographs of building sites and tools, etc.); it will be structured as a synthesis between the technical manual and the historical critical essay.
Summary
Since the nineteenth century, the reinforced concrete has been generating a vast specialized litterature everywhere in the world. However, none of it has ever tried to make a first assessment of the evolution of one of the most fundamental element in the processing of the reinforced concrete: the formwork; nor have been reconstructed the various ways of processing the surfaces after removal of the formwork in order to get special effects of polished or rustic surface. Therefore, on the subject of manufacturing of the formworks and processing of the surface, there is a true gap in the studies on reinforced concrete that the research The surfaces of cement and reinforced concrete. A history of the formworks and processing of the surface, 1870-2008 intends to fill. Whether historical or operationnal, this gap lacks not only of the context of the evolution from the nineteenth century, but also of a comprehensive outline of the recent production. The purpose of the research is to provide the most comprehensive documentation and the most significant examples of the international architectural production on the subject of formworks and concrete surfaces within the time span considered. Drawing up the outline of the various types of building and processing of the surfaces will be extraordinarily useful for the historiography of architecture, which will hence have a scientific instrument to evaluate the works in terms of connections between form and material in relation to concrete, as well as for the modern formworks in which the technicial and artistical issues of reinforced concrete processing at sight still remain fundamental. The results of the research will be collected in a book with the caracteristics of an essay, consisting of an important written part and an extremely rich iconographic documentation (project drawings, photographs of building sites and tools, etc.); it will be structured as a synthesis between the technical manual and the historical critical essay.
Max ERC Funding
660 000 €
Duration
Start date: 2009-03-01, End date: 2015-02-28
Project acronym IPCDP
Project Institutions, Policy and Culture in the Development Process
Researcher (PI) Fabrizio Zilibotti
Host Institution (HI) University of Zurich
Country Switzerland
Call Details Advanced Grant (AdG), SH1, ERC-2008-AdG
Summary This project aims at developing theoretical and empirical research on the structural transformation that accompanies economic development and on the determinants of its success or failure. This transformation involves changes in policies, institutions, and even preferences and social hierarchies. The project consists of four subprojects. Since China represents the most spectacular ongoing episode of economic transition, four of them focus on the Chinese experience, while the remaining ones address general issues in growth and development. The first subproject analyses some puzzling features of China's recent growth experience, such as the coexistence of high growth with increasing capital export, and the falling labour share, with the aid of a theory which emphasises the efficiency gains associated with the reallocation between firms of different productivity. Since changes in income distribution are an important element, and a concern, of the Chinese transition, the three following subprojects focus, respectively, on the crisis of the system of old age insurance, the effects of the rise of the middle class, and the introduction of special economic zones in the 1980s. Two subprojects study different aspects of competition policy in development. The first one focuses on intellectual property right protection, emphasising the link between innovation, technology adoption and human capital accumulation. The second one studies the coordinating role of industrial policy and how its scope changes with development. The last two subprojects focus on culture. The diffusion of preferences and values that foster cooperation rather than conflict is no less important than incentives for technology adoption. Likewise, the rise of an "entrepreneurial spirit" is an engine of growth in the development transition. We plan to study the emergence and cultural transmission of preferences that are conducive to economic growth, and how they interact with the process of structural change.
Summary
This project aims at developing theoretical and empirical research on the structural transformation that accompanies economic development and on the determinants of its success or failure. This transformation involves changes in policies, institutions, and even preferences and social hierarchies. The project consists of four subprojects. Since China represents the most spectacular ongoing episode of economic transition, four of them focus on the Chinese experience, while the remaining ones address general issues in growth and development. The first subproject analyses some puzzling features of China's recent growth experience, such as the coexistence of high growth with increasing capital export, and the falling labour share, with the aid of a theory which emphasises the efficiency gains associated with the reallocation between firms of different productivity. Since changes in income distribution are an important element, and a concern, of the Chinese transition, the three following subprojects focus, respectively, on the crisis of the system of old age insurance, the effects of the rise of the middle class, and the introduction of special economic zones in the 1980s. Two subprojects study different aspects of competition policy in development. The first one focuses on intellectual property right protection, emphasising the link between innovation, technology adoption and human capital accumulation. The second one studies the coordinating role of industrial policy and how its scope changes with development. The last two subprojects focus on culture. The diffusion of preferences and values that foster cooperation rather than conflict is no less important than incentives for technology adoption. Likewise, the rise of an "entrepreneurial spirit" is an engine of growth in the development transition. We plan to study the emergence and cultural transmission of preferences that are conducive to economic growth, and how they interact with the process of structural change.
