Project acronym AXONGROWTH
Project Systematic analysis of the molecular mechanisms underlying axon growth during development and following injury
Researcher (PI) Oren Schuldiner
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary Axon growth potential declines during development, contributing to the lack of effective regeneration in the adult central nervous system. What determines the intrinsic growth potential of neurites, and how such growth is regulated during development, disease and following injury is a fundamental question in neuroscience. Although multiple lines of evidence indicate that intrinsic growth capability is genetically encoded, its nature remains poorly defined. Neuronal remodeling of the Drosophila mushroom body offers a unique opportunity to study the mechanisms of various types of axon degeneration and growth. We have recently demonstrated that regrowth of axons following developmental pruning is not only distinct from initial outgrowth but also shares molecular similarities with regeneration following injury. In this proposal we combine state of the art tools from genomics, functional genetics and microscopy to perform a comprehensive study of the mechanisms underlying axon growth during development and following injury. First, we will combine genetic, biochemical and genomic studies to gain a mechanistic understanding of the developmental regrowth program. Next, we will perform extensive transcriptomic analyses and comparisons aimed at defining the genetic programs involved in initial axon growth, developmental regrowth, and regeneration following injury. Finally, we will harness the genetic power of Drosophila to perform a comprehensive functional analysis of genes and pathways, those previously known and new ones that we will discover, in various neurite growth paradigms. Importantly, these functional assays will be performed in the same organism, allowing us to use identical genetic mutations across our analyses. To this end, our identification of a new genetic program regulating developmental axon regrowth, together with emerging tools in genomics, places us in a unique position to gain a broad understanding of axon growth during development and following injury.
Summary
Axon growth potential declines during development, contributing to the lack of effective regeneration in the adult central nervous system. What determines the intrinsic growth potential of neurites, and how such growth is regulated during development, disease and following injury is a fundamental question in neuroscience. Although multiple lines of evidence indicate that intrinsic growth capability is genetically encoded, its nature remains poorly defined. Neuronal remodeling of the Drosophila mushroom body offers a unique opportunity to study the mechanisms of various types of axon degeneration and growth. We have recently demonstrated that regrowth of axons following developmental pruning is not only distinct from initial outgrowth but also shares molecular similarities with regeneration following injury. In this proposal we combine state of the art tools from genomics, functional genetics and microscopy to perform a comprehensive study of the mechanisms underlying axon growth during development and following injury. First, we will combine genetic, biochemical and genomic studies to gain a mechanistic understanding of the developmental regrowth program. Next, we will perform extensive transcriptomic analyses and comparisons aimed at defining the genetic programs involved in initial axon growth, developmental regrowth, and regeneration following injury. Finally, we will harness the genetic power of Drosophila to perform a comprehensive functional analysis of genes and pathways, those previously known and new ones that we will discover, in various neurite growth paradigms. Importantly, these functional assays will be performed in the same organism, allowing us to use identical genetic mutations across our analyses. To this end, our identification of a new genetic program regulating developmental axon regrowth, together with emerging tools in genomics, places us in a unique position to gain a broad understanding of axon growth during development and following injury.
Max ERC Funding
2 000 000 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym CANALOHMICS
Project Biophysical networks underlying the robustness of neuronal excitability
Researcher (PI) Jean-Marc Goaillard
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary The mammalian nervous system is in some respect surprisingly robust to perturbations, as suggested by the virtually complete recovery of brain function after strokes or the pre-clinical asymptomatic phase of Parkinson’s disease. Ultimately though, cognitive and behavioral robustness relies on the ability of single neurons to cope with perturbations, and in particular to maintain a constant and reliable transfer of information.
So far, the main facet of robustness that has been studied at the neuronal level is homeostatic plasticity of electrical activity, which refers to the ability of neurons to stabilize their activity level in response to external perturbations. But neurons are also able to maintain their function when one of the major ion channels underlying their activity is deleted or mutated: the number of ion channel subtypes expressed by most excitable cells by far exceeds the minimal number of components necessary to achieve function, offering great potential for compensation when one of the channel’s function is altered. How ion channels are dynamically co-regulated to maintain the appropriate pattern of activity has yet to be determined.
