Project acronym AEROSPACEPHYS
Project Multiphysics models and simulations for reacting and plasma flows applied to the space exploration program
Researcher (PI) Thierry Edouard Bertrand Magin
Host Institution (HI) INSTITUT VON KARMAN DE DYNAMIQUE DES FLUIDES
Call Details Starting Grant (StG), PE8, ERC-2010-StG_20091028
Summary Space exploration is one of boldest and most exciting endeavors that humanity has undertaken, and it holds enormous promise for the future. Our next challenges for the spatial conquest include bringing back samples to Earth by means of robotic missions and continuing the manned exploration program, which aims at sending human beings to Mars and bring them home safely. Inaccurate prediction of the heat-flux to the surface of the spacecraft heat shield can be fatal for the crew or the success of a robotic mission. This quantity is estimated during the design phase. An accurate prediction is a particularly complex task, regarding modelling of the following phenomena that are potential “mission killers:” 1) Radiation of the plasma in the shock layer, 2) Complex surface chemistry on the thermal protection material, 3) Flow transition from laminar to turbulent. Our poor understanding of the coupled mechanisms of radiation, ablation, and transition leads to the difficulties in flux prediction. To avoid failure and ensure safety of the astronauts and payload, engineers resort to “safety factors” to determine the thickness of the heat shield, at the expense of the mass of embarked payload. Thinking out of the box and basic research are thus necessary for advancements of the models that will better define the environment and requirements for the design and safe operation of tomorrow’s space vehicles and planetary probes for the manned space exploration. The three basic ingredients for predictive science are: 1) Physico-chemical models, 2) Computational methods, 3) Experimental data. We propose to follow a complementary approach for prediction. The proposed research aims at: “Integrating new advanced physico-chemical models and computational methods, based on a multidisciplinary approach developed together with physicists, chemists, and applied mathematicians, to create a top-notch multiphysics and multiscale numerical platform for simulations of planetary atmosphere entries, crucial to the new challenges of the manned space exploration program. Experimental data will also be used for validation, following state-of-the-art uncertainty quantification methods.”
Summary
Space exploration is one of boldest and most exciting endeavors that humanity has undertaken, and it holds enormous promise for the future. Our next challenges for the spatial conquest include bringing back samples to Earth by means of robotic missions and continuing the manned exploration program, which aims at sending human beings to Mars and bring them home safely. Inaccurate prediction of the heat-flux to the surface of the spacecraft heat shield can be fatal for the crew or the success of a robotic mission. This quantity is estimated during the design phase. An accurate prediction is a particularly complex task, regarding modelling of the following phenomena that are potential “mission killers:” 1) Radiation of the plasma in the shock layer, 2) Complex surface chemistry on the thermal protection material, 3) Flow transition from laminar to turbulent. Our poor understanding of the coupled mechanisms of radiation, ablation, and transition leads to the difficulties in flux prediction. To avoid failure and ensure safety of the astronauts and payload, engineers resort to “safety factors” to determine the thickness of the heat shield, at the expense of the mass of embarked payload. Thinking out of the box and basic research are thus necessary for advancements of the models that will better define the environment and requirements for the design and safe operation of tomorrow’s space vehicles and planetary probes for the manned space exploration. The three basic ingredients for predictive science are: 1) Physico-chemical models, 2) Computational methods, 3) Experimental data. We propose to follow a complementary approach for prediction. The proposed research aims at: “Integrating new advanced physico-chemical models and computational methods, based on a multidisciplinary approach developed together with physicists, chemists, and applied mathematicians, to create a top-notch multiphysics and multiscale numerical platform for simulations of planetary atmosphere entries, crucial to the new challenges of the manned space exploration program. Experimental data will also be used for validation, following state-of-the-art uncertainty quantification methods.”