Max ERC Funding
1 599 996 €
Duration
Start date: 2009-01-01, End date: 2014-06-30
Project acronym NANOIMMUNE
Project Nanoparticle Vaccines: At the interface of bionanotechnology and adaptive immunity
Researcher (PI) Jeffrey Hubbell
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Country Switzerland
Call Details Advanced Grant (AdG), LS6, ERC-2008-AdG
Summary We have recently developed a bionanotechnology approach to vaccination (Reddy et al., Nature Biotechnology, 25, 1159-1164, 2007): degradable polymeric nanoparticles are designed that: (i) are so small that they can enter the lymphatic circulation by biophysical means; (ii) are efficiently taken up by a large fraction of dendritic cells (DCs) that are resident in the lymph node that drains the injection site; (iii) activate the complement cascade and provide a potent, yet safe, activation signal to those DCs; and (iv) thereby induce a potent, Th1 adaptive immune response to antigen bound to the nanoparticles, with the generation of both antibodies and cytotoxic T lymphocytes. In the present project, we focus on next-generation bionanotechnology vaccine platforms for vaccination. We propose three technological advances, and we propose to demonstrate those three advances in definitive models in the mouse. Specifically, we propose to (Specific Aim 1) evaluate the current approach of complement-mediated DC activation in breaking tolerance to a chronic viral infection (hepatitis B virus, HBV, targeting hepatitis B virus surface antigen, HBsAg) and to combine complement as a danger signal with other nanoparticle-borne danger signals to develop an effective bionanotechnological platform for therapeutic antiviral vaccination; (Specific Aim 2) to develop a new, ultrasmall nanoparticle implementation suitable for delivery of DNA to lymph node-resident DCs, also activating them, to enable more efficient DNA vaccination; and (Specific Aim 3) to develop an ultrasmall nanoparticle implementation suitable for delivery of DNA to DCs resident within the sublingual mucosa, also activating them, to enable efficient DNA mucosal vaccination. The Specific Aim addressing the oral mucosa will begin with HBsAg, to allow comparison to other routes of administration, and will then proceed to antigens from influenza A.
Summary
We have recently developed a bionanotechnology approach to vaccination (Reddy et al., Nature Biotechnology, 25, 1159-1164, 2007): degradable polymeric nanoparticles are designed that: (i) are so small that they can enter the lymphatic circulation by biophysical means; (ii) are efficiently taken up by a large fraction of dendritic cells (DCs) that are resident in the lymph node that drains the injection site; (iii) activate the complement cascade and provide a potent, yet safe, activation signal to those DCs; and (iv) thereby induce a potent, Th1 adaptive immune response to antigen bound to the nanoparticles, with the generation of both antibodies and cytotoxic T lymphocytes. In the present project, we focus on next-generation bionanotechnology vaccine platforms for vaccination. We propose three technological advances, and we propose to demonstrate those three advances in definitive models in the mouse. Specifically, we propose to (Specific Aim 1) evaluate the current approach of complement-mediated DC activation in breaking tolerance to a chronic viral infection (hepatitis B virus, HBV, targeting hepatitis B virus surface antigen, HBsAg) and to combine complement as a danger signal with other nanoparticle-borne danger signals to develop an effective bionanotechnological platform for therapeutic antiviral vaccination; (Specific Aim 2) to develop a new, ultrasmall nanoparticle implementation suitable for delivery of DNA to lymph node-resident DCs, also activating them, to enable more efficient DNA vaccination; and (Specific Aim 3) to develop an ultrasmall nanoparticle implementation suitable for delivery of DNA to DCs resident within the sublingual mucosa, also activating them, to enable efficient DNA mucosal vaccination. The Specific Aim addressing the oral mucosa will begin with HBsAg, to allow comparison to other routes of administration, and will then proceed to antigens from influenza A.
Max ERC Funding
2 499 425 €
Duration
Start date: 2009-05-01, End date: 2014-04-30
Project acronym ORGANELL
Project Organelle homeostasis: How are membrane fission and fusion machineries coordinated to regulate size and copy number of a lysosomal compartment?
