Project acronym BARRAGE
Project Cell compartmentalization, individuation and diversity
Researcher (PI) Yves Barral
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), LS3, ERC-2009-AdG
Summary Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.
Summary
Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.
Max ERC Funding
2 200 000 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym BFTERRA
Project Biogenesis and Functions of Telomeric Repeat-containing RNA
Researcher (PI) Claus Maria Azzalin
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Starting Grant (StG), LS1, ERC-2009-StG
Summary Telomeres are heterochromatic nucleoprotein complexes located at the end of linear eukaryotic chromosomes. Contrarily to a longstanding dogma, we have recently demonstrated that mammalian telomeres are transcribed into TElomeric Repeat containing RNA (TERRA) molecules. TERRA transcripts contain telomeric RNA repeats and are produced at least in part by DNA-dependent RNA polymerase II-mediated transcription of telomeric DNA. TERRA molecules form discrete nuclear foci that co-localize with telomeric heterochromatin in both interphase and transcriptionally inactive metaphase cells. This indicates that TERRA is an integral component of telomeres and suggests that TERRA might participate in maintaining proper telomere heterochromatin. We will use a variety of biochemistry, cell biology, molecular biology and microscopy based approaches applied to cultured mammalian cells and to the yeast Schizosaccharomyces pombe, to achieve four distinct major goals: i) We will over-express or deplete TERRA in mammalian cells in order to characterize the molecular details of putative TERRA-associated functions in maintaining normal telomere structure and function; ii) We will locate TERRA promoter regions on different human chromosome ends; iii) We will generate mammalian cellular systems in which to study artificially seeded telomeres that can be transcribed in an inducible fashion; iv) We will identify physiological regulators of TERRA by analyzing it in mammalian cultured cells where the functions of candidate factors are compromised. In parallel, taking advantage of the recent discovery of TERRA also in fission yeast, we will systematically analyze TERRA levels in fission yeast mutants derived from a complete gene knockout collection. The study of TERRA regulation and function at chromosome ends will strongly contribute to our understanding of how telomeres are maintained and will help to clarify the general functions of mammalian non-coding RNAs.
Summary
Telomeres are heterochromatic nucleoprotein complexes located at the end of linear eukaryotic chromosomes. Contrarily to a longstanding dogma, we have recently demonstrated that mammalian telomeres are transcribed into TElomeric Repeat containing RNA (TERRA) molecules. TERRA transcripts contain telomeric RNA repeats and are produced at least in part by DNA-dependent RNA polymerase II-mediated transcription of telomeric DNA. TERRA molecules form discrete nuclear foci that co-localize with telomeric heterochromatin in both interphase and transcriptionally inactive metaphase cells. This indicates that TERRA is an integral component of telomeres and suggests that TERRA might participate in maintaining proper telomere heterochromatin. We will use a variety of biochemistry, cell biology, molecular biology and microscopy based approaches applied to cultured mammalian cells and to the yeast Schizosaccharomyces pombe, to achieve four distinct major goals: i) We will over-express or deplete TERRA in mammalian cells in order to characterize the molecular details of putative TERRA-associated functions in maintaining normal telomere structure and function; ii) We will locate TERRA promoter regions on different human chromosome ends; iii) We will generate mammalian cellular systems in which to study artificially seeded telomeres that can be transcribed in an inducible fashion; iv) We will identify physiological regulators of TERRA by analyzing it in mammalian cultured cells where the functions of candidate factors are compromised. In parallel, taking advantage of the recent discovery of TERRA also in fission yeast, we will systematically analyze TERRA levels in fission yeast mutants derived from a complete gene knockout collection. The study of TERRA regulation and function at chromosome ends will strongly contribute to our understanding of how telomeres are maintained and will help to clarify the general functions of mammalian non-coding RNAs.
