Project acronym 3D-nanoMorph
Project Label-free 3D morphological nanoscopy for studying sub-cellular dynamics in live cancer cells with high spatio-temporal resolution
Researcher (PI) Krishna AGARWAL
Host Institution (HI) UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET
Call Details Starting Grant (StG), PE7, ERC-2018-STG
Summary Label-free optical nanoscopy, free from photobleaching and photochemical toxicity of fluorescence labels and yielding 3D morphological resolution of <50 nm, is the future of live cell imaging. 3D-nanoMorph breaks the diffraction barrier and shifts the paradigm in label-free nanoscopy, providing isotropic 3D resolution of <50 nm. To achieve this, 3D-nanoMorph performs non-linear inverse scattering for the first time in nanoscopy and decodes scattering between sub-cellular structures (organelles).
3D-nanoMorph innovatively devises complementary roles of light measurement system and computational nanoscopy algorithm. A novel illumination system and a novel light collection system together enable measurement of only the most relevant intensity component and create a fresh perspective about label-free measurements. A new computational nanoscopy approach employs non-linear inverse scattering. Harnessing non-linear inverse scattering for resolution enhancement in nanoscopy opens new possibilities in label-free 3D nanoscopy.
I will apply 3D-nanoMorph to study organelle degradation (autophagy) in live cancer cells over extended duration with high spatial and temporal resolution, presently limited by the lack of high-resolution label-free 3D morphological nanoscopy. Successful 3D mapping of nanoscale biological process of autophagy will open new avenues for cancer treatment and showcase 3D-nanoMorph for wider applications.
My cross-disciplinary expertise of 14 years spanning inverse problems, electromagnetism, optical microscopy, integrated optics and live cell nanoscopy paves path for successful implementation of 3D-nanoMorph.
Summary
Label-free optical nanoscopy, free from photobleaching and photochemical toxicity of fluorescence labels and yielding 3D morphological resolution of <50 nm, is the future of live cell imaging. 3D-nanoMorph breaks the diffraction barrier and shifts the paradigm in label-free nanoscopy, providing isotropic 3D resolution of <50 nm. To achieve this, 3D-nanoMorph performs non-linear inverse scattering for the first time in nanoscopy and decodes scattering between sub-cellular structures (organelles).
3D-nanoMorph innovatively devises complementary roles of light measurement system and computational nanoscopy algorithm. A novel illumination system and a novel light collection system together enable measurement of only the most relevant intensity component and create a fresh perspective about label-free measurements. A new computational nanoscopy approach employs non-linear inverse scattering. Harnessing non-linear inverse scattering for resolution enhancement in nanoscopy opens new possibilities in label-free 3D nanoscopy.
I will apply 3D-nanoMorph to study organelle degradation (autophagy) in live cancer cells over extended duration with high spatial and temporal resolution, presently limited by the lack of high-resolution label-free 3D morphological nanoscopy. Successful 3D mapping of nanoscale biological process of autophagy will open new avenues for cancer treatment and showcase 3D-nanoMorph for wider applications.
My cross-disciplinary expertise of 14 years spanning inverse problems, electromagnetism, optical microscopy, integrated optics and live cell nanoscopy paves path for successful implementation of 3D-nanoMorph.
Max ERC Funding
1 499 999 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym ADDICTIONCIRCUITS
Project Drug addiction: molecular changes in reward and aversion circuits
Researcher (PI) Nils David Engblom
Host Institution (HI) LINKOPINGS UNIVERSITET
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary Our affective and motivational state is important for our decisions, actions and quality of life. Many pathological conditions affect this state. For example, addictive drugs are hyperactivating the reward system and trigger a strong motivation for continued drug intake, whereas many somatic and psychiatric diseases lead to an aversive state, characterized by loss of motivation. I will study specific neural circuits and mechanisms underlying reward and aversion, and how pathological signaling in these systems can trigger relapse in drug addiction.
Given the important role of the dopaminergic neurons in the midbrain for many aspects of reward signaling, I will study how synaptic plasticity in these cells, and in their target neurons in the striatum, contribute to relapse in drug seeking. I will also study the circuits underlying aversion. Little is known about these circuits, but my hypothesis is that an important component of aversion is signaled by a specific neuronal population in the brainstem parabrachial nucleus, projecting to the central amygdala. We will test this hypothesis and also determine how this aversion circuit contributes to the persistence of addiction and to relapse.
To dissect this complicated system, I am developing new genetic methods for manipulating and visualizing specific functional circuits in the mouse brain. My unique combination of state-of-the-art competence in transgenics and cutting edge knowledge in the anatomy and functional organization of the circuits behind reward and aversion should allow me to decode these systems, linking discrete circuits to behavior.
Collectively, the results will indicate how signals encoding aversion and reward are integrated to control addictive behavior and they may identify novel avenues for treatment of drug addiction as well as aversion-related symptoms affecting patients with chronic inflammatory conditions and cancer.
Summary
Our affective and motivational state is important for our decisions, actions and quality of life. Many pathological conditions affect this state. For example, addictive drugs are hyperactivating the reward system and trigger a strong motivation for continued drug intake, whereas many somatic and psychiatric diseases lead to an aversive state, characterized by loss of motivation. I will study specific neural circuits and mechanisms underlying reward and aversion, and how pathological signaling in these systems can trigger relapse in drug addiction.
Given the important role of the dopaminergic neurons in the midbrain for many aspects of reward signaling, I will study how synaptic plasticity in these cells, and in their target neurons in the striatum, contribute to relapse in drug seeking. I will also study the circuits underlying aversion. Little is known about these circuits, but my hypothesis is that an important component of aversion is signaled by a specific neuronal population in the brainstem parabrachial nucleus, projecting to the central amygdala. We will test this hypothesis and also determine how this aversion circuit contributes to the persistence of addiction and to relapse.
To dissect this complicated system, I am developing new genetic methods for manipulating and visualizing specific functional circuits in the mouse brain. My unique combination of state-of-the-art competence in transgenics and cutting edge knowledge in the anatomy and functional organization of the circuits behind reward and aversion should allow me to decode these systems, linking discrete circuits to behavior.
Collectively, the results will indicate how signals encoding aversion and reward are integrated to control addictive behavior and they may identify novel avenues for treatment of drug addiction as well as aversion-related symptoms affecting patients with chronic inflammatory conditions and cancer.
Max ERC Funding
1 500 000 €
Duration
Start date: 2010-10-01, End date: 2015-09-30
Project acronym ATMOGAIN
Project Atmospheric Gas-Aerosol Interface:
From Fundamental Theory to Global Effects
Researcher (PI) Ilona Anniina Riipinen
Host Institution (HI) STOCKHOLMS UNIVERSITET
Call Details Starting Grant (StG), PE10, ERC-2011-StG_20101014
Summary Atmospheric aerosol particles are a major player in the earth system: they impact the climate by scattering and absorbing solar radiation, as well as regulating the properties of clouds. On regional scales aerosol particles are among the main pollutants deteriorating air quality. Capturing the impact of aerosols is one of the main challenges in understanding the driving forces behind changing climate and air quality.
Atmospheric aerosol numbers are governed by the ultrafine (< 100 nm in diameter) particles. Most of these particles have been formed from atmospheric vapours, and their fate and impacts are governed by the mass transport processes between the gas and particulate phases. These transport processes are currently poorly understood. Correct representation of the aerosol growth/shrinkage by condensation/evaporation of atmospheric vapours is thus a prerequisite for capturing the evolution and impacts of aerosols.