In the current project, we will develop a systems-level approach to robustness of neuronal activity based on the combination of electrophysiology, microfluidic single-cell qPCR and computational modeling. We propose to i) characterize the electrical phenotype of dopaminergic neurons following different types of perturbations (ion channel KO, chronic pharmacological treatment), ii) measure the quantitatives changes in ion channel transcriptome (40 voltage-dependent ion channels) associated with these perturbations and iii) determine the mathematical relationships between quantitative changes in ion channel expression and electrical phenotype. Although focused on dopaminergic neurons, this project will provide a general framework that could be applied to any type of excitable cell to decipher its code of robustness.
Summary
The mammalian nervous system is in some respect surprisingly robust to perturbations, as suggested by the virtually complete recovery of brain function after strokes or the pre-clinical asymptomatic phase of Parkinson’s disease. Ultimately though, cognitive and behavioral robustness relies on the ability of single neurons to cope with perturbations, and in particular to maintain a constant and reliable transfer of information.
So far, the main facet of robustness that has been studied at the neuronal level is homeostatic plasticity of electrical activity, which refers to the ability of neurons to stabilize their activity level in response to external perturbations. But neurons are also able to maintain their function when one of the major ion channels underlying their activity is deleted or mutated: the number of ion channel subtypes expressed by most excitable cells by far exceeds the minimal number of components necessary to achieve function, offering great potential for compensation when one of the channel’s function is altered. How ion channels are dynamically co-regulated to maintain the appropriate pattern of activity has yet to be determined.
In the current project, we will develop a systems-level approach to robustness of neuronal activity based on the combination of electrophysiology, microfluidic single-cell qPCR and computational modeling. We propose to i) characterize the electrical phenotype of dopaminergic neurons following different types of perturbations (ion channel KO, chronic pharmacological treatment), ii) measure the quantitatives changes in ion channel transcriptome (40 voltage-dependent ion channels) associated with these perturbations and iii) determine the mathematical relationships between quantitative changes in ion channel expression and electrical phenotype. Although focused on dopaminergic neurons, this project will provide a general framework that could be applied to any type of excitable cell to decipher its code of robustness.
Max ERC Funding
1 972 797 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym DIABLO
Project Mechanisms of Developmental and Injury-related Axon Branch Loss
Researcher (PI) Thomas Misgeld
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary My aim is to explore the subcellular (i.e. cell biological and molecular) mechanisms of axon loss in the developing and diseased mammalian nervous system. Axon loss not only sculpts neuronal networks in development, but also occurs early in numerous neurological diseases. Indeed, the life-time risk for diseases with an “axonopathic” component approaches 50%. Pathological axon loss likely involves aberrant activation of developmental programs – just as cell death in disease often takes the form of apoptosis, another prominent regressive event in neural development. Over the past few years, the first molecular pathways have emerged for one form of axon loss, Wallerian degeneration, which removes entire axon arbors after severing. However, Wallerian degeneration is of limited clinical significance – because the axon is cut and hence incapacitated before it is lost – and appears to play only minor roles in development. In contrast, “non-Wallerian” forms of axon loss that selectively remove individual “aberrant” branches dominate during development (“axon branch loss”). Due to the technical challenge of studying axon loss in the complex environment of the developing mammalian nervous system, the subcellular events that precede such non-Wallerian forms of axon branch loss are poorly understood, even though this phenomenon – when pathologically reactivated – likely contributes to axonal pathology in many neurological disorders. Over the past years, in parallel work on axon development and disease, my laboratory has devised functional imaging techniques that allow studying axon loss in vivo in the mammalian peripheral (PNS) and central nervous system (CNS) with subcellular resolution and molecular read-outs. Using these unique tools, I will address the following aims:
1 - Axon-intrinsic mechanisms of motor axon branch loss.
2 - Axon-glial mechanisms of motor axon branch loss.
3 - Axon branch loss during CNS development.
4 - Axon branch loss after CNS injury.
