Project acronym Amygdala Circuits
Project Amygdala Circuits for Appetitive Conditioning
Researcher (PI) Andreas Luthi
Host Institution (HI) FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Call Details Advanced Grant (AdG), LS5, ERC-2014-ADG
Summary The project outlined here addresses the fundamental question how the brain encodes and controls behavior. While we have a reasonable understanding of the role of entire brain areas in such processes, and of mechanisms at the molecular and synaptic levels, there is a big gap in our knowledge of how behavior is controlled at the level of defined neuronal circuits.
In natural environments, chances for survival depend on learning about possible aversive and appetitive outcomes and on the appropriate behavioral responses. Most studies addressing the underlying mechanisms at the level of neuronal circuits have focused on aversive learning, such as in Pavlovian fear conditioning. Understanding how activity in defined neuronal circuits mediates appetitive learning, as well as how these circuitries are shared and interact with aversive learning circuits, is a central question in the neuroscience of learning and memory and the focus of this grant application.
Using a multidisciplinary approach in mice, combining behavioral, in vivo and in vitro electrophysiological, imaging, optogenetic and state-of-the-art viral circuit tracing techniques, we aim at dissecting the neuronal circuitry of appetitive Pavlovian conditioning with a focus on the amygdala, a key brain region important for both aversive and appetitive learning. Ultimately, elucidating these mechanisms at the level of defined neurons and circuits is fundamental not only for an understanding of memory processes in the brain in general, but also to inform a mechanistic approach to psychiatric conditions associated with amygdala dysfunction and dysregulated emotional responses including anxiety and mood disorders.
Summary
The project outlined here addresses the fundamental question how the brain encodes and controls behavior. While we have a reasonable understanding of the role of entire brain areas in such processes, and of mechanisms at the molecular and synaptic levels, there is a big gap in our knowledge of how behavior is controlled at the level of defined neuronal circuits.
In natural environments, chances for survival depend on learning about possible aversive and appetitive outcomes and on the appropriate behavioral responses. Most studies addressing the underlying mechanisms at the level of neuronal circuits have focused on aversive learning, such as in Pavlovian fear conditioning. Understanding how activity in defined neuronal circuits mediates appetitive learning, as well as how these circuitries are shared and interact with aversive learning circuits, is a central question in the neuroscience of learning and memory and the focus of this grant application.
Using a multidisciplinary approach in mice, combining behavioral, in vivo and in vitro electrophysiological, imaging, optogenetic and state-of-the-art viral circuit tracing techniques, we aim at dissecting the neuronal circuitry of appetitive Pavlovian conditioning with a focus on the amygdala, a key brain region important for both aversive and appetitive learning. Ultimately, elucidating these mechanisms at the level of defined neurons and circuits is fundamental not only for an understanding of memory processes in the brain in general, but also to inform a mechanistic approach to psychiatric conditions associated with amygdala dysfunction and dysregulated emotional responses including anxiety and mood disorders.
Max ERC Funding
2 497 200 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym BOTMED
Project Microrobotics and Nanomedicine
Researcher (PI) Bradley James Nelson
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE7, ERC-2010-AdG_20100224
Summary The introduction of minimally invasive surgery in the 1980’s created a paradigm shift in surgical procedures. Health care is now in a position to make a more dramatic leap by integrating newly developed wireless microrobotic technologies with nanomedicine to perform precisely targeted, localized endoluminal techniques. Devices capable of entering the human body through natural orifices or small incisions to deliver drugs, perform diagnostic procedures, and excise and repair tissue will be used. These new procedures will result in less trauma to the patient and faster recovery times, and will enable new therapies that have not yet been conceived. In order to realize this, many new technologies must be developed and synergistically integrated, and medical therapies for which the technology will prove successful must be aggressively pursued.
This proposed project will result in the realization of animal trials in which wireless microrobotic devices will be used to investigate a variety of extremely delicate ophthalmic therapies. The therapies to be pursued include the delivery of tissue plasminogen activator (t-PA) to blocked retinal veins, the peeling of epiretinal membranes from the retina, and the development of diagnostic procedures based on mapping oxygen concentration at the vitreous-retina interface. With successful animal trials, a path to human trials and commercialization will follow. Clearly, many systems in the body have the potential to benefit from the endoluminal technologies that this project considers, including the digestive system, the circulatory system, the urinary system, the central nervous system, the respiratory system, the female reproductive system and even the fetus. Microrobotic retinal therapies will greatly illuminate the potential that the integration of microrobotics and nanomedicine holds for society, and greatly accelerate this trend in Europe.