I propose to start a research group that will address the major current unknowns in atmospheric ultrafine particle growth and evaporation. First, we will develop a unified theoretical framework to describe the mass accommodation processes at aerosol surfaces, aiming to resolve the current ambiguity with respect to the uptake of atmospheric vapours by aerosols. Second, we will study the condensational properties of selected organic compounds and their mixtures. Organic compounds are known to contribute significantly to atmospheric aerosol growth, but the properties that govern their condensation, such as saturation vapour pressures and activities, are largely unknown. Third, we aim to resolve the gas and particulate phase processes that govern the growth of realistic atmospheric aerosol. Fourth, we will parameterize ultrafine aerosol growth, implement the parameterizations to chemical transport models, and quantify the impact of these condensation and evaporation processes on global and regional aerosol budgets.
Summary
Atmospheric aerosol particles are a major player in the earth system: they impact the climate by scattering and absorbing solar radiation, as well as regulating the properties of clouds. On regional scales aerosol particles are among the main pollutants deteriorating air quality. Capturing the impact of aerosols is one of the main challenges in understanding the driving forces behind changing climate and air quality.
Atmospheric aerosol numbers are governed by the ultrafine (< 100 nm in diameter) particles. Most of these particles have been formed from atmospheric vapours, and their fate and impacts are governed by the mass transport processes between the gas and particulate phases. These transport processes are currently poorly understood. Correct representation of the aerosol growth/shrinkage by condensation/evaporation of atmospheric vapours is thus a prerequisite for capturing the evolution and impacts of aerosols.
I propose to start a research group that will address the major current unknowns in atmospheric ultrafine particle growth and evaporation. First, we will develop a unified theoretical framework to describe the mass accommodation processes at aerosol surfaces, aiming to resolve the current ambiguity with respect to the uptake of atmospheric vapours by aerosols. Second, we will study the condensational properties of selected organic compounds and their mixtures. Organic compounds are known to contribute significantly to atmospheric aerosol growth, but the properties that govern their condensation, such as saturation vapour pressures and activities, are largely unknown. Third, we aim to resolve the gas and particulate phase processes that govern the growth of realistic atmospheric aerosol. Fourth, we will parameterize ultrafine aerosol growth, implement the parameterizations to chemical transport models, and quantify the impact of these condensation and evaporation processes on global and regional aerosol budgets.
Max ERC Funding
1 498 099 €
Duration
Start date: 2011-09-01, End date: 2016-08-31
Project acronym BrainInBrain
Project Neural circuits underlying complex brain function across animals - from conserved core concepts to specializations defining a species’ identity
Researcher (PI) Stanley HEINZE
Host Institution (HI) LUNDS UNIVERSITET
Call Details Starting Grant (StG), LS5, ERC-2016-STG
Summary The core function of all brains is to compute the current state of the world, compare it to the desired state of the world and select motor programs that drive behavior minimizing any mismatch. The circuits underlying these functions are the key to understand brains in general, but so far they are completely unknown. Three problems have hindered progress: 1) The animal’s desired state of the world is rarely known. 2) Most studies in simple models have focused on sensory driven, reflex-like processes, and not considered self-initiated behavior. 3) The circuits underlying complex behaviors in vertebrates are widely distributed, containing millions of neurons. With this proposal I aim at overcoming these problems using insects, whose tiny brains solve the same basic problems as our brains but with 100,000 times fewer cells. Moreover, the central complex, a single conserved brain region consisting of only a few thousand neurons, is crucial for sensory integration, motor control and state-dependent modulation, essentially being a ‘brain in the brain’. To simplify the problem further I will focus on navigation behavior. Here, the desired and actual states of the world are equal to the desired and current headings of the animal, with mismatches resulting in compensatory steering. I have previously shown how the central complex encodes the animal’s current heading. Now I will use behavioral training to generate animals with highly defined desired headings, and correlate neural activity with the animal’s ‘intentions’ and actions - at the level of identified neurons. To establish the involved conserved core circuitry valid across insects I will compare species with distinct lifestyles. Secondly, I will reveal how these circuits have evolved to account for each species’ unique ecology. The proposed work will provide a coherent framework to study key concepts of fundamental brain functions in unprecedented detail - using a single, conserved, but flexible neural circuit.
Summary
The core function of all brains is to compute the current state of the world, compare it to the desired state of the world and select motor programs that drive behavior minimizing any mismatch. The circuits underlying these functions are the key to understand brains in general, but so far they are completely unknown. Three problems have hindered progress: 1) The animal’s desired state of the world is rarely known. 2) Most studies in simple models have focused on sensory driven, reflex-like processes, and not considered self-initiated behavior. 3) The circuits underlying complex behaviors in vertebrates are widely distributed, containing millions of neurons. With this proposal I aim at overcoming these problems using insects, whose tiny brains solve the same basic problems as our brains but with 100,000 times fewer cells. Moreover, the central complex, a single conserved brain region consisting of only a few thousand neurons, is crucial for sensory integration, motor control and state-dependent modulation, essentially being a ‘brain in the brain’. To simplify the problem further I will focus on navigation behavior. Here, the desired and actual states of the world are equal to the desired and current headings of the animal, with mismatches resulting in compensatory steering. I have previously shown how the central complex encodes the animal’s current heading. Now I will use behavioral training to generate animals with highly defined desired headings, and correlate neural activity with the animal’s ‘intentions’ and actions - at the level of identified neurons. To establish the involved conserved core circuitry valid across insects I will compare species with distinct lifestyles. Secondly, I will reveal how these circuits have evolved to account for each species’ unique ecology. The proposed work will provide a coherent framework to study key concepts of fundamental brain functions in unprecedented detail - using a single, conserved, but flexible neural circuit.
Max ERC Funding
1 500 000 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym BUCOPHSYS
Project Bottom-up hybrid control and planning synthesis with application to multi-robot multi-human coordination
Researcher (PI) DIMOS Dimarogonas
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Starting Grant (StG), PE7, ERC-2014-STG
Summary Current control applications necessitate the treatment of systems with multiple interconnected components, rather than the traditional single component paradigm that has been studied extensively. The individual subsystems may need to fulfil different and possibly conflicting specifications in a real-time manner. At the same time, they may need to fulfill coupled constraints that are defined as relations between their states. Towards this end, the need for methods for decentralized control at the continuous level and planning at the task level becomes apparent. We aim here towards unification of these two complementary approaches. Existing solutions rely on a top down centralized approach. We instead consider here a decentralized, bottom-up solution to the problem. The approach relies on three layers of interaction. In the first layer, agents aim at coordinating in order to fulfil their coupled constraints with limited communication exchange of their state information and design of appropriate feedback controllers; in the second layer, agents coordinate in order to mutually satisfy their discrete tasks through exchange of the corresponding plans in the form of automata; in the third and most challenging layer, the communication exchange for coordination now includes both continuous state and discrete plan/abstraction information. The results will be demonstrated in a scenario involving multiple (possibly human) users and multiple robots.
The unification will yield a completely decentralized system, in which the bottom up approach to define tasks, the consideration of coupled constraints and their combination towards distributed hybrid control and planning in a coordinated fashion require for
new ways of thinking and approaches to analysis and constitute the proposal a beyond the SoA and groundbreaking approach to the fields of control and computer science.
Summary
Current control applications necessitate the treatment of systems with multiple interconnected components, rather than the traditional single component paradigm that has been studied extensively. The individual subsystems may need to fulfil different and possibly conflicting specifications in a real-time manner. At the same time, they may need to fulfill coupled constraints that are defined as relations between their states. Towards this end, the need for methods for decentralized control at the continuous level and planning at the task level becomes apparent. We aim here towards unification of these two complementary approaches. Existing solutions rely on a top down centralized approach. We instead consider here a decentralized, bottom-up solution to the problem. The approach relies on three layers of interaction. In the first layer, agents aim at coordinating in order to fulfil their coupled constraints with limited communication exchange of their state information and design of appropriate feedback controllers; in the second layer, agents coordinate in order to mutually satisfy their discrete tasks through exchange of the corresponding plans in the form of automata; in the third and most challenging layer, the communication exchange for coordination now includes both continuous state and discrete plan/abstraction information. The results will be demonstrated in a scenario involving multiple (possibly human) users and multiple robots.