Summary
My aim is to explore the subcellular (i.e. cell biological and molecular) mechanisms of axon loss in the developing and diseased mammalian nervous system. Axon loss not only sculpts neuronal networks in development, but also occurs early in numerous neurological diseases. Indeed, the life-time risk for diseases with an “axonopathic” component approaches 50%. Pathological axon loss likely involves aberrant activation of developmental programs – just as cell death in disease often takes the form of apoptosis, another prominent regressive event in neural development. Over the past few years, the first molecular pathways have emerged for one form of axon loss, Wallerian degeneration, which removes entire axon arbors after severing. However, Wallerian degeneration is of limited clinical significance – because the axon is cut and hence incapacitated before it is lost – and appears to play only minor roles in development. In contrast, “non-Wallerian” forms of axon loss that selectively remove individual “aberrant” branches dominate during development (“axon branch loss”). Due to the technical challenge of studying axon loss in the complex environment of the developing mammalian nervous system, the subcellular events that precede such non-Wallerian forms of axon branch loss are poorly understood, even though this phenomenon – when pathologically reactivated – likely contributes to axonal pathology in many neurological disorders. Over the past years, in parallel work on axon development and disease, my laboratory has devised functional imaging techniques that allow studying axon loss in vivo in the mammalian peripheral (PNS) and central nervous system (CNS) with subcellular resolution and molecular read-outs. Using these unique tools, I will address the following aims:
1 - Axon-intrinsic mechanisms of motor axon branch loss.
2 - Axon-glial mechanisms of motor axon branch loss.
3 - Axon branch loss during CNS development.
4 - Axon branch loss after CNS injury.
Max ERC Funding
1 995 000 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym DPR-MODELS
Project C9orf72 repeat expansion in FTD/ALS - from mechanisms to therapeutic approaches
Researcher (PI) Dieter Johannes Edbauer
Host Institution (HI) DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary "Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases with overlapping genetics and pathology. The most common known cause is expansion of a GGGGCC repeat in the first intron of the gene C9orf72. I discovered that the repeat region is translated in all three reading frames into aggregating dipeptide-repeat (DPR) proteins despite its intronic localization and lack of an ATG start codon. DPR aggregates outnumber the previously identified TDP-43 inclusions in the hippocampus, cortex and cerebellum. Some patients exclusively show DPR pathology, strongly suggesting DPR production is a key pathomechanism in C9orf72 mutation carriers. However, we know next to nothing about the mechanisms of translation, toxicity, aggregation and clearance of DPR proteins. With this grant I will characterize this unusual pathomechanism in detail.
First, I will generate monoclonal antibodies for a comprehensive analysis of all DPR species to determine the best pathological correlate of disease progression. Insights from patients will drive mechanistic studies and will help to identify therapeutic targets within the DPR cascade. Second, I will develop cell culture models to identify the molecular pathways that determine the expression, toxicity and aggregation of DPR proteins. These models will be used to identify drugs that block all steps of the DPR cascade in pilot screens. Third, I will create transgenic mouse models expressing DPR proteins to rigorously validate the DPR hypothesis by comparing pathology and clinical symptoms of transgenic mice and human C9orf72 patients. Finally, these mouse models will be used to test promising compounds identified in cellular models in prevention and treatment trials. Moreover, I will analyse whether passive immunization with the newly developed monoclonal antibodies allows clearance of DPR proteins from the brain as it has been shown for other intracellular aggregating proteins such as a-synuclein."
Summary
"Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases with overlapping genetics and pathology. The most common known cause is expansion of a GGGGCC repeat in the first intron of the gene C9orf72. I discovered that the repeat region is translated in all three reading frames into aggregating dipeptide-repeat (DPR) proteins despite its intronic localization and lack of an ATG start codon. DPR aggregates outnumber the previously identified TDP-43 inclusions in the hippocampus, cortex and cerebellum. Some patients exclusively show DPR pathology, strongly suggesting DPR production is a key pathomechanism in C9orf72 mutation carriers. However, we know next to nothing about the mechanisms of translation, toxicity, aggregation and clearance of DPR proteins. With this grant I will characterize this unusual pathomechanism in detail.