Summary
The introduction of minimally invasive surgery in the 1980’s created a paradigm shift in surgical procedures. Health care is now in a position to make a more dramatic leap by integrating newly developed wireless microrobotic technologies with nanomedicine to perform precisely targeted, localized endoluminal techniques. Devices capable of entering the human body through natural orifices or small incisions to deliver drugs, perform diagnostic procedures, and excise and repair tissue will be used. These new procedures will result in less trauma to the patient and faster recovery times, and will enable new therapies that have not yet been conceived. In order to realize this, many new technologies must be developed and synergistically integrated, and medical therapies for which the technology will prove successful must be aggressively pursued.
This proposed project will result in the realization of animal trials in which wireless microrobotic devices will be used to investigate a variety of extremely delicate ophthalmic therapies. The therapies to be pursued include the delivery of tissue plasminogen activator (t-PA) to blocked retinal veins, the peeling of epiretinal membranes from the retina, and the development of diagnostic procedures based on mapping oxygen concentration at the vitreous-retina interface. With successful animal trials, a path to human trials and commercialization will follow. Clearly, many systems in the body have the potential to benefit from the endoluminal technologies that this project considers, including the digestive system, the circulatory system, the urinary system, the central nervous system, the respiratory system, the female reproductive system and even the fetus. Microrobotic retinal therapies will greatly illuminate the potential that the integration of microrobotics and nanomedicine holds for society, and greatly accelerate this trend in Europe.
Max ERC Funding
2 498 044 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym BRAINCOMPATH
Project Mesoscale Brain Dynamics: Computing with Neuronal Pathways
Researcher (PI) Fritjof Helmchen
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Advanced Grant (AdG), LS5, ERC-2014-ADG
Summary Brain computations rely on proper signal flow through the complex network of connected brain regions. Despite a wealth of anatomical and functional data – from microscopic to macroscopic scale – we still poorly understand the principles of how signal flow is routed through neuronal networks to generate appropriate behavior. Brain dynamics on the 'mesoscopic' scale, the intermediate level where local microcircuits communicate via axonal pathways, has remained a particular blind spot of research as it has been difficult to access under in vivo conditions. Here, I propose to tackle the mesoscopic level of brain dynamics both experimentally and theoretically, adopting a fresh perspective centered on neuronal pathway dynamics. Experimentally, we will utilize and further advance state-of-the-art genetic and optical techniques to create a toolbox for measuring and manipulating signal flow in pathway networks across a broad range of temporal scales. In particular, we will improve fiber-optic based methods for probing the activity of either individual or multiple neuronal pathways with high specificity. Using these tools we will set out to reveal mesoscopic brain dynamics across relevant cortical and subcortical regions in awake, behaving mice. Specifically, we will investigate sensorimotor learning for a reward-based texture discrimination task and rapid sensorimotor control during skilled locomotion. Moreover, by combining fiber-optic methods with two-photon microscopy and fMRI, respectively, we will start linking the meso-level to the micro- and macro-levels. Throughout the project, experiments will be complemented by computational approaches to analyse data, model pathway dynamics, and conceptualize a formal theory of mesoscopic dynamics. This project may transform the field by bridging the hierarchical brain levels and opening significant new avenues to assess physiological as well as pathological signal flow in the brain.