The unification will yield a completely decentralized system, in which the bottom up approach to define tasks, the consideration of coupled constraints and their combination towards distributed hybrid control and planning in a coordinated fashion require for
new ways of thinking and approaches to analysis and constitute the proposal a beyond the SoA and groundbreaking approach to the fields of control and computer science.
Max ERC Funding
1 498 729 €
Duration
Start date: 2015-03-01, End date: 2020-02-29
Project acronym C4T
Project Climate change across Cenozoic cooling steps reconstructed with clumped isotope thermometry
Researcher (PI) Anna Nele Meckler
Host Institution (HI) UNIVERSITETET I BERGEN
Call Details Starting Grant (StG), PE10, ERC-2014-STG
Summary The Earth's climate system contains a highly complex interplay of numerous components, such as atmospheric greenhouse gases, ice sheets, and ocean circulation. Due to nonlinearities and feedbacks, changes to the system can result in rapid transitions to radically different climate states. In light of rising greenhouse gas levels there is an urgent need to better understand climate at such tipping points. Reconstructions of profound climate changes in the past provide crucial insight into our climate system and help to predict future changes. However, all proxies we use to reconstruct past climate depend on assumptions that are in addition increasingly uncertain back in time. A new kind of temperature proxy, the carbonate ‘clumped isotope’ thermometer, has great potential to overcome these obstacles. The proxy relies on thermodynamic principles, taking advantage of the temperature-dependence of the binding strength between different isotopes of carbon and oxygen, which makes it independent of other variables. Yet, widespread application of this technique in paleoceanography is currently prevented by the required large sample amounts, which are difficult to obtain from ocean sediments. If applied to the minute carbonate shells preserved in the sediments, this proxy would allow robust reconstructions of past temperatures in the surface and deep ocean, as well as global ice volume, far back in time. Here I propose to considerably decrease sample amount requirements of clumped isotope thermometry, building on recent successful modifications of the method and ideas for further analytical improvements. This will enable my group and me to thoroughly ground-truth the proxy for application in paleoceanography and for the first time apply it to aspects of past climate change across major climate transitions in the past, where clumped isotope thermometry can immediately contribute to solving long-standing first-order questions and allow for major progress in the field.
Summary
The Earth's climate system contains a highly complex interplay of numerous components, such as atmospheric greenhouse gases, ice sheets, and ocean circulation. Due to nonlinearities and feedbacks, changes to the system can result in rapid transitions to radically different climate states. In light of rising greenhouse gas levels there is an urgent need to better understand climate at such tipping points. Reconstructions of profound climate changes in the past provide crucial insight into our climate system and help to predict future changes. However, all proxies we use to reconstruct past climate depend on assumptions that are in addition increasingly uncertain back in time. A new kind of temperature proxy, the carbonate ‘clumped isotope’ thermometer, has great potential to overcome these obstacles. The proxy relies on thermodynamic principles, taking advantage of the temperature-dependence of the binding strength between different isotopes of carbon and oxygen, which makes it independent of other variables. Yet, widespread application of this technique in paleoceanography is currently prevented by the required large sample amounts, which are difficult to obtain from ocean sediments. If applied to the minute carbonate shells preserved in the sediments, this proxy would allow robust reconstructions of past temperatures in the surface and deep ocean, as well as global ice volume, far back in time. Here I propose to considerably decrease sample amount requirements of clumped isotope thermometry, building on recent successful modifications of the method and ideas for further analytical improvements. This will enable my group and me to thoroughly ground-truth the proxy for application in paleoceanography and for the first time apply it to aspects of past climate change across major climate transitions in the past, where clumped isotope thermometry can immediately contribute to solving long-standing first-order questions and allow for major progress in the field.
Max ERC Funding
1 877 209 €
Duration
Start date: 2015-08-01, End date: 2020-07-31
Project acronym CHEMOSENSORYCIRCUITS
Project Function of Chemosensory Circuits
Researcher (PI) Emre Yaksi
Host Institution (HI) NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU
Call Details Starting Grant (StG), LS5, ERC-2013-StG
Summary Smell and taste are the least studied of all senses. Very little is known about chemosensory information processing beyond the level of receptor neurons. Every morning we enjoy our coffee thanks to our brains ability to combine and process multiple sensory modalities. Meanwhile, we can still review a document on our desk by adjusting the weights of numerous sensory inputs that constantly bombard our brains. Yet, the smell of our coffee may remind us that pleasant weekend breakfast through associative learning and memory. In the proposed project we will explore the function and the architecture of neural circuits that are involved in olfactory and gustatory information processing, namely habenula and brainstem. Moreover we will investigate the fundamental principles underlying multimodal sensory integration and the neural basis of behavior in these highly conserved brain areas.
To achieve these goals we will take an innovative approach by combining two-photon calcium imaging, optogenetics and electrophysiology with the expanding genetic toolbox of a small vertebrate, the zebrafish. This pioneering approach will enable us to design new types of experiments that were unthinkable only a few years ago. Using this unique combination of methods, we will monitor and perturb the activity of functionally distinct elements of habenular and brainstem circuits, in vivo. The habenula and brainstem are important in mediating stress/anxiety and eating habits respectively. Therefore, understanding the neural computations in these brain regions is important for comprehending the neural mechanisms underlying psychological conditions related to anxiety and eating disorders. We anticipate that our results will go beyond chemical senses and contribute new insights to the understanding of how brain circuits work and interact with the sensory world to shape neural activity and behavioral outputs of animals.
Summary
Smell and taste are the least studied of all senses. Very little is known about chemosensory information processing beyond the level of receptor neurons. Every morning we enjoy our coffee thanks to our brains ability to combine and process multiple sensory modalities. Meanwhile, we can still review a document on our desk by adjusting the weights of numerous sensory inputs that constantly bombard our brains. Yet, the smell of our coffee may remind us that pleasant weekend breakfast through associative learning and memory. In the proposed project we will explore the function and the architecture of neural circuits that are involved in olfactory and gustatory information processing, namely habenula and brainstem. Moreover we will investigate the fundamental principles underlying multimodal sensory integration and the neural basis of behavior in these highly conserved brain areas.
To achieve these goals we will take an innovative approach by combining two-photon calcium imaging, optogenetics and electrophysiology with the expanding genetic toolbox of a small vertebrate, the zebrafish. This pioneering approach will enable us to design new types of experiments that were unthinkable only a few years ago. Using this unique combination of methods, we will monitor and perturb the activity of functionally distinct elements of habenular and brainstem circuits, in vivo. The habenula and brainstem are important in mediating stress/anxiety and eating habits respectively. Therefore, understanding the neural computations in these brain regions is important for comprehending the neural mechanisms underlying psychological conditions related to anxiety and eating disorders. We anticipate that our results will go beyond chemical senses and contribute new insights to the understanding of how brain circuits work and interact with the sensory world to shape neural activity and behavioral outputs of animals.
Max ERC Funding
1 499 471 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym COGOPTO
Project The role of parvalbumin interneurons in cognition and behavior
Researcher (PI) Eva Marie Carlen
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS5, ERC-2013-StG
Summary Cognition is a collective term for complex but sophisticated mental processes such as attention, learning, social interaction, language production, decision making and other executive functions. For normal brain function, these higher-order functions need to be aptly regulated and controlled, and the physiology and cellular substrates for cognitive functions are under intense investigation. The loss of cognitive control is intricately related to pathological states such as schizophrenia, depression, attention deficit hyperactive disorder and addiction.