First, I will generate monoclonal antibodies for a comprehensive analysis of all DPR species to determine the best pathological correlate of disease progression. Insights from patients will drive mechanistic studies and will help to identify therapeutic targets within the DPR cascade. Second, I will develop cell culture models to identify the molecular pathways that determine the expression, toxicity and aggregation of DPR proteins. These models will be used to identify drugs that block all steps of the DPR cascade in pilot screens. Third, I will create transgenic mouse models expressing DPR proteins to rigorously validate the DPR hypothesis by comparing pathology and clinical symptoms of transgenic mice and human C9orf72 patients. Finally, these mouse models will be used to test promising compounds identified in cellular models in prevention and treatment trials. Moreover, I will analyse whether passive immunization with the newly developed monoclonal antibodies allows clearance of DPR proteins from the brain as it has been shown for other intracellular aggregating proteins such as a-synuclein."
Max ERC Funding
1 991 000 €
Duration
Start date: 2014-05-01, End date: 2019-04-30
Project acronym EVONEURO
Project Evolution of olfactory circuits
Researcher (PI) Richard Roland Benton
Host Institution (HI) UNIVERSITE DE LAUSANNE
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary "Nervous systems have undergone remarkable diversification in their structure and function as animals have adapted to distinct ecological niches. What are the genetic mechanisms underlying neural circuit evolution? The project addresses this fundamental question in the Drosophila olfactory system, a superior ""evo-neuro"" model for several reasons: (i) as in mammals, the Drosophila olfactory system has a modular organization, with individual olfactory receptors functionally and anatomically defining discrete sensory circuits that can be traced from the periphery to the brain; (ii) these circuits are dynamically evolving, with frequent acquisition (and loss) of receptors, olfactory neurons and odor-evoked behaviors with the ever-changing landscape of environmental volatiles; (iii) Drosophila offers unparalleled experimental accessibility to visualize and manipulate neural circuits; (iv) a wealth of insect genomes permits comparative studies to relate intra- and interspecific genotypic and phenotypic variation. Five aims address distinct aspects of olfactory circuit evolution: 1. Evolution of receptor specificity; 2. Evolution of receptor expression; 3. Evolution of sensory neuron targeting; 4. Evolution of interneuron wiring; 5. Evolution of olfactory behavior. This multidisciplinary project uses cutting-edge approaches in comparative genomics, electrophysiology, neurogenetics, transcriptomics, behavioral tracking and population genetics. By addressing how particular olfactory circuits and behaviors have evolved in Drosophila, it will provide general insights into the genetic mechanisms of nervous system evolution relevant both for other brain regions and for other species. We also anticipate that determining how brains have been sculpted through random mutation and natural selection in the past may enable future directed manipulation of the connectivity and activity of neural circuits, to enhance our understanding of brains and our ability to repair them."
Summary
"Nervous systems have undergone remarkable diversification in their structure and function as animals have adapted to distinct ecological niches. What are the genetic mechanisms underlying neural circuit evolution? The project addresses this fundamental question in the Drosophila olfactory system, a superior ""evo-neuro"" model for several reasons: (i) as in mammals, the Drosophila olfactory system has a modular organization, with individual olfactory receptors functionally and anatomically defining discrete sensory circuits that can be traced from the periphery to the brain; (ii) these circuits are dynamically evolving, with frequent acquisition (and loss) of receptors, olfactory neurons and odor-evoked behaviors with the ever-changing landscape of environmental volatiles; (iii) Drosophila offers unparalleled experimental accessibility to visualize and manipulate neural circuits; (iv) a wealth of insect genomes permits comparative studies to relate intra- and interspecific genotypic and phenotypic variation. Five aims address distinct aspects of olfactory circuit evolution: 1. Evolution of receptor specificity; 2. Evolution of receptor expression; 3. Evolution of sensory neuron targeting; 4. Evolution of interneuron wiring; 5. Evolution of olfactory behavior. This multidisciplinary project uses cutting-edge approaches in comparative genomics, electrophysiology, neurogenetics, transcriptomics, behavioral tracking and population genetics. By addressing how particular olfactory circuits and behaviors have evolved in Drosophila, it will provide general insights into the genetic mechanisms of nervous system evolution relevant both for other brain regions and for other species. We also anticipate that determining how brains have been sculpted through random mutation and natural selection in the past may enable future directed manipulation of the connectivity and activity of neural circuits, to enhance our understanding of brains and our ability to repair them."