Max ERC Funding
1 494 892 €
Duration
Start date: 2010-09-01, End date: 2015-08-31
Project acronym BRAINSHAPE
Project Objects in sight: the neural basis of visuomotor transformations for actions towards objects
Researcher (PI) Peter Anna J Janssen
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary Humans and other primates possess an exquisite capacity to grasp and manipulate objects. The seemingly effortless interaction with objects in everyday life is subserved by a number of cortical areas of the visual and the motor system. Recent research has highlighted that dorsal stream areas in the posterior parietal cortex are involved in object processing. Because parietal lesions do not impair object recognition, the encoding of object shape in posterior parietal cortex is considered to be important for the planning of actions towards objects. In order to succesfully grasp an object, the complex pattern of visual information impinging on the retina has to be transformed into a motor plan that can control the muscle contractions. The neural basis of visuomotor transformations necessary for directing actions towards objects, however, has remained largely unknown. This proposal aims to unravel the pathways and mechanisms involved in programming actions towards objects - an essential capacity for our very survival. We envision an integrated approach to study the transformation of visual information into motor commands in the macaque brain, combining functional imaging, single-cell recording, microstimulation and reversible inactivation. Our research efforts will be focussed on parietal area AIP and premotor area F5, two key brain areas for visually-guided grasping. Above all, this proposal will move beyond purely descriptive measurements of neural activity by implementing manipulations of brain activity to reveal behavioral effects and interdependencies of cortical areas. Finally the data obtained in this project will pave the way to use the neural activity recorded in visuomotor areas to act upon the environment by grasping objects by means of a robot hand.
Summary
Humans and other primates possess an exquisite capacity to grasp and manipulate objects. The seemingly effortless interaction with objects in everyday life is subserved by a number of cortical areas of the visual and the motor system. Recent research has highlighted that dorsal stream areas in the posterior parietal cortex are involved in object processing. Because parietal lesions do not impair object recognition, the encoding of object shape in posterior parietal cortex is considered to be important for the planning of actions towards objects. In order to succesfully grasp an object, the complex pattern of visual information impinging on the retina has to be transformed into a motor plan that can control the muscle contractions. The neural basis of visuomotor transformations necessary for directing actions towards objects, however, has remained largely unknown. This proposal aims to unravel the pathways and mechanisms involved in programming actions towards objects - an essential capacity for our very survival. We envision an integrated approach to study the transformation of visual information into motor commands in the macaque brain, combining functional imaging, single-cell recording, microstimulation and reversible inactivation. Our research efforts will be focussed on parietal area AIP and premotor area F5, two key brain areas for visually-guided grasping. Above all, this proposal will move beyond purely descriptive measurements of neural activity by implementing manipulations of brain activity to reveal behavioral effects and interdependencies of cortical areas. Finally the data obtained in this project will pave the way to use the neural activity recorded in visuomotor areas to act upon the environment by grasping objects by means of a robot hand.
Max ERC Funding
1 499 200 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym CAT4ENSUS
Project Molecular Catalysts Made of Earth-Abundant Elements for Energy and Sustainability
Researcher (PI) Xile Hu
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), PE5, ERC-2010-StG_20091028
Summary Energy and sustainability are among the biggest challenges humanity faces this century. Catalysis is an indispensable component for many potential solutions, and fundamental research in catalysis is as urgent as ever. Here, we propose to build up an interdisciplinary research program in molecular catalysis to address the challenges of energy and sustainability. There are two specific aims: (I) bio-inspired sulfur-rich metal complexes as efficient and practical electrocatalysts for hydrogen production and CO2 reduction; (II) well-defined Fe complexes of chelating pincer ligands for chemo- and stereoselective organic synthesis. An important feature of the proposed catalysts is that they are made of earth-abundant and readily available elements such as Fe, Co, Ni, S, N, etc.