Max ERC Funding
1 602 600 €
Duration
Start date: 2009-10-01, End date: 2014-09-30
Project acronym BIOCARB
Project Carbonate Biomineralization in the Marine Environment: Paleo-climate proxies and the origin of vital effects
Researcher (PI) Anders Meibom
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Advanced Grant (AdG), PE10, ERC-2009-AdG
Summary This interdisciplinary proposal has the objective to greatly enhance our understanding of fundamental biomineralization processes involved in the formation of calcium carbonates by marine organisms, such as corals, foraminifera and bivalves, in order to better understand vital effects. This is essential to the application of these carbonates as proxies for global (paleo-) environmental change. The core of the proposal is an experimental capability that I have pioneered during 2008: Dynamic stable isotopic labeling during formation of carbonate skeletons, tests, and shells, combined with NanoSIMS imaging. The NanoSIMS ion microprobe is a state-of-the-art analytical technology that allows precise elemental and isotopic imaging with a spatial resolution of ~100 nanometers. NanoSIMS imaging of the isotopic label(s) in the resulting biocarbonates and in associated cell-structures will be used to uncover cellular-level transport processes, timescales of formation of different biocarbonate components, as well as trace-elemental and isotopic fractionations. This will uncover the origin of vital effects. With this proposal, I establish a new scientific frontier and guarantee European leadership. The technical and scientific developments resulting from this work are broadly applicable and will radically change scientific ideas about marine carbonate biomineralization and compositional vital effects.
Summary
This interdisciplinary proposal has the objective to greatly enhance our understanding of fundamental biomineralization processes involved in the formation of calcium carbonates by marine organisms, such as corals, foraminifera and bivalves, in order to better understand vital effects. This is essential to the application of these carbonates as proxies for global (paleo-) environmental change. The core of the proposal is an experimental capability that I have pioneered during 2008: Dynamic stable isotopic labeling during formation of carbonate skeletons, tests, and shells, combined with NanoSIMS imaging. The NanoSIMS ion microprobe is a state-of-the-art analytical technology that allows precise elemental and isotopic imaging with a spatial resolution of ~100 nanometers. NanoSIMS imaging of the isotopic label(s) in the resulting biocarbonates and in associated cell-structures will be used to uncover cellular-level transport processes, timescales of formation of different biocarbonate components, as well as trace-elemental and isotopic fractionations. This will uncover the origin of vital effects. With this proposal, I establish a new scientific frontier and guarantee European leadership. The technical and scientific developments resulting from this work are broadly applicable and will radically change scientific ideas about marine carbonate biomineralization and compositional vital effects.
Max ERC Funding
2 182 000 €
Duration
Start date: 2010-07-01, End date: 2015-06-30
Project acronym DHISP
Project Dorsal Horn Interneurons in Sensory Processing
Researcher (PI) Hanns Ulrich Zeilhofer
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary Chronic pain syndromes are to a large extent due to maladaptive plastic changes in the CNS. A CNS area particularly relevant for such changes is the spinal dorsal horn, where inputs from nociceptive and non-nociceptive fibers undergo their first synaptic integration. This area harbors a sophisticated network of interneurons, which function as a gate-control unit for incoming sensory signals. Several different types of interneurons can be distinguished based e.g. on their neurotransmitter and neuropeptide content. Despite more than 40 years of research, our knowledge about the integration of these neurons in dorsal horn circuits and their contribution to sensory processing is still very limited. This proposal aims at a comprehensive characterization of the dorsal horn neuronal network under normal conditions and in chronic pain states with a focus on inhibitory interneurons. A genome-wide analysis of the gene expression profile shall be made from defined dorsal horn interneurons genetically tagged with fluorescent markers and isolated by fluorescence activated cell sorting. A functional characterization of the connectivity of these neurons in spinal cord slices and of their role in in vivo sensory processing shall be achieved with optogenetic tools (channelrhodopsin-2), which permit activation of these neurons with light. Finally, behavioral analyses shall be made in mice after diphteria toxin-mediated ablation of defined interneuron types. All three approaches shall be applied to naïve mice and to mice with inflammatory or neuropathic pain. The results from these studies will improve our understanding of the malfunctioning of sensory processing in chronic pain states and will provide the basis for novel approaches to the prevention or reversal of chronic pain states.