Summary
Brain computations rely on proper signal flow through the complex network of connected brain regions. Despite a wealth of anatomical and functional data – from microscopic to macroscopic scale – we still poorly understand the principles of how signal flow is routed through neuronal networks to generate appropriate behavior. Brain dynamics on the 'mesoscopic' scale, the intermediate level where local microcircuits communicate via axonal pathways, has remained a particular blind spot of research as it has been difficult to access under in vivo conditions. Here, I propose to tackle the mesoscopic level of brain dynamics both experimentally and theoretically, adopting a fresh perspective centered on neuronal pathway dynamics. Experimentally, we will utilize and further advance state-of-the-art genetic and optical techniques to create a toolbox for measuring and manipulating signal flow in pathway networks across a broad range of temporal scales. In particular, we will improve fiber-optic based methods for probing the activity of either individual or multiple neuronal pathways with high specificity. Using these tools we will set out to reveal mesoscopic brain dynamics across relevant cortical and subcortical regions in awake, behaving mice. Specifically, we will investigate sensorimotor learning for a reward-based texture discrimination task and rapid sensorimotor control during skilled locomotion. Moreover, by combining fiber-optic methods with two-photon microscopy and fMRI, respectively, we will start linking the meso-level to the micro- and macro-levels. Throughout the project, experiments will be complemented by computational approaches to analyse data, model pathway dynamics, and conceptualize a formal theory of mesoscopic dynamics. This project may transform the field by bridging the hierarchical brain levels and opening significant new avenues to assess physiological as well as pathological signal flow in the brain.
Max ERC Funding
2 498 915 €
Duration
Start date: 2016-02-01, End date: 2021-01-31
Project acronym BROADimmune
Project Structural, genetic and functional analyses of broadly neutralizing antibodies against human pathogens
Researcher (PI) Antonio Lanzavecchia
Host Institution (HI) FONDAZIONE PER L ISTITUTO DI RICERCA IN BIOMEDICINA
Call Details Advanced Grant (AdG), LS6, ERC-2014-ADG
Summary The overall goal of this project is to understand the molecular mechanisms that lead to the generation of potent and broadly neutralizing antibodies against medically relevant pathogens, and to identify the factors that limit their production in response to infection or vaccination with current vaccines. We will use high-throughput cellular screens to isolate from immune donors clonally related antibodies to different sites of influenza hemagglutinin, which will be fully characterized and sequenced in order to reconstruct their developmental pathways. Using this approach, we will ask fundamental questions with regards to the role of somatic mutations in affinity maturation and intraclonal diversification, which in some cases may lead to the generation of autoantibodies. We will combine crystallography and long time-scale molecular dynamics simulation to understand how mutations can increase affinity and broaden antibody specificity. By mapping the B and T cell response to all sites and conformations of influenza hemagglutinin, we will uncover the factors, such as insufficient T cell help or the instability of the pre-fusion hemagglutinin, that may limit the generation of broadly neutralizing antibodies. We will also perform a broad analysis of the antibody response to erythrocytes infected by P. falciparum to identify conserved epitopes on the parasite and to unravel the role of an enigmatic V gene that appears to be involved in response to blood-stage parasites. The hypotheses tested are strongly supported by preliminary observations from our own laboratory. While these studies will contribute to our understanding of B cell biology, the results obtained will also have translational implications for the development of potent and broad-spectrum antibodies, for the definition of correlates of protection, and for improving vaccine design.
Summary
The overall goal of this project is to understand the molecular mechanisms that lead to the generation of potent and broadly neutralizing antibodies against medically relevant pathogens, and to identify the factors that limit their production in response to infection or vaccination with current vaccines. We will use high-throughput cellular screens to isolate from immune donors clonally related antibodies to different sites of influenza hemagglutinin, which will be fully characterized and sequenced in order to reconstruct their developmental pathways. Using this approach, we will ask fundamental questions with regards to the role of somatic mutations in affinity maturation and intraclonal diversification, which in some cases may lead to the generation of autoantibodies. We will combine crystallography and long time-scale molecular dynamics simulation to understand how mutations can increase affinity and broaden antibody specificity. By mapping the B and T cell response to all sites and conformations of influenza hemagglutinin, we will uncover the factors, such as insufficient T cell help or the instability of the pre-fusion hemagglutinin, that may limit the generation of broadly neutralizing antibodies. We will also perform a broad analysis of the antibody response to erythrocytes infected by P. falciparum to identify conserved epitopes on the parasite and to unravel the role of an enigmatic V gene that appears to be involved in response to blood-stage parasites. The hypotheses tested are strongly supported by preliminary observations from our own laboratory. While these studies will contribute to our understanding of B cell biology, the results obtained will also have translational implications for the development of potent and broad-spectrum antibodies, for the definition of correlates of protection, and for improving vaccine design.