Design and synthesis of catalysts are the starting point and a key aspect of this project. A major inspiration comes from nature, where metallo-enzymes use readily available metals for fuel production and challenging reactions. Our accumulated knowledge and experience in spectroscopy, electrochemistry, reaction chemistry, mechanism, and catalysis will enable us to thoroughly study the synthetic catalysts and their applications towards the research targets. Furthermore, we will explore research territories such as electrode modification and fabrication, catalyst immobilization and attachment, and asymmetric catalysis.
The proposed research should not only result in new insights and knowledge in catalysis that are relevant to energy and sustainability, but also produce functional, scalable, and economically feasible catalysts for fuel production and organic synthesis. The program can contribute to excellence in European research.
Summary
Energy and sustainability are among the biggest challenges humanity faces this century. Catalysis is an indispensable component for many potential solutions, and fundamental research in catalysis is as urgent as ever. Here, we propose to build up an interdisciplinary research program in molecular catalysis to address the challenges of energy and sustainability. There are two specific aims: (I) bio-inspired sulfur-rich metal complexes as efficient and practical electrocatalysts for hydrogen production and CO2 reduction; (II) well-defined Fe complexes of chelating pincer ligands for chemo- and stereoselective organic synthesis. An important feature of the proposed catalysts is that they are made of earth-abundant and readily available elements such as Fe, Co, Ni, S, N, etc.
Design and synthesis of catalysts are the starting point and a key aspect of this project. A major inspiration comes from nature, where metallo-enzymes use readily available metals for fuel production and challenging reactions. Our accumulated knowledge and experience in spectroscopy, electrochemistry, reaction chemistry, mechanism, and catalysis will enable us to thoroughly study the synthetic catalysts and their applications towards the research targets. Furthermore, we will explore research territories such as electrode modification and fabrication, catalyst immobilization and attachment, and asymmetric catalysis.
The proposed research should not only result in new insights and knowledge in catalysis that are relevant to energy and sustainability, but also produce functional, scalable, and economically feasible catalysts for fuel production and organic synthesis. The program can contribute to excellence in European research.
Max ERC Funding
1 475 712 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym CELLTYPESANDCIRCUITS
Project Neural circuit function in the retina of mice and humans
Researcher (PI) Botond Roska
Host Institution (HI) FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary The mammalian brain is assembled from thousands of neuronal cell types that are organized into distinct circuits to perform behaviourally relevant computations. To gain mechanistic insights about brain function and to treat specific diseases of the nervous system it is crucial to understand what these local circuits are computing and how they achieve these computations. By examining the structure and function of a few genetically identified and experimentally accessible neural circuits we plan to address fundamental questions about the functional architecture of neural circuits. First, are cell types assigned to a unique functional circuit with a well-defined function or do they participate in multiple circuits (multitasking cell types), adjusting their role depending on the state of these circuits? Second, does a neural circuit perform a single computation or depending on the information content of its inputs can it carry out radically different functions? Third, how, among the large number of other cell types, do the cells belonging to the same functional circuit connect together during development? We use the mouse retina as a model system to address these questions. Finally, we will study the structure and function of a specialised neural circuit in the human fovea that enables humans to read. We predict that our insights into the mechanism of multitasking, network switches and the development of selective connectivity will be instructive to study similar phenomena in other brain circuits. Knowledge of the structure and function of the human fovea will open up new opportunities to correlate human retinal function with human visual behaviour and our genetic technologies to study human foveal function will allow us and others to design better strategies for restoring vision for the blind.
Summary
The mammalian brain is assembled from thousands of neuronal cell types that are organized into distinct circuits to perform behaviourally relevant computations. To gain mechanistic insights about brain function and to treat specific diseases of the nervous system it is crucial to understand what these local circuits are computing and how they achieve these computations. By examining the structure and function of a few genetically identified and experimentally accessible neural circuits we plan to address fundamental questions about the functional architecture of neural circuits. First, are cell types assigned to a unique functional circuit with a well-defined function or do they participate in multiple circuits (multitasking cell types), adjusting their role depending on the state of these circuits? Second, does a neural circuit perform a single computation or depending on the information content of its inputs can it carry out radically different functions? Third, how, among the large number of other cell types, do the cells belonging to the same functional circuit connect together during development? We use the mouse retina as a model system to address these questions. Finally, we will study the structure and function of a specialised neural circuit in the human fovea that enables humans to read. We predict that our insights into the mechanism of multitasking, network switches and the development of selective connectivity will be instructive to study similar phenomena in other brain circuits. Knowledge of the structure and function of the human fovea will open up new opportunities to correlate human retinal function with human visual behaviour and our genetic technologies to study human foveal function will allow us and others to design better strategies for restoring vision for the blind.