Summary
Chronic pain syndromes are to a large extent due to maladaptive plastic changes in the CNS. A CNS area particularly relevant for such changes is the spinal dorsal horn, where inputs from nociceptive and non-nociceptive fibers undergo their first synaptic integration. This area harbors a sophisticated network of interneurons, which function as a gate-control unit for incoming sensory signals. Several different types of interneurons can be distinguished based e.g. on their neurotransmitter and neuropeptide content. Despite more than 40 years of research, our knowledge about the integration of these neurons in dorsal horn circuits and their contribution to sensory processing is still very limited. This proposal aims at a comprehensive characterization of the dorsal horn neuronal network under normal conditions and in chronic pain states with a focus on inhibitory interneurons. A genome-wide analysis of the gene expression profile shall be made from defined dorsal horn interneurons genetically tagged with fluorescent markers and isolated by fluorescence activated cell sorting. A functional characterization of the connectivity of these neurons in spinal cord slices and of their role in in vivo sensory processing shall be achieved with optogenetic tools (channelrhodopsin-2), which permit activation of these neurons with light. Finally, behavioral analyses shall be made in mice after diphteria toxin-mediated ablation of defined interneuron types. All three approaches shall be applied to naïve mice and to mice with inflammatory or neuropathic pain. The results from these studies will improve our understanding of the malfunctioning of sensory processing in chronic pain states and will provide the basis for novel approaches to the prevention or reversal of chronic pain states.
Max ERC Funding
2 467 000 €
Duration
Start date: 2010-05-01, End date: 2016-04-30
Project acronym DURABLERESISTANCE
Project Durable resistance against fungal plant pathogens
Researcher (PI) Beat Keller
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Advanced Grant (AdG), LS9, ERC-2009-AdG
Summary Plants and their pathogens are in a constant process of co-evolution. Consequently, many of the known defense genes of plants against fungal pathogens are rapidly loosing effectiveness under agricultural conditions. However, there are examples for durable resistance. It is one of the main research questions in plant biology to determine the genetic basis of such naturally occurring resistance and to understand the underlying biochemical and molecular cause for durability. This durability is characterized by the apparent inability of the pathogen to adapt to the resistance mechanism. The molecular understanding of durable resistance will contribute to future attempts to develop such resistance by design. We want to use two approaches towards understanding and developing durable resistance: the first one is based on the naturally occurring durable resistance gene Lr34 against rust and mildew diseases in wheat. This gene was recently isolated in our group and it encodes a putative ABC type of transporter protein, providing a possible link between non-host and durable resistance. Its function in resistance will be studied by genetic and biochemical approaches in the crop plant wheat, as there is no Lr34-type of resistance characterized in any other plant. However, there is a close Lr34-homolog in rice and its function will be investigated in this diploid system. The second approach will be based on natural diversity found in a specific resistance gene, conferring strong, but not durable resistance. This diversity will be used for a designed improvement of durability by developing new proteins or protein combinations to which the pathogen can not adapt. We will use the 15 naturally occurring alleles of the Pm3 powdery mildew resistance genes to identify the structural basis of specific interactions. Based on this characterization, we will develop intragenic or gene combination pyramiding strategies to obtain more broad-spectrum and more durable resistance.