Synchronized neural activity can be observed when the brain performs several important functions, including cognitive processes. As an example, gamma activity (30-80 Hz) predicts the allocation of attention and theta activity (4-12 Hz) is tightly linked to memory processes. A large body of work indicates that the integrity of local and global neural synchrony is mediated by interneuron networks and actuated by the balance of different neuromodulators.
However, much knowledge is still needed on the functional role interneurons play in cognitive processes, i.e. how the interneurons contribute to local and global network processes subserving cognition, and ultimately play a role in behavior. In addition, we need to understand how neuro-modulators, such as dopamine, regulate interneuron function.
The proposed project aims to functionally determine the specific role the parvalbumin interneurons and the neuromodulator dopamine in aspects of cognition, and in behavior. In addition, we ask the question if cognition can be enhanced.
We are employing a true multidisciplinary approach where brain activity is recorded in conjunctions with optogenetic manipulations of parvalbumin interneurons in animals performing cognitive tasks. In one set of experiments knock-down of dopamine receptors specifically in parvalbumin interneurons is employed to probe how this neuromodulator regulate network functions.
Summary
Cognition is a collective term for complex but sophisticated mental processes such as attention, learning, social interaction, language production, decision making and other executive functions. For normal brain function, these higher-order functions need to be aptly regulated and controlled, and the physiology and cellular substrates for cognitive functions are under intense investigation. The loss of cognitive control is intricately related to pathological states such as schizophrenia, depression, attention deficit hyperactive disorder and addiction.
Synchronized neural activity can be observed when the brain performs several important functions, including cognitive processes. As an example, gamma activity (30-80 Hz) predicts the allocation of attention and theta activity (4-12 Hz) is tightly linked to memory processes. A large body of work indicates that the integrity of local and global neural synchrony is mediated by interneuron networks and actuated by the balance of different neuromodulators.
However, much knowledge is still needed on the functional role interneurons play in cognitive processes, i.e. how the interneurons contribute to local and global network processes subserving cognition, and ultimately play a role in behavior. In addition, we need to understand how neuro-modulators, such as dopamine, regulate interneuron function.
The proposed project aims to functionally determine the specific role the parvalbumin interneurons and the neuromodulator dopamine in aspects of cognition, and in behavior. In addition, we ask the question if cognition can be enhanced.
We are employing a true multidisciplinary approach where brain activity is recorded in conjunctions with optogenetic manipulations of parvalbumin interneurons in animals performing cognitive tasks. In one set of experiments knock-down of dopamine receptors specifically in parvalbumin interneurons is employed to probe how this neuromodulator regulate network functions.
Max ERC Funding
1 400 000 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym COOPNET
Project Cooperative Situational Awareness for Wireless Networks
Researcher (PI) Henk Wymeersch
Host Institution (HI) CHALMERS TEKNISKA HOEGSKOLA AB
Call Details Starting Grant (StG), PE7, ERC-2010-StG_20091028
Summary Devices in wireless networks are no longer used only for communicating binary information, but also for navigation and to sense their surroundings. We are currently approaching fundamental limitations in terms of communication throughput, position information availability and accuracy, and decision making based on sensory data. The goal of this proposal is to understand how the cooperative nature of future wireless networks can be leveraged to perform timekeeping, positioning, communication, and decision making, so as to obtain orders of magnitude performance improvements compared to current architectures.
Our research will have implications in many fields and will comprise fundamental theoretical contributions as well as a cooperative wireless testbed. The fundamental contributions will lead to a deep understanding of cooperative wireless networks and will enable new pervasive applications which currently cannot be supported. The testbed will be used to validate the research, and will serve as a kernel for other researchers worldwide to advance knowledge on cooperative networks. Our work will build on and consolidate knowledge currently dispersed in different scientific disciplines and communities (such as communication theory, sensor networks, distributed estimation and detection, environmental monitoring, control theory, positioning and timekeeping, distributed optimization). It will give a new thrust to research within those communities and forge relations between them.
Summary
Devices in wireless networks are no longer used only for communicating binary information, but also for navigation and to sense their surroundings. We are currently approaching fundamental limitations in terms of communication throughput, position information availability and accuracy, and decision making based on sensory data. The goal of this proposal is to understand how the cooperative nature of future wireless networks can be leveraged to perform timekeeping, positioning, communication, and decision making, so as to obtain orders of magnitude performance improvements compared to current architectures.
Our research will have implications in many fields and will comprise fundamental theoretical contributions as well as a cooperative wireless testbed. The fundamental contributions will lead to a deep understanding of cooperative wireless networks and will enable new pervasive applications which currently cannot be supported. The testbed will be used to validate the research, and will serve as a kernel for other researchers worldwide to advance knowledge on cooperative networks. Our work will build on and consolidate knowledge currently dispersed in different scientific disciplines and communities (such as communication theory, sensor networks, distributed estimation and detection, environmental monitoring, control theory, positioning and timekeeping, distributed optimization). It will give a new thrust to research within those communities and forge relations between them.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
Project acronym ENDOSWITCH
Project Network Principles of Neuroendocrine Control:
Tuberoinfundibular Dopamine (TIDA) Oscillations and the Regulation of Lactation
Researcher (PI) Carl Christian Broberger
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS5, ERC-2010-StG_20091118
Summary The hypothalamus is essential for our survival and orchestrates every vital function of the body, from defence against predators and energy metabolism to reproduction. Yet, the network mechanisms underlying these actions remain largely hidden in a black box . Here, we will focus on the hypothalamic neuroendocrine system, where we have identified a novel robust network oscillation in the tuberoinfundibular dopamine (TIDA) neurons that control prolactin release. This oscillation is synchronized between neurons via gap junctions, and phasic firing is transformed into tonic discharge by compounds that functionally oppose neuroendocrine dopamine actions. Using this novel preparation, we will investigate the 1) the cellular (conductance) and network (connectivity) mechanisms underlying TIDA rhythmicity; 2) how TIDA activity is affected by hormones and transmitters that affect lactation; 3) the functional significance of phasic vs. tonic discharge in the regulation of dopamine release and lactation; and 4) the generality of TIDA cellular and network properties to other parvocellular neuron populations. These questions will be addressed through several in vitro and in vivo electrophysiological techniques, including slice whole-cell recording, extracellular in vivo recording, voltammetry and optical recording. These experiments will provide novel insight into the link between network interactions and behaviour, and have important clinical implications for e.g. endocrine and reproductive disorders.
Summary
The hypothalamus is essential for our survival and orchestrates every vital function of the body, from defence against predators and energy metabolism to reproduction. Yet, the network mechanisms underlying these actions remain largely hidden in a black box . Here, we will focus on the hypothalamic neuroendocrine system, where we have identified a novel robust network oscillation in the tuberoinfundibular dopamine (TIDA) neurons that control prolactin release. This oscillation is synchronized between neurons via gap junctions, and phasic firing is transformed into tonic discharge by compounds that functionally oppose neuroendocrine dopamine actions. Using this novel preparation, we will investigate the 1) the cellular (conductance) and network (connectivity) mechanisms underlying TIDA rhythmicity; 2) how TIDA activity is affected by hormones and transmitters that affect lactation; 3) the functional significance of phasic vs. tonic discharge in the regulation of dopamine release and lactation; and 4) the generality of TIDA cellular and network properties to other parvocellular neuron populations. These questions will be addressed through several in vitro and in vivo electrophysiological techniques, including slice whole-cell recording, extracellular in vivo recording, voltammetry and optical recording. These experiments will provide novel insight into the link between network interactions and behaviour, and have important clinical implications for e.g. endocrine and reproductive disorders.