Max ERC Funding
1 499 000 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym COMPUSLANG
Project Neural and computational determinants of left cerebral dominance in speech and language
Researcher (PI) Anne-Lise Mamessier
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary More than a century after Wernicke and Broca established that speech perception and production rely on temporal and prefrontal cortices of the left brain hemisphere, the biological determinants for this organization are still unknown. While functional neuroanatomy has been described in great detail, the neuroscience of language still lacks a physiologically plausible model of the neuro-computational mechanisms for coding and decoding of speech acoustic signal. We propose to fill this gap by testing the biological validity and exploring the computational implications of one promising proposal, the Asymmetric Sampling in Time theory. AST assumes that speech signals are analysed in parallel at multiple timescales and that these timescales differ between left and right cerebral hemispheres. This theory is original and provocative as it implies that a single computational difference, distinct integration windows in right and left auditory cortices could be sufficient to explain why speech is preferentially processed by the left brain, and possible even why the human brain has evolved toward such an asymmetric functional organization. Our proposal has four goals: 1/ to validate, invalidate or amend AST on the basis of physiological experiments in healthy human subjects including functional magnetic resonance imaging (fMRI), combined electroencephalography (EEG) and fMRI, magnetoencephalography (MEG) and subdural electrocorticography (EcoG), 2/ to use computational modeling to probe those aspects of the theory that currently remain inaccessible to empirical testing (evaluation, assessment), 3/ to apply AST to binaural artificial hearing with cochlear implants, 4/ to test for disorders of auditory sampling in autism and dyslexia, two language neurodevelopmental pathologies in which a genetic basis implicates the physiological underpinnings of AST, and 5/ to assess potential generalisation of AST to linguistic action in the context of speech production.
Summary
More than a century after Wernicke and Broca established that speech perception and production rely on temporal and prefrontal cortices of the left brain hemisphere, the biological determinants for this organization are still unknown. While functional neuroanatomy has been described in great detail, the neuroscience of language still lacks a physiologically plausible model of the neuro-computational mechanisms for coding and decoding of speech acoustic signal. We propose to fill this gap by testing the biological validity and exploring the computational implications of one promising proposal, the Asymmetric Sampling in Time theory. AST assumes that speech signals are analysed in parallel at multiple timescales and that these timescales differ between left and right cerebral hemispheres. This theory is original and provocative as it implies that a single computational difference, distinct integration windows in right and left auditory cortices could be sufficient to explain why speech is preferentially processed by the left brain, and possible even why the human brain has evolved toward such an asymmetric functional organization. Our proposal has four goals: 1/ to validate, invalidate or amend AST on the basis of physiological experiments in healthy human subjects including functional magnetic resonance imaging (fMRI), combined electroencephalography (EEG) and fMRI, magnetoencephalography (MEG) and subdural electrocorticography (EcoG), 2/ to use computational modeling to probe those aspects of the theory that currently remain inaccessible to empirical testing (evaluation, assessment), 3/ to apply AST to binaural artificial hearing with cochlear implants, 4/ to test for disorders of auditory sampling in autism and dyslexia, two language neurodevelopmental pathologies in which a genetic basis implicates the physiological underpinnings of AST, and 5/ to assess potential generalisation of AST to linguistic action in the context of speech production.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-02-01, End date: 2016-01-31
Project acronym DECCAPAC
Project Design and Exploitation of C-C and C-H Activation Pathways in Asymmetric Catalysis
Researcher (PI) Nicolai Cramer