Summary
Plants and their pathogens are in a constant process of co-evolution. Consequently, many of the known defense genes of plants against fungal pathogens are rapidly loosing effectiveness under agricultural conditions. However, there are examples for durable resistance. It is one of the main research questions in plant biology to determine the genetic basis of such naturally occurring resistance and to understand the underlying biochemical and molecular cause for durability. This durability is characterized by the apparent inability of the pathogen to adapt to the resistance mechanism. The molecular understanding of durable resistance will contribute to future attempts to develop such resistance by design. We want to use two approaches towards understanding and developing durable resistance: the first one is based on the naturally occurring durable resistance gene Lr34 against rust and mildew diseases in wheat. This gene was recently isolated in our group and it encodes a putative ABC type of transporter protein, providing a possible link between non-host and durable resistance. Its function in resistance will be studied by genetic and biochemical approaches in the crop plant wheat, as there is no Lr34-type of resistance characterized in any other plant. However, there is a close Lr34-homolog in rice and its function will be investigated in this diploid system. The second approach will be based on natural diversity found in a specific resistance gene, conferring strong, but not durable resistance. This diversity will be used for a designed improvement of durability by developing new proteins or protein combinations to which the pathogen can not adapt. We will use the 15 naturally occurring alleles of the Pm3 powdery mildew resistance genes to identify the structural basis of specific interactions. Based on this characterization, we will develop intragenic or gene combination pyramiding strategies to obtain more broad-spectrum and more durable resistance.
Max ERC Funding
2 100 000 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
Project acronym DYNALLO
Project Towards a Dynamical Understanding of Allostery
Researcher (PI) Peter Hamm
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Advanced Grant (AdG), PE4, ERC-2009-AdG
Summary Allostery is a fundamental concept Nature uses to regulate the affinity of a certain substrate to an active site of a protein by binding a ligand to a distant allosteric site. We will design experimental tools to gain an atomistic understanding of the conformational transitions that give rise to allostery. We will approach the problem from two distinctively different directions. First, we will initiate conformational transitions of proteins that per se are not photoswitchable, by cross-linking two sites of an allosteric protein with a photo-switchable azobenzene-moiety to initiate a conformational transition similar to ligand binding. We will use ultrafast infrared spectroscopy to time-resolve the conformational transition. Second, we will experimentally verify a frequently expressed hypothesis that allosteric and active site communicate by exchange of vibrational energy. To that end, we will design a versatile approach that allows us to locally deposit vibrational energy at essentially any site in a protein (e.g. through pumping of an optical chromophore that undergoes ultrafast internal conversion), and to detect its appearance at any other site by using vibrational transitions as local thermometers. Thereby, we will map out a network of connectivity in a given protein. Both approaches will applied both to one and the same protein family. One concrete example are PDZ domains, which are among the smallest allosteric proteins, and for which the connection between allostery and vibrational energy flow has been made explicit, based on computer simulations. We will eventually test this hypothesis experimentally, and provide the foundation for a description of allostery that is on an equal footing as our current understanding of protein folding.
Summary
Allostery is a fundamental concept Nature uses to regulate the affinity of a certain substrate to an active site of a protein by binding a ligand to a distant allosteric site. We will design experimental tools to gain an atomistic understanding of the conformational transitions that give rise to allostery. We will approach the problem from two distinctively different directions. First, we will initiate conformational transitions of proteins that per se are not photoswitchable, by cross-linking two sites of an allosteric protein with a photo-switchable azobenzene-moiety to initiate a conformational transition similar to ligand binding. We will use ultrafast infrared spectroscopy to time-resolve the conformational transition. Second, we will experimentally verify a frequently expressed hypothesis that allosteric and active site communicate by exchange of vibrational energy. To that end, we will design a versatile approach that allows us to locally deposit vibrational energy at essentially any site in a protein (e.g. through pumping of an optical chromophore that undergoes ultrafast internal conversion), and to detect its appearance at any other site by using vibrational transitions as local thermometers. Thereby, we will map out a network of connectivity in a given protein. Both approaches will applied both to one and the same protein family. One concrete example are PDZ domains, which are among the smallest allosteric proteins, and for which the connection between allostery and vibrational energy flow has been made explicit, based on computer simulations. We will eventually test this hypothesis experimentally, and provide the foundation for a description of allostery that is on an equal footing as our current understanding of protein folding.