Max ERC Funding
1 493 958 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym FSA
Project Fluid Spectrum Acess
Researcher (PI) Alexandre Proutiere
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Starting Grant (StG), PE7, ERC-2012-StG_20111012
Summary Spectrum is a key and scarce resource in wireless communication networks, and it remains tightly controlled by regulation authorities. Most of the frequency bands are exclusively allocated to a single system licensed to use it everywhere and for long periods of time. This rigid spectrum management model inevitably leads to significant inefficiencies in spectrum use. The explosion of demand for broadband wireless services also calls for more flexible models where much larger spectrum parts could be dynamically shared among users in a fluid manner. In such models, Dynamic Spectrum Access (DSA) techniques will play a major role. These techniques make it possible for radio devices to become frequency-agile, i.e. able to rapidly and dynamically access bands of a wide spectrum part.
The success and spread of dynamic spectrum access strongly rely on the ability for many frequency-agile devices (or systems) to coexist peacefully and efficiently. With multiple interacting devices, the research agenda shifts from spectrum access problems to spectrum sharing problems, which raises original and challenging questions. There may be limited or no communication between the different devices or systems sharing spectrum. We further expect systems to be heterogeneous in their transmission capabilities, but also in the type of service they support. In that context, the design of spectrum access strategies resulting in an efficient and fair spectrum resource use constitutes a challenging puzzle. The broad objective of the proposed research is to develop original analytical and simulation tools to tackle dynamic spectrum sharing issues. The project leverages and marries techniques from distributed optimization and machine learning to design decentralized, efficient, and fair spectrum sharing algorithms. We believe that such algorithms are critical for the birth and rapid expansion of DSA technologies and hence for the development of future wireless broadband systems.
Summary
Spectrum is a key and scarce resource in wireless communication networks, and it remains tightly controlled by regulation authorities. Most of the frequency bands are exclusively allocated to a single system licensed to use it everywhere and for long periods of time. This rigid spectrum management model inevitably leads to significant inefficiencies in spectrum use. The explosion of demand for broadband wireless services also calls for more flexible models where much larger spectrum parts could be dynamically shared among users in a fluid manner. In such models, Dynamic Spectrum Access (DSA) techniques will play a major role. These techniques make it possible for radio devices to become frequency-agile, i.e. able to rapidly and dynamically access bands of a wide spectrum part.
The success and spread of dynamic spectrum access strongly rely on the ability for many frequency-agile devices (or systems) to coexist peacefully and efficiently. With multiple interacting devices, the research agenda shifts from spectrum access problems to spectrum sharing problems, which raises original and challenging questions. There may be limited or no communication between the different devices or systems sharing spectrum. We further expect systems to be heterogeneous in their transmission capabilities, but also in the type of service they support. In that context, the design of spectrum access strategies resulting in an efficient and fair spectrum resource use constitutes a challenging puzzle. The broad objective of the proposed research is to develop original analytical and simulation tools to tackle dynamic spectrum sharing issues. The project leverages and marries techniques from distributed optimization and machine learning to design decentralized, efficient, and fair spectrum sharing algorithms. We believe that such algorithms are critical for the birth and rapid expansion of DSA technologies and hence for the development of future wireless broadband systems.
Max ERC Funding
1 197 040 €
Duration
Start date: 2012-11-01, End date: 2017-10-31
Project acronym HYDROCARB
Project Towards a new understanding of carbon processing in freshwaters: methane emission hot spots and carbon burial
Researcher (PI) Sebastian Sobek
Host Institution (HI) UPPSALA UNIVERSITET
Call Details Starting Grant (StG), PE10, ERC-2013-StG
Summary In spite of their small areal extent, inland waters play a vital role in the carbon cycle of the continents, as they emit significant amounts of the greenhouse gases (GHG) carbon dioxide (CO2) and methane (CH4) to the atmosphere, and simultaneously bury more organic carbon (OC) in their sediments than the entire ocean. Particularly in tropical hydropower reservoirs, GHG emissions can be large, mainly owing to high CH4 emission. Moreover, the number of tropical hydropower reservoirs will continue to increase dramatically, due to an urgent need for economic growth and a vast unused hydropower potential in many tropical countries. However, the current understanding of the magnitude of GHG emission, and of the processes regulating it, is insufficient. Here I propose a research program on tropical reservoirs in Brazil that takes advantage of recent developments in both concepts and methodologies to provide unique evaluations of GHG emission and OC burial in tropical reservoirs. In particular, I will test the following hypotheses: 1) Current estimates of reservoir CH4 emission are at least one order of magnitude too low, since they have completely missed the recently discovered existence of gas bubble emission hot spots; 2) The burial of land-derived OC in reservoir sediments offsets a significant share of the GHG emissions; and 3) The sustained, long-term CH4 emission from reservoirs is to a large degree fuelled by primary production of new OC within the reservoir, and may therefore be reduced by management of nutrient supply. The new understanding and the cross-disciplinary methodological approach will constitute a major advance to aquatic science in general, and have strong impacts on the understanding of other aquatic systems at other latitudes as well. In addition, the results will be merged into an existing reservoir GHG risk assessment tool to improve planning, design, management and judgment of hydropower reservoirs.
Summary
In spite of their small areal extent, inland waters play a vital role in the carbon cycle of the continents, as they emit significant amounts of the greenhouse gases (GHG) carbon dioxide (CO2) and methane (CH4) to the atmosphere, and simultaneously bury more organic carbon (OC) in their sediments than the entire ocean. Particularly in tropical hydropower reservoirs, GHG emissions can be large, mainly owing to high CH4 emission. Moreover, the number of tropical hydropower reservoirs will continue to increase dramatically, due to an urgent need for economic growth and a vast unused hydropower potential in many tropical countries. However, the current understanding of the magnitude of GHG emission, and of the processes regulating it, is insufficient. Here I propose a research program on tropical reservoirs in Brazil that takes advantage of recent developments in both concepts and methodologies to provide unique evaluations of GHG emission and OC burial in tropical reservoirs. In particular, I will test the following hypotheses: 1) Current estimates of reservoir CH4 emission are at least one order of magnitude too low, since they have completely missed the recently discovered existence of gas bubble emission hot spots; 2) The burial of land-derived OC in reservoir sediments offsets a significant share of the GHG emissions; and 3) The sustained, long-term CH4 emission from reservoirs is to a large degree fuelled by primary production of new OC within the reservoir, and may therefore be reduced by management of nutrient supply. The new understanding and the cross-disciplinary methodological approach will constitute a major advance to aquatic science in general, and have strong impacts on the understanding of other aquatic systems at other latitudes as well. In addition, the results will be merged into an existing reservoir GHG risk assessment tool to improve planning, design, management and judgment of hydropower reservoirs.
Max ERC Funding
1 798 227 €
Duration
Start date: 2013-09-01, End date: 2019-08-31
Project acronym iGLURs - A NEW VIEW
Project Exposing nature’s view of ligand recognition in ionotropic glutamate receptors
Researcher (PI) Timothy Peter Lynagh
Host Institution (HI) UNIVERSITETET I BERGEN
Call Details Starting Grant (StG), LS5, ERC-2018-STG
Summary Molecular biology strives for the prediction of function, based on the genetic code. Within neuroscience, this is reflected in the intense study of the molecular basis for ligand recognition by neurotransmitter receptors. Consequently, structural and functional studies have rendered a profoundly high-resolution view of ionotropic glutamate receptors (iGluRs), the archetypal excitatory receptor in the brain. But even this view is obsolete: we don’t know why some receptors recognize glutamate yet others recognize other ligands; and we have been unable to functionally test the underlying chemical interactions. In other words, our view differs substantially from nature’s own view of ligand recognition. I plan to lead a workgroup attacking this problem on three fronts. First, bioinformatic identification and electrophysiological characterization of a broad and representative sample of iGluRs from across the spectrum of life will unveil the diversity of ligand recognition in iGluRs. Second, phylogenetic analyses combined with functional experiments will reveal the molecular changes that nature employed in arriving at existing means of ligand recognition in iGluRs. Finally, chemical-scale mutagenesis will be employed to overcome previous technical limitations and dissect the precise chemical interactions that determine the specific recognition of certain ligands. With my experience in combining phylogenetics and functional experiments and in the use of chemical-scale mutagenesis, the objectives are within reach. Together, they form a unique approach that will expose nature’s own view of ligand recognition in iGluRs, revealing the molecular blueprint for protein function in the nervous system.