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), PE5, ERC-2010-StG_20091028
Summary Synthesizing organic molecules in high purity with designed properties is of utmost importance for pharmaceutical applications and material- and polymer sciences including the efficient production of enantiopure compounds and the compliance with ecological concerns and sustainability. The efficiency of all reaction classes has improved over the past decades. However, the basic principle and execution did not change: The target molecule is disconnected into donor and acceptor synthons and appropriate functional groups need to be introduced and adjusted to carry out the envisioned coupling. These additional steps decrease the yield and efficiency, are costly in time, resources and produce waste. The introduction of new functionalities by direct C-H or C-C bond activation is a unique and highly appealing strategy. The range of substrates is virtually unlimited, including hydrocarbons, small molecules and polymers. Such dream reactions avoid any pre-functionalization, shorten synthetic routes, make unsought disconnections possible and allow for a more efficient usage of our dwindling resources. Despite recent progress in the activations of inert bonds, narrow scopes, poor reactivities and harsh conditions hamper most general practical applications. Especially, enantioselective activations are a longstanding challenge. The outlined project seeks to address these issues by the development and exploitation of new catalytic enantioselective C-H and C-C functionalizations of broadly available organic substrates, using chiral Rh- and Pd- catalysts, additionally supported by automated screening and computational techniques. These reactions will be then applied in the streamlined synthesis of pharmaceutically relevant scaffolds and of compounds for organic electronics.
Summary
Synthesizing organic molecules in high purity with designed properties is of utmost importance for pharmaceutical applications and material- and polymer sciences including the efficient production of enantiopure compounds and the compliance with ecological concerns and sustainability. The efficiency of all reaction classes has improved over the past decades. However, the basic principle and execution did not change: The target molecule is disconnected into donor and acceptor synthons and appropriate functional groups need to be introduced and adjusted to carry out the envisioned coupling. These additional steps decrease the yield and efficiency, are costly in time, resources and produce waste. The introduction of new functionalities by direct C-H or C-C bond activation is a unique and highly appealing strategy. The range of substrates is virtually unlimited, including hydrocarbons, small molecules and polymers. Such dream reactions avoid any pre-functionalization, shorten synthetic routes, make unsought disconnections possible and allow for a more efficient usage of our dwindling resources. Despite recent progress in the activations of inert bonds, narrow scopes, poor reactivities and harsh conditions hamper most general practical applications. Especially, enantioselective activations are a longstanding challenge. The outlined project seeks to address these issues by the development and exploitation of new catalytic enantioselective C-H and C-C functionalizations of broadly available organic substrates, using chiral Rh- and Pd- catalysts, additionally supported by automated screening and computational techniques. These reactions will be then applied in the streamlined synthesis of pharmaceutically relevant scaffolds and of compounds for organic electronics.
Max ERC Funding
1 499 500 €
Duration
Start date: 2011-02-01, End date: 2016-01-31
Project acronym FUBSSY
Project Functional Biosupramolecular Systems: Photosystems and Sensors
Researcher (PI) Stefan Georg Jean-Petit-Matile
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Advanced Grant (AdG), PE5, ERC-2010-AdG_20100224
Summary The general objective of this proposal is to discover access to ordered, soft and smart matter for use in materials sciences (e.g. molecular optoelectronics, organic solar cells), biology, medicine and chemistry.
Specific aim 1 focuses on two complementary approaches (zipper assembly; self-organizing surface-initiated polymerization, SOSIP) to build artificial photosystems on solid surfaces, including supramolecular n/p-heterojunctions with oriented multicolor antiparallel redox gradients (“OMARG-SHJs”).