Max ERC Funding
2 400 000 €
Duration
Start date: 2010-02-01, End date: 2015-07-31
Project acronym ELECSPECIONS
Project Electronic spectra of cold, large interstellar ions
Researcher (PI) John Paul Maier
Host Institution (HI) UNIVERSITAT BASEL
Call Details Advanced Grant (AdG), PE4, ERC-2009-AdG
Summary The purpose of this project is to measure for the first time gas-phase spectra of large carbon containing cations, at low temperatures, which are of astrophysical importance. Knowledge of electronic spectroscopy of such molecules is also of pertinence in a number of areas of chemistry and physics, enabling their identification in planetary atmospheres, flames and plasmas and as intermediates in chemical reaction dynamics. This project is interdisciplinary, bridging the areas of chemistry, physics, and astrophysics. It encompasses state of the art techniques of chemical physics and aims at obtaining information to solve the long standing enigma in observational astronomy, the identification of some of the molecules causing absorption of starlight in diffuse interstellar clouds. The project uses ion trapping technology, whereby mass-selected species are held in a radio-frequency field and the vibrations and rotations are relaxed by collisions with cold helium to typical interstellar temperatures of 10-30 K. The electronic spectra of a number of cations, selected on the basis of their special properties including those of bare carbon chains, rings and fullerenes, polycyclic aromatic hydrocarbon cations and their protonated forms will be measured using new detection schemes. The first approach is based on photo-induced charge transfer which is turned on upon laser excitation and the second uses the possibility of rare-gas complexation in the ground but not excited state.
Summary
The purpose of this project is to measure for the first time gas-phase spectra of large carbon containing cations, at low temperatures, which are of astrophysical importance. Knowledge of electronic spectroscopy of such molecules is also of pertinence in a number of areas of chemistry and physics, enabling their identification in planetary atmospheres, flames and plasmas and as intermediates in chemical reaction dynamics. This project is interdisciplinary, bridging the areas of chemistry, physics, and astrophysics. It encompasses state of the art techniques of chemical physics and aims at obtaining information to solve the long standing enigma in observational astronomy, the identification of some of the molecules causing absorption of starlight in diffuse interstellar clouds. The project uses ion trapping technology, whereby mass-selected species are held in a radio-frequency field and the vibrations and rotations are relaxed by collisions with cold helium to typical interstellar temperatures of 10-30 K. The electronic spectra of a number of cations, selected on the basis of their special properties including those of bare carbon chains, rings and fullerenes, polycyclic aromatic hydrocarbon cations and their protonated forms will be measured using new detection schemes. The first approach is based on photo-induced charge transfer which is turned on upon laser excitation and the second uses the possibility of rare-gas complexation in the ground but not excited state.
Max ERC Funding
1 898 624 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym ESEI
Project Engineering Social and Economic Institutions
Researcher (PI) Jacob Goeree
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Advanced Grant (AdG), SH1, ERC-2009-AdG
Summary The advent of the Internet and the increased power of modern day computing have dramatically changed the economic landscape. Billions of dollars worth of goods are being auctioned among geographically dispersed buyers; online brokerages are used to find jobs, trade stocks, make travel arrangements, etc. The architecture of these online (trading) platforms is typically rooted in their pre-Internet counterparts, and advances in the theory of market design combined with increased computing capabilities prompt a careful re-evaluation. This proposal concerns the creation of novel, more flexible institutions using an approach that combines theory, laboratory experiments, and practical policy. The first project enhances our understanding of newly designed package auctions by developing equilibrium models of competitive bidding and measuring the efficacy of alternative formats in controlled experiments. The next project studies novel market forms that allow for all-or-nothing trades to alleviate inefficiencies and enhance dynamic stability when complementarities exist. The third project concerns the design of market regulation and procurement contests to create better incentives for research and development. The fourth project addresses information aggregation properties of alternative voting institutions, suggesting improvements for referenda and jury/committee voting. The Internet has also dramatically altered the nature of social interactions. Emerging institutions such as online social networking tools, rating systems, and web-community Q&A services reduce social distances and catalyze opportunities for social learning. The final project focuses on social learning in a variety of settings and on the impact of social networks on behavior. Combined these projects generate insights that apply to a broad array of social and economic environments and that will guide practitioners to the use of better designed institutions.