Max ERC Funding
1 999 920 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym F-TRACT
Project Functional Brain Tractography
Researcher (PI) Olivier David
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary "Single-pulse direct electrical stimulation of cortical regions in patients suffering from focal drug-resistant epilepsy who are explored using intracranial electrodes induces electrophysiological responses. Such cortico-cortical induced potentials can be used to infer functional and anatomical brain connectivity.
We will develop methods to analyse those responses using neuroimaging tools in order to create a new probabilistic atlas of functional tractography of the human brain, which will be made freely available to the clinical and neuroscience community. Several thousands of stimulation runs performed in several hundreds of patients will be included in the atlas database to reach a nearly full coverage of the human cortex (inclusion of 540 patients retrospectively and of 172 patients/year prospectively, from 8 French and 1 Czech epilepsy surgery centres). As a proof of concept, we generated for F-TRACT scientific document a preliminary database of 1535 stimulation runs performed in 35 adult patients. To illustrate the potential of our approach, in particular to refine neurobiological models of cognitive systems, we use here this preliminary atlas to demonstrate the asymmetry of the functional connectivity between Wernicke’s area and Broca’s area, two key nodes of the language network.
This new atlas of functional tractography will be very useful to understand how the brain works and to develop neurocomputational models at a large scale. It will also allow the development of new clinical tools for the presurgical evaluation of intractable epilepsy. It is very complementary to other structural and functional approaches, such as MRI diffusion and functional mapping derived from metabolic, optical and electromagnetic techniques. The open access to this unique atlas of functional tractography will allow to explore in the future its numerous properties in relation to distributed brain networks in the domains of neuroanatomy, neurocognition and neurophysiopathology."
Summary
"Single-pulse direct electrical stimulation of cortical regions in patients suffering from focal drug-resistant epilepsy who are explored using intracranial electrodes induces electrophysiological responses. Such cortico-cortical induced potentials can be used to infer functional and anatomical brain connectivity.
We will develop methods to analyse those responses using neuroimaging tools in order to create a new probabilistic atlas of functional tractography of the human brain, which will be made freely available to the clinical and neuroscience community. Several thousands of stimulation runs performed in several hundreds of patients will be included in the atlas database to reach a nearly full coverage of the human cortex (inclusion of 540 patients retrospectively and of 172 patients/year prospectively, from 8 French and 1 Czech epilepsy surgery centres). As a proof of concept, we generated for F-TRACT scientific document a preliminary database of 1535 stimulation runs performed in 35 adult patients. To illustrate the potential of our approach, in particular to refine neurobiological models of cognitive systems, we use here this preliminary atlas to demonstrate the asymmetry of the functional connectivity between Wernicke’s area and Broca’s area, two key nodes of the language network.
This new atlas of functional tractography will be very useful to understand how the brain works and to develop neurocomputational models at a large scale. It will also allow the development of new clinical tools for the presurgical evaluation of intractable epilepsy. It is very complementary to other structural and functional approaches, such as MRI diffusion and functional mapping derived from metabolic, optical and electromagnetic techniques. The open access to this unique atlas of functional tractography will allow to explore in the future its numerous properties in relation to distributed brain networks in the domains of neuroanatomy, neurocognition and neurophysiopathology."
Max ERC Funding
1 999 200 €
Duration
Start date: 2014-08-01, End date: 2019-07-31
Project acronym GCGXC
Project GenoChemetics: Gene eXpression enabling selective Chemical functionalisation of natural products
Researcher (PI) Rebecca Jane Miriam Goss
Host Institution (HI) THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS
Call Details Consolidator Grant (CoG), PE5, ERC-2013-CoG
Summary "We aim to consolidate a trans-disciplinary research programme in which synthetic biology is harnessed to enable synthetic chemistry. We will utilise this approach to expeditiously access series of previously intractable natural product analogues.