Max ERC Funding
1 867 500 €
Duration
Start date: 2015-10-01, End date: 2020-09-30
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 COMCOM
Project Communication and Computation - Two Sides of One Tapestry
Researcher (PI) Michael Christoph Gastpar
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), PE7, ERC-2010-StG_20091028
Summary Networks have been studied in depth for several decades, but one aspect has received little attention: Interference. Most networks use clever algorithms to avoid interference, and this strategy has proved effective for traditional supply-chain or wired communication networks. However, the emergence of wireless networks revealed that simply avoiding interference leads to significant performance loss. A wealth of cooperative communication strategies have recently been developed to address this issue. Two fundamental roadblocks are emerging: First, it is ultimately unclear how to integrate cooperative techniques into the larger fabric of networks (short of case-by-case redesigns); and second, the lack of source/channel separation in networks (i.e., more bits do not imply better end-to-end signal quality) calls for ever more specialized cooperative techniques.
This proposal advocates a new understanding of interference as computation: Interference garbles together inputs to produce an output. This can be thought of as a certain computation, perhaps subject to noise or other stochastic effects. The proposed work will develop strategies that permit to exploit this computational potential. Building on these ``computation codes,'' an enhanced physical layer is proposed: Rather than only forwarding bits, the revised physical layer can also forward functions from several transmitting nodes to a receiver, much more efficiently than the full information. Near-seamless integration into the fabric of existing network architectures is thus possible, providing a solution for the first roadblock. In response to the second roadblock, computation codes suggest new computational primitives as fundamental currencies of information.
Summary
Networks have been studied in depth for several decades, but one aspect has received little attention: Interference. Most networks use clever algorithms to avoid interference, and this strategy has proved effective for traditional supply-chain or wired communication networks. However, the emergence of wireless networks revealed that simply avoiding interference leads to significant performance loss. A wealth of cooperative communication strategies have recently been developed to address this issue. Two fundamental roadblocks are emerging: First, it is ultimately unclear how to integrate cooperative techniques into the larger fabric of networks (short of case-by-case redesigns); and second, the lack of source/channel separation in networks (i.e., more bits do not imply better end-to-end signal quality) calls for ever more specialized cooperative techniques.
This proposal advocates a new understanding of interference as computation: Interference garbles together inputs to produce an output. This can be thought of as a certain computation, perhaps subject to noise or other stochastic effects. The proposed work will develop strategies that permit to exploit this computational potential. Building on these ``computation codes,'' an enhanced physical layer is proposed: Rather than only forwarding bits, the revised physical layer can also forward functions from several transmitting nodes to a receiver, much more efficiently than the full information. Near-seamless integration into the fabric of existing network architectures is thus possible, providing a solution for the first roadblock. In response to the second roadblock, computation codes suggest new computational primitives as fundamental currencies of information.
Max ERC Funding
1 776 473 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
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 CTLANDROS
Project Reactive Oxygen Species in CTL-mediated Cell Death: from Mechanism to Applications
Researcher (PI) Denis Martinvalet
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Starting Grant (StG), LS6, ERC-2010-StG_20091118
Summary Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells release granzyme and perforin from cytotoxic granules into the immune synapse to induce apoptosis of target cells that are either virus-infected or cancerous. Granzyme A activates a caspase-independent apoptotic pathway and induces mitochondrial damage characterized by superoxide anion production and loss of the mitochondrial transmembrane potential, without disrupting the integrity of the mitochondrial outer membrane; while causing single-stranded DNA damage. GzmB induces both caspase-dependent and caspase-independent cell death. In the caspase-dependent pathway, mitochondrial functions are altered as evidenced by the loss of mitochondrial transmembrane potential and the generation of reactive oxygen species (ROS). The mitochondrial outer membrane (MOM) is disrupted, resulting in the release of apoptogenic factors. To date, research on mitochondrial-dependent apoptosis has focused on mitochondrial outer membrane permeabilization (MOMP) however whether the generation of ROS is incidental or essential to the execution of apoptosis remains unclear. Like human GzmA, human GzmB promotes cell death in a ROS-dependent manner. Preliminary data suggest that human GzmB can induce ROS in a MOMP-independent manner as Bax and Bak double knockout MEF cells treated with human GzmB and perforin still display a robust ROS production and dye in an ROS-dependent manner. Since GzmA and GzmB induce cell death in a ROS-dependent manner, we hypothesize that oxygen free radicals are central to the execution of programmed cell death induced by the cytotoxic granules. Therefore, the goal of this proposal is to dissect the key molecular events triggered by ROS that lead to Citotoxic Tcell-induced target cell death. A combination of biochemical, genetic and proteomic approaches in association with Electron Spin Resonance (ESR) spectroscopy methodology will be used to unravel the essential role ROS play in CTL-mediated killing.