Summary
The advent of the Internet and the increased power of modern day computing have dramatically changed the economic landscape. Billions of dollars worth of goods are being auctioned among geographically dispersed buyers; online brokerages are used to find jobs, trade stocks, make travel arrangements, etc. The architecture of these online (trading) platforms is typically rooted in their pre-Internet counterparts, and advances in the theory of market design combined with increased computing capabilities prompt a careful re-evaluation. This proposal concerns the creation of novel, more flexible institutions using an approach that combines theory, laboratory experiments, and practical policy. The first project enhances our understanding of newly designed package auctions by developing equilibrium models of competitive bidding and measuring the efficacy of alternative formats in controlled experiments. The next project studies novel market forms that allow for all-or-nothing trades to alleviate inefficiencies and enhance dynamic stability when complementarities exist. The third project concerns the design of market regulation and procurement contests to create better incentives for research and development. The fourth project addresses information aggregation properties of alternative voting institutions, suggesting improvements for referenda and jury/committee voting. The Internet has also dramatically altered the nature of social interactions. Emerging institutions such as online social networking tools, rating systems, and web-community Q&A services reduce social distances and catalyze opportunities for social learning. The final project focuses on social learning in a variety of settings and on the impact of social networks on behavior. Combined these projects generate insights that apply to a broad array of social and economic environments and that will guide practitioners to the use of better designed institutions.
Max ERC Funding
1 797 525 €
Duration
Start date: 2010-01-01, End date: 2015-12-31
Project acronym EUKARYOTIC RIBOSOME
Project Structural studies of the eukaryotic ribosome by X-ray crystallography
Researcher (PI) Nenad Ban
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), LS1, ERC-2009-AdG
Summary The ribosome is a large cellular organelle that plays a central role in the process of protein synthesis in all organisms. Currently, structural information at atomic resolution exists only for bacterial ribosomes and some of their functional complexes. Eukaryotic ribosomes are larger and significantly more complex than their bacterial counterparts. They consist of two unequal subunits with a combined molecular weight of approximately 4 million Daltons and contain 70-80 different protein molecules and four different RNAs. Currently the only structural information on eukaryotic ribosomes is available from cryo electron microscopic reconstructions in the nanometer resolution range, which is insufficient to derive information about the function of the eukaryotic ribosome at the atomic level. The aim of this proposal is to use X-ray crystallography to obtain structural and functional information on the eukaryotic ribosome and its functional complexes at high resolution. The key targets of the structural work will be: i) the structure of the small ribosomal subunit, ii) the structure of the large ribosomal subunit, and iii) structures of complexes involved in the initiation of protein synthesis. Besides the obvious fundamental importance of this research for understanding protein synthesis in eukaryotes the proposed studies will also be the prerequisite for understanding the structural basis of the regulation of protein synthesis in normal cells and how it is perturbed in various diseases. Finally, comparing the structures of bacterial and eukaryotic ribosomes is important for understanding the specificity of various clinically used antibiotics for the bacterial ribosome.