There is an urgent need for the discovery and development of new drugs and in particular new antibiotics. More than 13 million lives worldwide are currently claimed each year due to infectious diseases. Natural products provide an unparalleled starting point for drug discovery, with over 60% of anticancer agents and over 70% of antibiotics entering clinical trials in the last three decades being based on such compounds. In order to gain a full understanding as to how a drug works and in order to be able to generate compounds with improved biological activity and physicochemical properties the generation of analogues is essential. In recent years pharmaceutical industries have shied away from natural products due to the perceived synthetic intractability of libraries of natural product analogues and the misperception that it is not possible to carry out thorough structure activity relationship (SAR) assessment on such compounds. As a result of largely abandoning natural products, industries’ drug discovery pipelines are beginning to run dry; this is a particular concern when faced with the need to combat the ever-increasing problem of drug resistance and infectious disease.
We aim to challenge the misperception that natural products are not “med chemable” We are developing a new approach to natural product analogue synthesis. By introducing a gene from a foreign organism to complement existing natural product biosynthetic machinery we are able to introduce a chemically orthogonal, reactive and selectably chemically functionalisable handle into the natural product (the antithesis of a protecting group) - this reactive handle will enable us to carry out chemical modifications only at the site at which it is located."
Summary
"We aim to consolidate a trans-disciplinary research programme in which synthetic biology is harnessed to enable synthetic chemistry. We will utilise this approach to expeditiously access series of previously intractable natural product analogues.
There is an urgent need for the discovery and development of new drugs and in particular new antibiotics. More than 13 million lives worldwide are currently claimed each year due to infectious diseases. Natural products provide an unparalleled starting point for drug discovery, with over 60% of anticancer agents and over 70% of antibiotics entering clinical trials in the last three decades being based on such compounds. In order to gain a full understanding as to how a drug works and in order to be able to generate compounds with improved biological activity and physicochemical properties the generation of analogues is essential. In recent years pharmaceutical industries have shied away from natural products due to the perceived synthetic intractability of libraries of natural product analogues and the misperception that it is not possible to carry out thorough structure activity relationship (SAR) assessment on such compounds. As a result of largely abandoning natural products, industries’ drug discovery pipelines are beginning to run dry; this is a particular concern when faced with the need to combat the ever-increasing problem of drug resistance and infectious disease.
We aim to challenge the misperception that natural products are not “med chemable” We are developing a new approach to natural product analogue synthesis. By introducing a gene from a foreign organism to complement existing natural product biosynthetic machinery we are able to introduce a chemically orthogonal, reactive and selectably chemically functionalisable handle into the natural product (the antithesis of a protecting group) - this reactive handle will enable us to carry out chemical modifications only at the site at which it is located."
Max ERC Funding
1 981 272 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym HELENA
Project Heavy-Element Nanowires
Researcher (PI) Erik Petrus Antonius Maria Bakkers
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Consolidator Grant (CoG), PE5, ERC-2013-CoG
Summary "Nanowires are a powerful and versatile platform for a broad range of applications. Among all semiconductors, the heavy-elements materials exhibit the highest electron mobilities, strongest spin-orbit coupling and best thermoelectric properties. Nonetheless, heavy-element nanowires have been unexplored. With this proposal we unite the unique advantages of design freedom of nanowires with the special properties of heavy-element semiconductors. We specifically reveal the potential of heavy-element nanowires in the areas of thermoelectrics, and topological insulators. Using our strong track record in this area, we will pioneer the synthesis of this new class of materials and study their intrinsic materials properties. Starting point are nanowires of InSb and PbTe grown using the vapor-liquid-solid mechanism. Our aims are 1) to obtain highest-possible electron mobilities for these bottom-up fabricated materials by investigating new materials combinations of different semiconductor classes to effectively passivate the nanowire surface and we will eliminate impurities; 2) to investigate and optimize thermoelectric properties by developing advanced superlattice and core/shell nanowire structures where electronic and phononic transport is decoupled; and 3) to fabricate high-quality planar nanowire networks, which enable four-point electronic transport measurements and allow precisely determining carrier concentration and mobility. Besides the fundamentally interesting materials science, the heavy-element nanowires will have major impact on the fields of renewable energy, new (quasi) particles and quantum information processing. Recently, the first signatures of Majorana fermions have been observed in our InSb nanowires. With the proposed nanowire networks the special properties of this recently discovered particle can be tested for the first time."