Specific aim 2 is to create sensing systems in lipid bilayers that operate by pattern recognition with polyion/counterion complexes, and to apply the lessons learned to several interconnected topics (diagnostics, fluorescent membrane/nitrate probes, cellular uptake, organocatalysis with anion-À interactions).
To address these challenges, crossfertilization at the interface of synthetic, supramolecular, biological and materials chemistry will be essential. To produce the broad horizons needed for crossfertilization, projects on different topics are run in parallel. The proposed approach builds in general on the distinguishing expertise of the (organic) chemist to create new matter, i.e., multistep organic synthesis. To identify significant, that is responsive or “smart” systems, the invention of functional feedback loops will be emphasized.
Success with aim 1 will provide general solutions to key problems (OMARG-SHJs, SOSIP) and thus lead to broad applications (including high-efficiency organic photovoltaics and dye-sensitized solar cells). Success with aim 2 will afford synthetic sensing systems that operate, closer than ever, like the membrane-based mammalian olfactory and gustatory systems and open new approaches to crossdisciplinary topics as specified above.
Summary
The general objective of this proposal is to discover access to ordered, soft and smart matter for use in materials sciences (e.g. molecular optoelectronics, organic solar cells), biology, medicine and chemistry.
Specific aim 1 focuses on two complementary approaches (zipper assembly; self-organizing surface-initiated polymerization, SOSIP) to build artificial photosystems on solid surfaces, including supramolecular n/p-heterojunctions with oriented multicolor antiparallel redox gradients (“OMARG-SHJs”).
Specific aim 2 is to create sensing systems in lipid bilayers that operate by pattern recognition with polyion/counterion complexes, and to apply the lessons learned to several interconnected topics (diagnostics, fluorescent membrane/nitrate probes, cellular uptake, organocatalysis with anion-À interactions).
To address these challenges, crossfertilization at the interface of synthetic, supramolecular, biological and materials chemistry will be essential. To produce the broad horizons needed for crossfertilization, projects on different topics are run in parallel. The proposed approach builds in general on the distinguishing expertise of the (organic) chemist to create new matter, i.e., multistep organic synthesis. To identify significant, that is responsive or “smart” systems, the invention of functional feedback loops will be emphasized.
Success with aim 1 will provide general solutions to key problems (OMARG-SHJs, SOSIP) and thus lead to broad applications (including high-efficiency organic photovoltaics and dye-sensitized solar cells). Success with aim 2 will afford synthetic sensing systems that operate, closer than ever, like the membrane-based mammalian olfactory and gustatory systems and open new approaches to crossdisciplinary topics as specified above.
Max ERC Funding
1 906 200 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym LILO
Project Light-In, Light-Out: Chemistry for sustainable energy technologies
Researcher (PI) Edwin Charles Constable
Host Institution (HI) UNIVERSITAT BASEL
Call Details Advanced Grant (AdG), PE5, ERC-2010-AdG_20100224
Summary The project is concerned with a coordinated approach to the development of of novel chemical strategies for light harvesting by photovoltaic cells and light generation using light emitting electrochemical cells. Both technologies have proof of principle results from the PIs own laboratory and others world-wide. The bulk of efficient dye sensitized solar cells rely on transition metal complexes as the photoactive component as the majority of traditional organic dyes do not possess long term stability under the operating conditions of the devices. LECs based upon transition metal complexes have been shown to possess lifetimes sufficiently long and efficiencies sufficiently high to become a viable alternative technology to OLEDs in the near future. The disadvantages of state of the art devices for both technologies is that they are based upon second or third row transition metal complexes. Although these elements are expensive, the principle difficulties arise from their low abundance, which creates significant issues of sustainability if the technology is to be adopted. The aim of this project is three-fold. Firstly, to further optimise the individual technologies using conventional transition metal complexes, with increases in efficiency leading to lower metal requirements. Secondly, to explore the periodic table for metal-containing luminophores based on first row transition metals, with an emphasis upon copper and zinc containing species. The final aspect is related to the utilization of solar derived electrons for water splitting reactions, allowing the generation of hydrogen and/or reaction products of hydrogen with organic species. This latter aspect is related to the mid-term requirement for liquid fuels, regardless of the primary fuel sources utilized. The program will involve design and synthesis of new materials, device construction and evaluation (in-house and with existing academic and industrial partners) and iterative refinement of structures