Researcher (PI) Andreas Mayer
Host Institution (HI) UNIVERSITE DE LAUSANNE
Country Switzerland
Call Details Advanced Grant (AdG), LS3, ERC-2008-AdG
Summary Yeast vacuoles (lysosomes) will serve as an excellent model system: Vacuoles change copy number and size in the cell cycle and upon shifts of media; due to their large diameter (up to 5 µm) these changes can be assayed by fluorescence microscopy and are amenable to genetic screening. Moreover, an in vitro system for vacuole fusion exists and we recently succeeded in reconstituting also cell-free vacuole fission with purified organelles. We will first build an experimental toolkit for vacuole fission to characterize this reaction in detail. Several approaches will be combined: (1) Identification of fission proteins by mutant screening, as well as by candidate approaches, and their localization relative to the fission site; (2) further developing a system reconstituting in vitro fission and efficient methods to quantitate it. (3) creating organelle chips to synchronously study fission on multiple single vacuoles immobilized in a defined orientation. (4) time-resolved confocal microscopy of fission proteins in vivo and in vitro; (5) biochemical characterization of fission protein associations and their changes during fission. These approaches will identify the vacuolar fission apparatus and help to elucidate its functioning. In a second step we will explore how the fission apparatus physically and functionally interacts with the already well-defined vacuolar membrane fusion machinery. We will characterize the impact of cell cycle regulators and signaling pathways on these interactions. These studies will be pioneering in that they will lead us to a comprehensive description of an organelle fission process and of how membrane fission and fusion components are coordinated to control size and copy number of an organelle.
Summary
Yeast vacuoles (lysosomes) will serve as an excellent model system: Vacuoles change copy number and size in the cell cycle and upon shifts of media; due to their large diameter (up to 5 µm) these changes can be assayed by fluorescence microscopy and are amenable to genetic screening. Moreover, an in vitro system for vacuole fusion exists and we recently succeeded in reconstituting also cell-free vacuole fission with purified organelles. We will first build an experimental toolkit for vacuole fission to characterize this reaction in detail. Several approaches will be combined: (1) Identification of fission proteins by mutant screening, as well as by candidate approaches, and their localization relative to the fission site; (2) further developing a system reconstituting in vitro fission and efficient methods to quantitate it. (3) creating organelle chips to synchronously study fission on multiple single vacuoles immobilized in a defined orientation. (4) time-resolved confocal microscopy of fission proteins in vivo and in vitro; (5) biochemical characterization of fission protein associations and their changes during fission. These approaches will identify the vacuolar fission apparatus and help to elucidate its functioning. In a second step we will explore how the fission apparatus physically and functionally interacts with the already well-defined vacuolar membrane fusion machinery. We will characterize the impact of cell cycle regulators and signaling pathways on these interactions. These studies will be pioneering in that they will lead us to a comprehensive description of an organelle fission process and of how membrane fission and fusion components are coordinated to control size and copy number of an organelle.
Max ERC Funding
2 310 000 €
Duration
Start date: 2009-09-01, End date: 2015-08-31
Project acronym PROTEOMICS V3.0
Project Proteomics v3.0: Development, Implementation and Dissemination of a Third Generation Proteomics Technology
Researcher (PI) Rudolf Aebersold
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Advanced Grant (AdG), LS2, ERC-2008-AdG
Summary Quantitative proteomics is a key technology for the life sciences in general and for systems biology in particular. So far, however, technical limitations have made it impossible to analyze the complete proteome of any species. It is the general goal of this proposal to develop, implement, apply and disseminate a new proteomic strategy that has the potential to generate quantitative proteomic datasets at an unprecedented depth, throughput, accuracy and robustness. Specifically, the new technology will identify and quantify every protein in a proteome. The title of the project Proteomics v3.0 was chosen to indicate the transformation of proteomics into its third phase, after 2D gel electrophoresis and LC-MS/MS based shotgun proteomics. Proteomics v3.0 is based on two sequential steps, emulating the strategy that has been immensely successful in the genomic sciences. In the first step the proteomic space is completely mapped out to generate a proteomic resource that is akin to the genomic sequence database. In the second step rapid and accurate assays will be developed to unambiguously identify and quantify any protein of the respective proteome in a multitude of samples. These assays will be made publicly accessible to support quantitative proteomic studies in the respective species. The strategy will first be implemented and tested in the yeast S. cerevisiae. In a later stage of the project it will be extended to the more complicated human proteome and include the development of assays that also probe the state of modification, splice forms and other types of protein variants generated by a specific open reading frame. Overall, the project will transform quantitative proteomics from a highly specialized technology practiced at a high level in a few laboratories worldwide into a commodity technology accessible, in principle to every group.