Summary
"Nanowires are a powerful and versatile platform for a broad range of applications. Among all semiconductors, the heavy-elements materials exhibit the highest electron mobilities, strongest spin-orbit coupling and best thermoelectric properties. Nonetheless, heavy-element nanowires have been unexplored. With this proposal we unite the unique advantages of design freedom of nanowires with the special properties of heavy-element semiconductors. We specifically reveal the potential of heavy-element nanowires in the areas of thermoelectrics, and topological insulators. Using our strong track record in this area, we will pioneer the synthesis of this new class of materials and study their intrinsic materials properties. Starting point are nanowires of InSb and PbTe grown using the vapor-liquid-solid mechanism. Our aims are 1) to obtain highest-possible electron mobilities for these bottom-up fabricated materials by investigating new materials combinations of different semiconductor classes to effectively passivate the nanowire surface and we will eliminate impurities; 2) to investigate and optimize thermoelectric properties by developing advanced superlattice and core/shell nanowire structures where electronic and phononic transport is decoupled; and 3) to fabricate high-quality planar nanowire networks, which enable four-point electronic transport measurements and allow precisely determining carrier concentration and mobility. Besides the fundamentally interesting materials science, the heavy-element nanowires will have major impact on the fields of renewable energy, new (quasi) particles and quantum information processing. Recently, the first signatures of Majorana fermions have been observed in our InSb nanowires. With the proposed nanowire networks the special properties of this recently discovered particle can be tested for the first time."
Max ERC Funding
2 698 447 €
Duration
Start date: 2014-09-01, End date: 2019-08-31
Project acronym HMRI
Project Non-Invasive In-Vivo Histology in Health and Disease Using Magnetic Resonance Imaging (MRI)
Researcher (PI) Nikolaus Weiskopf
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary Understanding of the normal and diseased brain crucially depends on reliable knowledge of its microstructure. Important functions are mediated by small cortical units (columns) and even small changes in the microstructure can cause debilitating diseases. So far, this microstructure can only be determined using invasive methods such as, e.g., ex-vivo histology. This limits neuroscience, clinical research and diagnosis.
My research vision is to develop novel methods for high-resolution magnetic resonance imaging (MRI) at 3T-9.4T to reliably characterize and quantify the detailed microstructure of the human cortex.
This MRI-based histology will be used to investigate the cortical microstructure in health and focal cortical degeneration. Structure-function relationships in visual cortex will be elucidated in-vivo, particularly, ocular dominance columns and stripes. Specific microstructural changes in focal cortical degeneration due to Alzheimer’s disease and monocular blindness will be determined, including amyloid plaque imaging.
To resolve the subtle structures and disease related changes, which have not previously been delineated in-vivo by anatomical MRI, unprecedented isotropic imaging resolution of up to 250 µm is essential. Methods for high-resolution myelin and iron mapping will be developed from novel quantitative MRI approaches that I have previously established. Super-resolution diffusion and susceptibility imaging will be developed to capture the neuropil microstructure. Anatomical imaging will be complemented by advanced high-resolution functional MRI. The multi-modal MRI data will be integrated into a unified model of MRI contrasts, cortical anatomy and tissue microstructure.
My ambitious goal of developing in vivo MRI-based histology can only be achieved by an integrative approach combining innovations in MR physics, modelling and tailored (clinical) neuroscience experiments. If successful, the project will transform research and clinical imaging.
Summary
Understanding of the normal and diseased brain crucially depends on reliable knowledge of its microstructure. Important functions are mediated by small cortical units (columns) and even small changes in the microstructure can cause debilitating diseases. So far, this microstructure can only be determined using invasive methods such as, e.g., ex-vivo histology. This limits neuroscience, clinical research and diagnosis.
My research vision is to develop novel methods for high-resolution magnetic resonance imaging (MRI) at 3T-9.4T to reliably characterize and quantify the detailed microstructure of the human cortex.
This MRI-based histology will be used to investigate the cortical microstructure in health and focal cortical degeneration. Structure-function relationships in visual cortex will be elucidated in-vivo, particularly, ocular dominance columns and stripes. Specific microstructural changes in focal cortical degeneration due to Alzheimer’s disease and monocular blindness will be determined, including amyloid plaque imaging.