Summary
Molecular biology strives for the prediction of function, based on the genetic code. Within neuroscience, this is reflected in the intense study of the molecular basis for ligand recognition by neurotransmitter receptors. Consequently, structural and functional studies have rendered a profoundly high-resolution view of ionotropic glutamate receptors (iGluRs), the archetypal excitatory receptor in the brain. But even this view is obsolete: we don’t know why some receptors recognize glutamate yet others recognize other ligands; and we have been unable to functionally test the underlying chemical interactions. In other words, our view differs substantially from nature’s own view of ligand recognition. I plan to lead a workgroup attacking this problem on three fronts. First, bioinformatic identification and electrophysiological characterization of a broad and representative sample of iGluRs from across the spectrum of life will unveil the diversity of ligand recognition in iGluRs. Second, phylogenetic analyses combined with functional experiments will reveal the molecular changes that nature employed in arriving at existing means of ligand recognition in iGluRs. Finally, chemical-scale mutagenesis will be employed to overcome previous technical limitations and dissect the precise chemical interactions that determine the specific recognition of certain ligands. With my experience in combining phylogenetics and functional experiments and in the use of chemical-scale mutagenesis, the objectives are within reach. Together, they form a unique approach that will expose nature’s own view of ligand recognition in iGluRs, revealing the molecular blueprint for protein function in the nervous system.
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym IN-BRAIN
Project IN VIVO REPROGRAMMING: A NOVEL ROUTE TO BRAIN REPAIR
Researcher (PI) Malin Parmar
Host Institution (HI) LUNDS UNIVERSITET
Call Details Starting Grant (StG), LS5, ERC-2012-StG_20111109
Summary Recent progress on direct re-programming into functional neurons provides a new approach towards cell-based therapy for neurodegenerative disorders. The induced neurons (iNs) are a novel type of cell resulting from rapid and remarkable conversion of somatic cells into subtype-specific functional neurons. Importantly they are non-proliferating which make them interesting alternatives to induced pluripotent (iPS) cells as sources of patient specific neurons for exogenous cell replacement therapy and disease modeling.
Another major advantage with direct conversion over iPS cells is that the reprogramming could be performed in vivo. While direct conversion has been successful in organs such as the pancreas, where exocrine cells can be directly converted into insulin producing cells by viral injections in vivo (Zhou et al., Nature, 2008), the method is yet to be explored in the brain. Once direct conversion of non-neuronal cells into subtype specific neurons directly in the brain is established, it provides a new strategy for cell based brain repair that do not depend on exogenous cells.
The overall goal of this project is to provide proof-of-principle that induced neurogenesis is achievable in the adult brain through guided transcription factor reprogramming of non-neuronal cells, to determine which cells are best suited as cellular substrate for in vivo neural conversion, and to compare this approach with transplantation of converted fibroblasts.
The ability to directly reprogram cell fate using defined combinations of transcription factors have already turned basic studies of stem cell differentiation and cell therapy into a new direction. Establishing this technique in vivo would be another paradigm-shifting finding that opens up for novel strategies for brain repair
Summary
Recent progress on direct re-programming into functional neurons provides a new approach towards cell-based therapy for neurodegenerative disorders. The induced neurons (iNs) are a novel type of cell resulting from rapid and remarkable conversion of somatic cells into subtype-specific functional neurons. Importantly they are non-proliferating which make them interesting alternatives to induced pluripotent (iPS) cells as sources of patient specific neurons for exogenous cell replacement therapy and disease modeling.
Another major advantage with direct conversion over iPS cells is that the reprogramming could be performed in vivo. While direct conversion has been successful in organs such as the pancreas, where exocrine cells can be directly converted into insulin producing cells by viral injections in vivo (Zhou et al., Nature, 2008), the method is yet to be explored in the brain. Once direct conversion of non-neuronal cells into subtype specific neurons directly in the brain is established, it provides a new strategy for cell based brain repair that do not depend on exogenous cells.
The overall goal of this project is to provide proof-of-principle that induced neurogenesis is achievable in the adult brain through guided transcription factor reprogramming of non-neuronal cells, to determine which cells are best suited as cellular substrate for in vivo neural conversion, and to compare this approach with transplantation of converted fibroblasts.
The ability to directly reprogram cell fate using defined combinations of transcription factors have already turned basic studies of stem cell differentiation and cell therapy into a new direction. Establishing this technique in vivo would be another paradigm-shifting finding that opens up for novel strategies for brain repair
Max ERC Funding
1 500 000 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym LUSI LAB
Project Lusi: a unique natural laboratory for multidisciplinary studies of focussed fluid flow in sedimentary basins
Researcher (PI) Adriano Mazzini
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Starting Grant (StG), PE10, ERC-2012-StG_20111012
Summary The 29th of May 2006 several gas and mud eruption sites suddenly appeared along a fault in the NE of Java, Indonesia. Within weeks several villages were submerged by boiling mud. The most prominent eruption site was named Lusi. To date Lusi is still active and has forced 50.000 people to be evacuated and an area of more than 7 km2 is covered by mud. The social impact of the eruption and its spectacular dimensions still attract the attention of international media. Since 2006 I have completed four expeditions to Indonesia and initiated quantitative and experimental studies leading to the publication of two papers focussing on the plumbing system and the mechanisms of the Lusi eruption. However still many unanswered questions remain. What lies beneath Lusi? Is Lusi a mud volcano or part of a larger hydrothermal system? What are the mechanisms triggering the eruption? How long will the eruption last?
LUSI LAB is an ambitious project that aims to answer these questions and to perform a multidisciplinary study using Lusi as a unique natural laboratory. Due to its relatively easy accessibility, the geological setting, and the vast scale, the Lusi eruption represents an unprecedented opportunity to study and learn from an ongoing active eruptive system. The results will be crucial for understanding focused fluid flow systems in other sedimentary basins world-wide, and to unravel issues related to geohazards and palaeoclimate aspects. The project will use multisensory sampling devices within the active feeder channel and a remote-controlled raft and flying device to access and sample the crater and the erupted gases. UV-gas camera imaging to measure the rate and composition of the erupted gases will be coupled with a network of seismometers to evaluate the impact that seismicity, local faulting and the neighbouring Arjuno-Welirang volcanic complex have on the long-lasting Lusi activity. This information will provide robust constraints to model the pulsating Lusi behaviour.
Summary
The 29th of May 2006 several gas and mud eruption sites suddenly appeared along a fault in the NE of Java, Indonesia. Within weeks several villages were submerged by boiling mud. The most prominent eruption site was named Lusi. To date Lusi is still active and has forced 50.000 people to be evacuated and an area of more than 7 km2 is covered by mud. The social impact of the eruption and its spectacular dimensions still attract the attention of international media. Since 2006 I have completed four expeditions to Indonesia and initiated quantitative and experimental studies leading to the publication of two papers focussing on the plumbing system and the mechanisms of the Lusi eruption. However still many unanswered questions remain. What lies beneath Lusi? Is Lusi a mud volcano or part of a larger hydrothermal system? What are the mechanisms triggering the eruption? How long will the eruption last?