Summary
Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells release granzyme and perforin from cytotoxic granules into the immune synapse to induce apoptosis of target cells that are either virus-infected or cancerous. Granzyme A activates a caspase-independent apoptotic pathway and induces mitochondrial damage characterized by superoxide anion production and loss of the mitochondrial transmembrane potential, without disrupting the integrity of the mitochondrial outer membrane; while causing single-stranded DNA damage. GzmB induces both caspase-dependent and caspase-independent cell death. In the caspase-dependent pathway, mitochondrial functions are altered as evidenced by the loss of mitochondrial transmembrane potential and the generation of reactive oxygen species (ROS). The mitochondrial outer membrane (MOM) is disrupted, resulting in the release of apoptogenic factors. To date, research on mitochondrial-dependent apoptosis has focused on mitochondrial outer membrane permeabilization (MOMP) however whether the generation of ROS is incidental or essential to the execution of apoptosis remains unclear. Like human GzmA, human GzmB promotes cell death in a ROS-dependent manner. Preliminary data suggest that human GzmB can induce ROS in a MOMP-independent manner as Bax and Bak double knockout MEF cells treated with human GzmB and perforin still display a robust ROS production and dye in an ROS-dependent manner. Since GzmA and GzmB induce cell death in a ROS-dependent manner, we hypothesize that oxygen free radicals are central to the execution of programmed cell death induced by the cytotoxic granules. Therefore, the goal of this proposal is to dissect the key molecular events triggered by ROS that lead to Citotoxic Tcell-induced target cell death. A combination of biochemical, genetic and proteomic approaches in association with Electron Spin Resonance (ESR) spectroscopy methodology will be used to unravel the essential role ROS play in CTL-mediated killing.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
Project acronym ESKIN
Project Stretchable Electronic Skins
Researcher (PI) Stephanie Perichon Ep Lacour
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Starting Grant (StG), PE7, ERC-2010-StG_20091028
Summary Future electronic systems will be soft and elastic. I propose to explore the materials, technology and integration of stretchable electronic systems, which will transform at will, evenly coat a spherical lens, or smoothly interface with a delicate biological organ. Electronics will be anywhere as well as everywhere. The proposed programme has the potential to emulate yet another revolution in the microelectronics industry and trigger transformations in the biomedical sector.
The ESKIN programme is an ambitious and highly interdisciplinary endeavour requiring expertise at the frontier of engineering, material sciences, biotechnology and neuroscience. Stretchability in an electronic system is its ability to negotiate mechanical deformations without letting them interfere with its electrical functionality. This is a novel and challenging demand on electronic device technology, which has, to date, mainly pushed for smaller scale fabrication and increased performance. Furthermore the natural compliance of biological tissues and cells calls for softer electronic biomedical interfaces. Overcoming the hard to soft mechanical mismatch will, without doubt, open up new horizons in biomedical research and its related industries.
The manufacture of stretchable electronic skins will then require working out the underlying science and technology for active device materials on soft, elastic substrates. This capability will further be implemented to demonstrate various soft and elastic electronic systems ranging from stretchable displays to long-term neural implants. My philosophy is to exploit as much as possible current micro/nanofabrication techniques available for hard surfaces but to tailor them to soft surfaces , optimizing and improving them where needed, in order to ensure rapid transition to worldwide distributed consumer and healthcare products.