To resolve the subtle structures and disease related changes, which have not previously been delineated in-vivo by anatomical MRI, unprecedented isotropic imaging resolution of up to 250 µm is essential. Methods for high-resolution myelin and iron mapping will be developed from novel quantitative MRI approaches that I have previously established. Super-resolution diffusion and susceptibility imaging will be developed to capture the neuropil microstructure. Anatomical imaging will be complemented by advanced high-resolution functional MRI. The multi-modal MRI data will be integrated into a unified model of MRI contrasts, cortical anatomy and tissue microstructure.
My ambitious goal of developing in vivo MRI-based histology can only be achieved by an integrative approach combining innovations in MR physics, modelling and tailored (clinical) neuroscience experiments. If successful, the project will transform research and clinical imaging.
Max ERC Funding
2 000 000 €
Duration
Start date: 2014-09-01, End date: 2019-08-31
Project acronym I-SURF
Project Inorganic surfactants with multifunctional heads
Researcher (PI) Sebastian Polarz
Host Institution (HI) UNIVERSITAT KONSTANZ
Call Details Consolidator Grant (CoG), PE5, ERC-2013-CoG
Summary "Surfactants are molecules of enormous scientific and technological importance, which are widely used as detergents, emulsifiers or for the preparation of diverse nanostructures. Fascinating abilities regarding the formation of self-organized structures, like micelles or liquid crystals, originate from their amphiphilic architecture, which comprises a polar head group linked to a hydrophobic chain. While almost all known surfactants are organic, a new family of surfactants is now emerging, which combine amphiphilic properties with the advanced functionality of transition metal building blocks. The current project aims at the synthesis of unique inorganic surfactants (I-SURFs), which contain multinuclear, charged metal-oxo entities as heads, and their exploration with regard to additional redox, catalytic or magnetic functionalities. A particular challenge is the creation of smart surfactant systems that can be controlled via external stimuli. While thermotropic liquid crystals and their adjustment in electric fields (enabling LCDs) have been studied in depth, very limited research concerns the control of self-assembled amphiphilic structures by use of magnetic fields. It is obvious that exposure to a magnetic field has inherent advantages over electric fields for controlling structures in water. I-SURFs with single-molecule magnets as heads will be thus prepared and studied. Another groundbreaking task is the creation of I-SURFs with additional catalytic activities. Since catalytic heads can be positioned via self-organization, for instance on the surface of micellar aggregates, catalytic relay systems can be assembled with a second catalytic species in proximity to the first. Thus, cooperative effects in catalytic tandem reactions will ultimately be observed. These examples show that frontier research on I-SURFs is of outstanding relevance for supramolecular science and will certainly pave the way toward new technological applications with great benefits to society."
Summary
"Surfactants are molecules of enormous scientific and technological importance, which are widely used as detergents, emulsifiers or for the preparation of diverse nanostructures. Fascinating abilities regarding the formation of self-organized structures, like micelles or liquid crystals, originate from their amphiphilic architecture, which comprises a polar head group linked to a hydrophobic chain. While almost all known surfactants are organic, a new family of surfactants is now emerging, which combine amphiphilic properties with the advanced functionality of transition metal building blocks. The current project aims at the synthesis of unique inorganic surfactants (I-SURFs), which contain multinuclear, charged metal-oxo entities as heads, and their exploration with regard to additional redox, catalytic or magnetic functionalities. A particular challenge is the creation of smart surfactant systems that can be controlled via external stimuli. While thermotropic liquid crystals and their adjustment in electric fields (enabling LCDs) have been studied in depth, very limited research concerns the control of self-assembled amphiphilic structures by use of magnetic fields. It is obvious that exposure to a magnetic field has inherent advantages over electric fields for controlling structures in water. I-SURFs with single-molecule magnets as heads will be thus prepared and studied. Another groundbreaking task is the creation of I-SURFs with additional catalytic activities. Since catalytic heads can be positioned via self-organization, for instance on the surface of micellar aggregates, catalytic relay systems can be assembled with a second catalytic species in proximity to the first. Thus, cooperative effects in catalytic tandem reactions will ultimately be observed. These examples show that frontier research on I-SURFs is of outstanding relevance for supramolecular science and will certainly pave the way toward new technological applications with great benefits to society."
Max ERC Funding
1 863 546 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