Summary
The ribosome is a large cellular organelle that plays a central role in the process of protein synthesis in all organisms. Currently, structural information at atomic resolution exists only for bacterial ribosomes and some of their functional complexes. Eukaryotic ribosomes are larger and significantly more complex than their bacterial counterparts. They consist of two unequal subunits with a combined molecular weight of approximately 4 million Daltons and contain 70-80 different protein molecules and four different RNAs. Currently the only structural information on eukaryotic ribosomes is available from cryo electron microscopic reconstructions in the nanometer resolution range, which is insufficient to derive information about the function of the eukaryotic ribosome at the atomic level. The aim of this proposal is to use X-ray crystallography to obtain structural and functional information on the eukaryotic ribosome and its functional complexes at high resolution. The key targets of the structural work will be: i) the structure of the small ribosomal subunit, ii) the structure of the large ribosomal subunit, and iii) structures of complexes involved in the initiation of protein synthesis. Besides the obvious fundamental importance of this research for understanding protein synthesis in eukaryotes the proposed studies will also be the prerequisite for understanding the structural basis of the regulation of protein synthesis in normal cells and how it is perturbed in various diseases. Finally, comparing the structures of bacterial and eukaryotic ribosomes is important for understanding the specificity of various clinically used antibiotics for the bacterial ribosome.
Max ERC Funding
2 446 725 €
Duration
Start date: 2010-07-01, End date: 2015-06-30
Project acronym FLAMENANOMANUFACTURE
Project Flame Aerosol Reactors for Manufacturing of Surface-Functionalized Nanoscale Materials and Devices
Researcher (PI) Sotirios Pratsinis
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE8, ERC-2009-AdG
Summary Nanotechnology research has been directed mostly to the design and synthesis of (a) materials with passive nanostructures (e.g. coatings, nanoparticles of organics, metals and ceramics) and (b) active devices with nanostructured materials (e.g. transistors, amplifiers, sensors, actuators etc). Little is known, however, about how well the unique properties of nanostructured materials are reproduced during their large scale synthesis, and how such manufacturing can be designed and carried out. A key goal here is to fundamentally understand synthesis of surface-functionalized, nanostructured, multicomponent particles by flame aerosol reactors (a proven scalable technology for simple ceramic oxide nanopowders). That way technology for making such sophisticated materials would be developed systematically for their efficient manufacture so that active devices containing them can be made economically. Our focus is on understanding aerosol formation of layered solid or fractal-like nanostructures by developing quantitative process models and systematic comparison to experimental data. This understanding will be used to guide synthesis of challenging nanoparticle compositions and process scale-up with close attention to safe product handling and health effects. The ultimate goal of this research is to address the next frontier of this field, namely the assembling of high performance active devices made with such functionalized or layered nanoparticles. Here these devices include but not limited to (a) actuators containing layered single superparamagnetic nanoparticles and (b) ultraselective and highly sensitive sensors made with highly conductive but disperse nanoelectrode layers for detection of trace organic vapors in the human breath for early diagnosis of serious illnesses.
Summary
Nanotechnology research has been directed mostly to the design and synthesis of (a) materials with passive nanostructures (e.g. coatings, nanoparticles of organics, metals and ceramics) and (b) active devices with nanostructured materials (e.g. transistors, amplifiers, sensors, actuators etc). Little is known, however, about how well the unique properties of nanostructured materials are reproduced during their large scale synthesis, and how such manufacturing can be designed and carried out. A key goal here is to fundamentally understand synthesis of surface-functionalized, nanostructured, multicomponent particles by flame aerosol reactors (a proven scalable technology for simple ceramic oxide nanopowders). That way technology for making such sophisticated materials would be developed systematically for their efficient manufacture so that active devices containing them can be made economically. Our focus is on understanding aerosol formation of layered solid or fractal-like nanostructures by developing quantitative process models and systematic comparison to experimental data. This understanding will be used to guide synthesis of challenging nanoparticle compositions and process scale-up with close attention to safe product handling and health effects. The ultimate goal of this research is to address the next frontier of this field, namely the assembling of high performance active devices made with such functionalized or layered nanoparticles. Here these devices include but not limited to (a) actuators containing layered single superparamagnetic nanoparticles and (b) ultraselective and highly sensitive sensors made with highly conductive but disperse nanoelectrode layers for detection of trace organic vapors in the human breath for early diagnosis of serious illnesses.
Max ERC Funding
2 500 000 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