Summary
The project is concerned with a coordinated approach to the development of of novel chemical strategies for light harvesting by photovoltaic cells and light generation using light emitting electrochemical cells. Both technologies have proof of principle results from the PIs own laboratory and others world-wide. The bulk of efficient dye sensitized solar cells rely on transition metal complexes as the photoactive component as the majority of traditional organic dyes do not possess long term stability under the operating conditions of the devices. LECs based upon transition metal complexes have been shown to possess lifetimes sufficiently long and efficiencies sufficiently high to become a viable alternative technology to OLEDs in the near future. The disadvantages of state of the art devices for both technologies is that they are based upon second or third row transition metal complexes. Although these elements are expensive, the principle difficulties arise from their low abundance, which creates significant issues of sustainability if the technology is to be adopted. The aim of this project is three-fold. Firstly, to further optimise the individual technologies using conventional transition metal complexes, with increases in efficiency leading to lower metal requirements. Secondly, to explore the periodic table for metal-containing luminophores based on first row transition metals, with an emphasis upon copper and zinc containing species. The final aspect is related to the utilization of solar derived electrons for water splitting reactions, allowing the generation of hydrogen and/or reaction products of hydrogen with organic species. This latter aspect is related to the mid-term requirement for liquid fuels, regardless of the primary fuel sources utilized. The program will involve design and synthesis of new materials, device construction and evaluation (in-house and with existing academic and industrial partners) and iterative refinement of structures
Max ERC Funding
2 399 440 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym MIRNA
Project Metal Ions and Metal Ion Complexes Guiding Folding and Function of Single RNA Molecules
Researcher (PI) Roland Karl Oliver Sigel
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Starting Grant (StG), PE5, ERC-2010-StG_20091028
Summary RNAs play crucial roles in cellular metabolic processes, e.g. ribozymes in RNA-processing or riboswitches in the regulation of protein expression. Metal ions thereby guide and determine folding and function of every complex nucleic acid structure. Recently, it has become increasingly evident that RNA folding and catalysis are extremely sensitive to changes in concentration and nature of the metal ion involved as well as to single-atom changes in metal ion complexes. The elucidation of the specific binding of certain metal ions and their complexes by nucleic acids poses an enormous challenge. This recognition process must depend solely on basic coordination chemical principles but is poorly understood. The goal of this project is to understand the effect of metal ions and their complexes on local and global structure formation of single large RNAs: Specifically, the influence of metal ions on the assembly of the catalytic core of group II intron ribozymes as well as the influence of single corrin side chains of coenzyme B12 to induce the structural change of its 202 nucleotide long riboswitch will be characterized. Combining classical Inorganic, Coordination, Analytical, and Organic Chemistry with Biophysics, we will apply single molecule Förster Resonance Energy Transfer spectroscopy (smFRET) together with hydrolytic cleavage experiments and chemical synthesis. SmFRET studies allow us to investigate every molecule individually instead of a bulk signal and thus to observe also minor populations. Our results will reveal how single metal ions and ligand atoms guide and influence global structure, folding, and function of ribozymes and riboswitches, and promise to have a significant impact on Biological Inorganic Chemistry, RNA Biochemistry, as well as Medicinal Chemistry.