Summary
Quantitative proteomics is a key technology for the life sciences in general and for systems biology in particular. So far, however, technical limitations have made it impossible to analyze the complete proteome of any species. It is the general goal of this proposal to develop, implement, apply and disseminate a new proteomic strategy that has the potential to generate quantitative proteomic datasets at an unprecedented depth, throughput, accuracy and robustness. Specifically, the new technology will identify and quantify every protein in a proteome. The title of the project Proteomics v3.0 was chosen to indicate the transformation of proteomics into its third phase, after 2D gel electrophoresis and LC-MS/MS based shotgun proteomics. Proteomics v3.0 is based on two sequential steps, emulating the strategy that has been immensely successful in the genomic sciences. In the first step the proteomic space is completely mapped out to generate a proteomic resource that is akin to the genomic sequence database. In the second step rapid and accurate assays will be developed to unambiguously identify and quantify any protein of the respective proteome in a multitude of samples. These assays will be made publicly accessible to support quantitative proteomic studies in the respective species. The strategy will first be implemented and tested in the yeast S. cerevisiae. In a later stage of the project it will be extended to the more complicated human proteome and include the development of assays that also probe the state of modification, splice forms and other types of protein variants generated by a specific open reading frame. Overall, the project will transform quantitative proteomics from a highly specialized technology practiced at a high level in a few laboratories worldwide into a commodity technology accessible, in principle to every group.
Max ERC Funding
2 400 000 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
Project acronym QON
Project Quantum optics using nanostructures: from many-body physics to quantum information processing
Researcher (PI) Atac Imamoglu
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Advanced Grant (AdG), PE3, ERC-2008-AdG
Summary Spins in nanostructures have emerged as a new paradigm for studying quantum optical phenomena in the solid-state. Motivated by potential applications in quantum information processing, the research in this field has focused on isolating a single confined spin from its environment and implementing coherent manipulation. On the other hand, it has been realized that the principal decoherence mechanisms for confined spins, stemming from interactions with nuclear or electron spin reservoirs, are intimately linked to fascinating many-body condensed-matter physics. We propose to use quantum optical techniques to investigate physics of nanostructures in two opposite but equally interesting regimes, where reservoir couplings are either suppressed to facilitate coherent control or enhanced to promote many body effects. The principal focus of our investigation of many-body phenomena will be on the first observation of optical signatures of the Kondo effect arising from exchange coupling between a confined spin and an electron spin reservoir. In addition, we propose to study nonequilibrium dynamics of quantum dot nuclear spins as well as strongly correlated system of interacting polaritons in coupled nano-cavities. To minimize spin decoherence and to implement quantum control, we propose to use nano-cavity assisted optical manipulation of two-electron spin states in double quantum dots; thanks to its resilience against spin decoherence, this system should allow us to realize elementary quantum information tasks such as spin-polarization conversion and spin entanglement. In addition to indium/gallium arsenide based structures, we propose to study semiconducting carbon nanotubes where hyperfine interactions that lead to spin decoherence can be avoided. Our nanotube experiments will focus on understanding the elementary quantum optical properties, with the ultimate goal of demonstrating coherent optical spin manipulation.