LUSI LAB is an ambitious project that aims to answer these questions and to perform a multidisciplinary study using Lusi as a unique natural laboratory. Due to its relatively easy accessibility, the geological setting, and the vast scale, the Lusi eruption represents an unprecedented opportunity to study and learn from an ongoing active eruptive system. The results will be crucial for understanding focused fluid flow systems in other sedimentary basins world-wide, and to unravel issues related to geohazards and palaeoclimate aspects. The project will use multisensory sampling devices within the active feeder channel and a remote-controlled raft and flying device to access and sample the crater and the erupted gases. UV-gas camera imaging to measure the rate and composition of the erupted gases will be coupled with a network of seismometers to evaluate the impact that seismicity, local faulting and the neighbouring Arjuno-Welirang volcanic complex have on the long-lasting Lusi activity. This information will provide robust constraints to model the pulsating Lusi behaviour.
Max ERC Funding
1 422 420 €
Duration
Start date: 2013-01-01, End date: 2018-12-31
Project acronym M&M´S
Project New Paradigms for MEMS & NEMS Integration
Researcher (PI) Frank Niklaus
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Starting Grant (StG), PE7, ERC-2011-StG_20101014
Summary Micro- and nanoelectromechanical system (MEMS and NEMS) components are vital for many industrial and consumer products such as airbag systems in cars and motion controls in mobile phones, and many of these MEMS and NEMS enabled applications have a large impact on European industry and society. However, the potential of MEMS and NEMS is being critically hampered by their dependence on integrated circuit (IC) manufacturing technologies. Most micro- and nano-manufacturing methods have been developed by the IC industry and are characterized by highly standardized manufacturing processes that are adapted for extremely large production volumes of more than 10.000 wafers per month. In contrast, the vast majority of MEMS and NEMS applications only demands production volumes of less than 100 wafers per month in combination with different non-standardized manufacturing and integration processes for each product. If a much wider variety of diverse and even low-volume MEMS and NEMS products shall be exploited, the semiconductor manufacturing paradigm has to be broken. In this project, we therefore will focus on frontier research on new paradigms for flexible and cost-efficient manufacturing and integration of MEMS and NEMS within three related research areas:
(1) Wafer-Level Heterogeneous Integration for MEMS and NEMS, where we explore new and improved wafer-level heterogeneous integration technologies for MEMS and NEMS devices;
(2) Integration of Materials into MEMS Using High-Speed Wire Bonding Tools, where we explore new ways of integrating various types of wire materials into MEMS devices;
(3) Free-Form 3D Printing of Mono-Crystalline Silicon Micro- and Nanostructures, where we explore entirely novel ways of implementing mono-crystalline silicon MEMS and NEMS structures that can be arbitrarily shaped.
Summary
Micro- and nanoelectromechanical system (MEMS and NEMS) components are vital for many industrial and consumer products such as airbag systems in cars and motion controls in mobile phones, and many of these MEMS and NEMS enabled applications have a large impact on European industry and society. However, the potential of MEMS and NEMS is being critically hampered by their dependence on integrated circuit (IC) manufacturing technologies. Most micro- and nano-manufacturing methods have been developed by the IC industry and are characterized by highly standardized manufacturing processes that are adapted for extremely large production volumes of more than 10.000 wafers per month. In contrast, the vast majority of MEMS and NEMS applications only demands production volumes of less than 100 wafers per month in combination with different non-standardized manufacturing and integration processes for each product. If a much wider variety of diverse and even low-volume MEMS and NEMS products shall be exploited, the semiconductor manufacturing paradigm has to be broken. In this project, we therefore will focus on frontier research on new paradigms for flexible and cost-efficient manufacturing and integration of MEMS and NEMS within three related research areas:
(1) Wafer-Level Heterogeneous Integration for MEMS and NEMS, where we explore new and improved wafer-level heterogeneous integration technologies for MEMS and NEMS devices;
(2) Integration of Materials into MEMS Using High-Speed Wire Bonding Tools, where we explore new ways of integrating various types of wire materials into MEMS devices;
(3) Free-Form 3D Printing of Mono-Crystalline Silicon Micro- and Nanostructures, where we explore entirely novel ways of implementing mono-crystalline silicon MEMS and NEMS structures that can be arbitrarily shaped.
Max ERC Funding
1 495 982 €
Duration
Start date: 2011-11-01, End date: 2017-10-31
Project acronym MC2
Project Mixed-phase clouds and climate (MC2) – from process-level understanding to large-scale impacts
Researcher (PI) Trude STORELVMO
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Starting Grant (StG), PE10, ERC-2017-STG
Summary The importance of mixed-phase clouds (i.e. clouds in which liquid and ice may co-exist) for weather and climate has become increasingly evident in recent years. We now know that a majority of the precipitation reaching Earth’s surface originates from mixed-phase clouds, and the way cloud phase changes under global warming has emerged as a critically important climate feedback. Atmospheric aerosols may also have affected climate via mixed-phase clouds, but the magnitude and even sign of this effect is currently unknown. Satellite observations have recently revealed that cloud phase is misrepresented in global climate models (GCMs), suggesting systematic GCM biases in precipitation formation and cloud-climate feedbacks. Such biases give us reason to doubt GCM projections of the climate response to CO2 increases, or to changing atmospheric aerosol loadings. This proposal seeks to address the above issues, through a multi-angle and multi-tool approach: (i) By conducting field measurements of cloud phase at mid- and high latitudes, we seek to identify the small-scale structure of mixed-phase clouds. (ii) Large-eddy simulations will then be employed to identify the underlying physics responsible for the observed structures, and the field measurements will provide case studies for regional cloud-resolving modelling in order to test and revise state-of-the-art cloud microphysics parameterizations. (iii) GCMs, with revised microphysics parameterizations, will be confronted with cloud phase constraints available from space. (iv) Finally, the same GCMs will be used to re-evaluate the climate impact of mixed-phase clouds in terms of their contribution to climate forcings and feedbacks. Through this synergistic combination of tools for a multi-scale study of mixed-phase clouds, the proposed research has the potential to bring the field of climate science forward, from improved process-level understanding at small scales, to better climate change predictions on the global scale.
Summary
The importance of mixed-phase clouds (i.e. clouds in which liquid and ice may co-exist) for weather and climate has become increasingly evident in recent years. We now know that a majority of the precipitation reaching Earth’s surface originates from mixed-phase clouds, and the way cloud phase changes under global warming has emerged as a critically important climate feedback. Atmospheric aerosols may also have affected climate via mixed-phase clouds, but the magnitude and even sign of this effect is currently unknown. Satellite observations have recently revealed that cloud phase is misrepresented in global climate models (GCMs), suggesting systematic GCM biases in precipitation formation and cloud-climate feedbacks. Such biases give us reason to doubt GCM projections of the climate response to CO2 increases, or to changing atmospheric aerosol loadings. This proposal seeks to address the above issues, through a multi-angle and multi-tool approach: (i) By conducting field measurements of cloud phase at mid- and high latitudes, we seek to identify the small-scale structure of mixed-phase clouds. (ii) Large-eddy simulations will then be employed to identify the underlying physics responsible for the observed structures, and the field measurements will provide case studies for regional cloud-resolving modelling in order to test and revise state-of-the-art cloud microphysics parameterizations. (iii) GCMs, with revised microphysics parameterizations, will be confronted with cloud phase constraints available from space. (iv) Finally, the same GCMs will be used to re-evaluate the climate impact of mixed-phase clouds in terms of their contribution to climate forcings and feedbacks. Through this synergistic combination of tools for a multi-scale study of mixed-phase clouds, the proposed research has the potential to bring the field of climate science forward, from improved process-level understanding at small scales, to better climate change predictions on the global scale.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym MoNaLISA
Project Long-term molecular nanoscale imaging of neuronal function
Researcher (PI) Ilaria Testa
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary Synaptic function is difficult to analyze in living neurons using conventional optics, since the synaptic organelles and protein clusters are small and tightly spaced. The solution to this problem can come from the field of super-resolution fluorescence microscopy, or nanoscopy. However, the current approaches to nanoscopy are still far from reaching this goal. Single molecule-based approaches (including STORM and PALM) provide high spatial resolution, but slow recording, insufficient for live imaging. Ensemble approaches (including SSIM and STED) are able to record faster, but with poorer resolution or with high, potentially toxic, laser powers. It is currently impossible to image the same neuron for hours and days, with both high spatial (~30 nm) and temporal (10-1000 Hz) resolution, and with minimal photodamage. My aim is to fill this gap, by developing, for the first time, a microscope that combines the advantages of both single molecule-based and ensemble approaches. I will base the microscope on RESOLFT, a low-photodamage ensemble approach that I have pioneered recently. I will use line patterns to speed up the recording and 2photon-switching for 3D ability. I will combine this with sensitive detection schemes that allow single-molecule detection and counting, relying on my previous expertise with PALM and GSDIM. The new set-up, termed molecular nanoscale long-term imaging with sequential acquisition (MoNaLISA), will track neuronal organelles and proteins on different time scales, spanning from milliseconds to days, with a resolution close to the molecular scale. To obtain the first proof-of-principle results, I will address several issues still open in the synaptic transmission field, relating to synaptic vesicle recycling, biogenesis and degradation. Overall, my project will introduce a novel paradigm to imaging in the life sciences, which will enable fast and quantitative nano-imaging of cells and tissues.