Summary
Future electronic systems will be soft and elastic. I propose to explore the materials, technology and integration of stretchable electronic systems, which will transform at will, evenly coat a spherical lens, or smoothly interface with a delicate biological organ. Electronics will be anywhere as well as everywhere. The proposed programme has the potential to emulate yet another revolution in the microelectronics industry and trigger transformations in the biomedical sector.
The ESKIN programme is an ambitious and highly interdisciplinary endeavour requiring expertise at the frontier of engineering, material sciences, biotechnology and neuroscience. Stretchability in an electronic system is its ability to negotiate mechanical deformations without letting them interfere with its electrical functionality. This is a novel and challenging demand on electronic device technology, which has, to date, mainly pushed for smaller scale fabrication and increased performance. Furthermore the natural compliance of biological tissues and cells calls for softer electronic biomedical interfaces. Overcoming the hard to soft mechanical mismatch will, without doubt, open up new horizons in biomedical research and its related industries.
The manufacture of stretchable electronic skins will then require working out the underlying science and technology for active device materials on soft, elastic substrates. This capability will further be implemented to demonstrate various soft and elastic electronic systems ranging from stretchable displays to long-term neural implants. My philosophy is to exploit as much as possible current micro/nanofabrication techniques available for hard surfaces but to tailor them to soft surfaces , optimizing and improving them where needed, in order to ensure rapid transition to worldwide distributed consumer and healthcare products.
Max ERC Funding
1 499 738 €
Duration
Start date: 2011-03-01, End date: 2016-02-29
Project acronym FUN-SP
Project A functional framework for sparse, non-gaussian signal processing and bioimaging
Researcher (PI) Michael Unser
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Advanced Grant (AdG), PE7, ERC-2010-AdG_20100224
Summary "In recent years, the research focus in signal processing has shifted away from the classical linear paradigm, which is intimately linked with the theory of stationary Gaussian processes. Instead of considering Fourier transforms and performing quadratic optimization, researchers are presently favoring wavelet-like representations and have adopted ”sparsity” as design paradigm.
Our ambition is to develop a unifying operator-based framework for signal processing that would provide the ``sparse"" counterpart of the classical theory, which is currently missing. To that end, we shall specify and investigate sparse stochastic processes that are continuously-defined and ruled by differential equations, and construct corresponding wavelet-like sparsifying transforms. Our hope is to be able to rigorously connect non-quadratic regularization and sparsity-constrained optimization to well-defined continuous-domain statistical models. We also want to develop a novel Lie-group formalism for the design of steerable, signal-adapted wavelet transforms with improved invariance and sparsifying properties, both in 2-D and 3-D.
We shall use these tools to define new reversible image representations in terms of singular points (contours and keypoints) and to develop novel algorithms for 3-D biomedical image analysis. In close collaboration with imaging scientists, we shall apply our framework to the development of new 3-D reconstruction algorithms for emerging bioimaging modalities such as fluorescence deconvolution microscopy, digital holography microscopy, X-ray phase-contrast microscopy, and advanced MRI."
Summary
"In recent years, the research focus in signal processing has shifted away from the classical linear paradigm, which is intimately linked with the theory of stationary Gaussian processes. Instead of considering Fourier transforms and performing quadratic optimization, researchers are presently favoring wavelet-like representations and have adopted ”sparsity” as design paradigm.
Our ambition is to develop a unifying operator-based framework for signal processing that would provide the ``sparse"" counterpart of the classical theory, which is currently missing. To that end, we shall specify and investigate sparse stochastic processes that are continuously-defined and ruled by differential equations, and construct corresponding wavelet-like sparsifying transforms. Our hope is to be able to rigorously connect non-quadratic regularization and sparsity-constrained optimization to well-defined continuous-domain statistical models. We also want to develop a novel Lie-group formalism for the design of steerable, signal-adapted wavelet transforms with improved invariance and sparsifying properties, both in 2-D and 3-D.
We shall use these tools to define new reversible image representations in terms of singular points (contours and keypoints) and to develop novel algorithms for 3-D biomedical image analysis. In close collaboration with imaging scientists, we shall apply our framework to the development of new 3-D reconstruction algorithms for emerging bioimaging modalities such as fluorescence deconvolution microscopy, digital holography microscopy, X-ray phase-contrast microscopy, and advanced MRI."
Max ERC Funding
2 106 994 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