Summary
RNAs play crucial roles in cellular metabolic processes, e.g. ribozymes in RNA-processing or riboswitches in the regulation of protein expression. Metal ions thereby guide and determine folding and function of every complex nucleic acid structure. Recently, it has become increasingly evident that RNA folding and catalysis are extremely sensitive to changes in concentration and nature of the metal ion involved as well as to single-atom changes in metal ion complexes. The elucidation of the specific binding of certain metal ions and their complexes by nucleic acids poses an enormous challenge. This recognition process must depend solely on basic coordination chemical principles but is poorly understood. The goal of this project is to understand the effect of metal ions and their complexes on local and global structure formation of single large RNAs: Specifically, the influence of metal ions on the assembly of the catalytic core of group II intron ribozymes as well as the influence of single corrin side chains of coenzyme B12 to induce the structural change of its 202 nucleotide long riboswitch will be characterized. Combining classical Inorganic, Coordination, Analytical, and Organic Chemistry with Biophysics, we will apply single molecule Förster Resonance Energy Transfer spectroscopy (smFRET) together with hydrolytic cleavage experiments and chemical synthesis. SmFRET studies allow us to investigate every molecule individually instead of a bulk signal and thus to observe also minor populations. Our results will reveal how single metal ions and ligand atoms guide and influence global structure, folding, and function of ribozymes and riboswitches, and promise to have a significant impact on Biological Inorganic Chemistry, RNA Biochemistry, as well as Medicinal Chemistry.
Max ERC Funding
1 495 729 €
Duration
Start date: 2010-12-01, End date: 2015-11-30
Project acronym MIRNA_AD
Project Role of microRNA dysregulation in Alzheimers Disease
Researcher (PI) Bart Geert Alfons Paul De Strooper
Host Institution (HI) VIB
Call Details Advanced Grant (AdG), LS5, ERC-2010-AdG_20100317
Summary Alzheimer's Disease (AD) is a major health problem in aging societies. Remarkable progress in the study of the rare genetic forms of the disease has lead to the identification of several key players like APP and the secretases, but the molecular basis of sporadic AD remains largely unresolved. The convergence of several factors (multicausality) has to be considered. miRNAs are crucially involved in normal brain functioning and integrity. Evidence obtained from analyzing a limited number of brains indicates that miRNA expression is affected in sporadic AD. We propose the hypothesis that such changes can affect normal functioning of neurons increasing their susceptibility to AD. We will document in 3 brain regions in >100 sporadic AD patients and in >100 controls alterations in miRNA expression and explore whether similar alterations can be detected in cerebrospinal fluid. This part of the study will firmly establish which miRNAs are altered in AD. We will then investigate the functional relevance of those miRNAs by gain and loss of function experiments in brains of zebra fish and mice. We will determine the target genes of the miRNA with genetic and proteomic approaches, and establish the functional networks controlled by those miRNA. We anticipate that this will lead to complete novel insights in the role of miRNAs in AD and in maintenance of brain integrity. Our work is likely to have diagnostic relevance for AD and will identify novel drug targets for the disease.
Summary
Alzheimer's Disease (AD) is a major health problem in aging societies. Remarkable progress in the study of the rare genetic forms of the disease has lead to the identification of several key players like APP and the secretases, but the molecular basis of sporadic AD remains largely unresolved. The convergence of several factors (multicausality) has to be considered. miRNAs are crucially involved in normal brain functioning and integrity. Evidence obtained from analyzing a limited number of brains indicates that miRNA expression is affected in sporadic AD. We propose the hypothesis that such changes can affect normal functioning of neurons increasing their susceptibility to AD. We will document in 3 brain regions in >100 sporadic AD patients and in >100 controls alterations in miRNA expression and explore whether similar alterations can be detected in cerebrospinal fluid. This part of the study will firmly establish which miRNAs are altered in AD. We will then investigate the functional relevance of those miRNAs by gain and loss of function experiments in brains of zebra fish and mice. We will determine the target genes of the miRNA with genetic and proteomic approaches, and establish the functional networks controlled by those miRNA. We anticipate that this will lead to complete novel insights in the role of miRNAs in AD and in maintenance of brain integrity. Our work is likely to have diagnostic relevance for AD and will identify novel drug targets for the disease.
Max ERC Funding
2 500 000 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