Summary
Spins in nanostructures have emerged as a new paradigm for studying quantum optical phenomena in the solid-state. Motivated by potential applications in quantum information processing, the research in this field has focused on isolating a single confined spin from its environment and implementing coherent manipulation. On the other hand, it has been realized that the principal decoherence mechanisms for confined spins, stemming from interactions with nuclear or electron spin reservoirs, are intimately linked to fascinating many-body condensed-matter physics. We propose to use quantum optical techniques to investigate physics of nanostructures in two opposite but equally interesting regimes, where reservoir couplings are either suppressed to facilitate coherent control or enhanced to promote many body effects. The principal focus of our investigation of many-body phenomena will be on the first observation of optical signatures of the Kondo effect arising from exchange coupling between a confined spin and an electron spin reservoir. In addition, we propose to study nonequilibrium dynamics of quantum dot nuclear spins as well as strongly correlated system of interacting polaritons in coupled nano-cavities. To minimize spin decoherence and to implement quantum control, we propose to use nano-cavity assisted optical manipulation of two-electron spin states in double quantum dots; thanks to its resilience against spin decoherence, this system should allow us to realize elementary quantum information tasks such as spin-polarization conversion and spin entanglement. In addition to indium/gallium arsenide based structures, we propose to study semiconducting carbon nanotubes where hyperfine interactions that lead to spin decoherence can be avoided. Our nanotube experiments will focus on understanding the elementary quantum optical properties, with the ultimate goal of demonstrating coherent optical spin manipulation.
Max ERC Funding
2 300 000 €
Duration
Start date: 2008-11-01, End date: 2013-10-31
Project acronym VIRNA
Project Cellular biology of virus infection
Researcher (PI) Ari Helenius
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Advanced Grant (AdG), LS6, ERC-2008-AdG
Summary Viruses are simple, obligatory, intracellular parasites that depend on the host cell for most of the steps in the replication cycle. Not only do they rely on the cells biosynthetic machinery, they exploit cellular processes for signaling, membrane trafficking, intra-cellular transport, nuclear import and export, molecular sorting, transcriptional regulation, etc. To access the full spectrum of host cell functions in the infection of three different viruses in an unbiased and systematic fashion, we will identify the critical host cell proteins needed by monitoring infection in human tissue culture cells after silencing individual genes using genome-wide siRNA libraries and large sub-libraries based on the human genome. The three viruses are vaccinia virus (a poxvirus), human papilloma virus 16, and Uukuniemi virus (a bunyavirus). They are members of important but poorly analyzed pathogen families representing enveloped and nonenveloped viruses, RNA and DNA viruses, viruses that replicate in the nucleus and in the cytosol. The infection assays to be used are fully automated, and make use of high-content microscopic read-outs for infection and virus production. Identification of the viral infectomes , in this way, offers a valuable, new perspective into the complexities of the infection process, and opens wide new areas of basic and applied research. After validation of hits , extensive biochemical and cell biological analysis will be performed on a selected set of host proteins and pathways identified through the infectome analysis. We will determine which steps in the replication cycle are affected, which mechanisms are involved, and which cellular pathways play a role. For detailed analysis, we will focus on mechanisms in entry, uncoating, and early intracellular events. A large spectrum of techniques including live cell imaging and single particle tracking will be used to follow up the screening results with functional and mechanistic studies.
Summary
Viruses are simple, obligatory, intracellular parasites that depend on the host cell for most of the steps in the replication cycle. Not only do they rely on the cells biosynthetic machinery, they exploit cellular processes for signaling, membrane trafficking, intra-cellular transport, nuclear import and export, molecular sorting, transcriptional regulation, etc. To access the full spectrum of host cell functions in the infection of three different viruses in an unbiased and systematic fashion, we will identify the critical host cell proteins needed by monitoring infection in human tissue culture cells after silencing individual genes using genome-wide siRNA libraries and large sub-libraries based on the human genome. The three viruses are vaccinia virus (a poxvirus), human papilloma virus 16, and Uukuniemi virus (a bunyavirus). They are members of important but poorly analyzed pathogen families representing enveloped and nonenveloped viruses, RNA and DNA viruses, viruses that replicate in the nucleus and in the cytosol. The infection assays to be used are fully automated, and make use of high-content microscopic read-outs for infection and virus production. Identification of the viral infectomes , in this way, offers a valuable, new perspective into the complexities of the infection process, and opens wide new areas of basic and applied research. After validation of hits , extensive biochemical and cell biological analysis will be performed on a selected set of host proteins and pathways identified through the infectome analysis. We will determine which steps in the replication cycle are affected, which mechanisms are involved, and which cellular pathways play a role. For detailed analysis, we will focus on mechanisms in entry, uncoating, and early intracellular events. A large spectrum of techniques including live cell imaging and single particle tracking will be used to follow up the screening results with functional and mechanistic studies.
Max ERC Funding
2 498 400 €
Duration
Start date: 2009-02-01, End date: 2014-01-31