Summary
Synaptic function is difficult to analyze in living neurons using conventional optics, since the synaptic organelles and protein clusters are small and tightly spaced. The solution to this problem can come from the field of super-resolution fluorescence microscopy, or nanoscopy. However, the current approaches to nanoscopy are still far from reaching this goal. Single molecule-based approaches (including STORM and PALM) provide high spatial resolution, but slow recording, insufficient for live imaging. Ensemble approaches (including SSIM and STED) are able to record faster, but with poorer resolution or with high, potentially toxic, laser powers. It is currently impossible to image the same neuron for hours and days, with both high spatial (~30 nm) and temporal (10-1000 Hz) resolution, and with minimal photodamage. My aim is to fill this gap, by developing, for the first time, a microscope that combines the advantages of both single molecule-based and ensemble approaches. I will base the microscope on RESOLFT, a low-photodamage ensemble approach that I have pioneered recently. I will use line patterns to speed up the recording and 2photon-switching for 3D ability. I will combine this with sensitive detection schemes that allow single-molecule detection and counting, relying on my previous expertise with PALM and GSDIM. The new set-up, termed molecular nanoscale long-term imaging with sequential acquisition (MoNaLISA), will track neuronal organelles and proteins on different time scales, spanning from milliseconds to days, with a resolution close to the molecular scale. To obtain the first proof-of-principle results, I will address several issues still open in the synaptic transmission field, relating to synaptic vesicle recycling, biogenesis and degradation. Overall, my project will introduce a novel paradigm to imaging in the life sciences, which will enable fast and quantitative nano-imaging of cells and tissues.
Max ERC Funding
1 725 000 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym NANOSCOPY
Project High-speed chip-based nanoscopy to discover real-time sub-cellular dynamics
Researcher (PI) Balpreet Singh Ahluwalia
Host Institution (HI) UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET
Call Details Starting Grant (StG), PE7, ERC-2013-StG
Summary Optical nanoscopy has given a glimpse of the impact it may have on medical care in the future. Slow imaging speed and the complexity of the current nanoscope limits its use for living cells. The imaging speed is limited by the bulk optics that is used in present nanoscopy. In this project, I propose a paradigm-shift in the field of advanced microscopy by developing optical nanoscopy based on a photonic integrated circuit. The project will take advantage of nanotechnology to fabricate an advance waveguide-chip, while fast telecom optical devices will provide switching of light to the chip, enhancing the speed of imaging. This unconventional route will change the field of optical microscopy, as a simple chip-based system can be added to a normal microscope. In this project, I will build a waveguide-based structured-illumination microscope (W-SIM) to acquire fast images (25 Hz or better) from a living cell with an optical resolution of 50-100 nm. I will use W-SIM to discover the dynamics (opening and closing) of fenestrations (100 nm) present in the membrane of a living liver sinusoidal scavenger endothelial cell. It is believed among the Hepatology community that these fenestrations open and close dynamically, however there is no scientific evidence to support this hypothesis because of the lack of suitable tools. The successful imaging of fenestration kinetics in a live cell during this project will provide new fundamental knowledge and benefit human health with improved diagnoses and drug discovery for liver. Chip-based nanoscopy is a new research field, inherently making this a high-risk project, but the possible gains are also high. The W-SIM will be the first of its kind, which may open a new era of simple, integrated nanoscopy. The proposed multiple-disciplinary project requires a near-unique expertise in the field of laser physics, integrated optics, advanced microscopy and cell-biology that I have acquired at leading research centers on three continents.
Summary
Optical nanoscopy has given a glimpse of the impact it may have on medical care in the future. Slow imaging speed and the complexity of the current nanoscope limits its use for living cells. The imaging speed is limited by the bulk optics that is used in present nanoscopy. In this project, I propose a paradigm-shift in the field of advanced microscopy by developing optical nanoscopy based on a photonic integrated circuit. The project will take advantage of nanotechnology to fabricate an advance waveguide-chip, while fast telecom optical devices will provide switching of light to the chip, enhancing the speed of imaging. This unconventional route will change the field of optical microscopy, as a simple chip-based system can be added to a normal microscope. In this project, I will build a waveguide-based structured-illumination microscope (W-SIM) to acquire fast images (25 Hz or better) from a living cell with an optical resolution of 50-100 nm. I will use W-SIM to discover the dynamics (opening and closing) of fenestrations (100 nm) present in the membrane of a living liver sinusoidal scavenger endothelial cell. It is believed among the Hepatology community that these fenestrations open and close dynamically, however there is no scientific evidence to support this hypothesis because of the lack of suitable tools. The successful imaging of fenestration kinetics in a live cell during this project will provide new fundamental knowledge and benefit human health with improved diagnoses and drug discovery for liver. Chip-based nanoscopy is a new research field, inherently making this a high-risk project, but the possible gains are also high. The W-SIM will be the first of its kind, which may open a new era of simple, integrated nanoscopy. The proposed multiple-disciplinary project requires a near-unique expertise in the field of laser physics, integrated optics, advanced microscopy and cell-biology that I have acquired at leading research centers on three continents.
Max ERC Funding
1 490 976 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym PERICYTESCAR
Project The role of pericytes in central nervous system scarring and fibrosis
Researcher (PI) Christian Göritz
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS5, ERC-2012-StG_20111109
Summary Damage to the central nervous system (CNS) often leads to persistent functional deficits, causing
great individual suffering and enormous cost to society. The manifestation of these deficits is
believed to be associated with the scar tissue that forms locally at lesions, causing permanent tissue
alteration and blocking regeneration.
Research on CNS scar tissue has primarily focused on astrocytes and it is often referred to as the
glial scar. However, although it has received much less attention, there is also a connective tissue or
stromal, non-glial, component of the scar.
While studying spinal cord injury-induced scarring, I recently discovered a new subpopulation of
perivascular cells, named type A pericytes, as a major source of connective scar tissue. Type A
pericytes are embedded in the vascular wall but proliferate and leave the blood vessel upon injury,
differentiating into fibroblast-like cells that deposit extracellular matrix to seal the lesion and form
the persistent stromal scar core.
The aim of the proposal is to determine whether type A pericytes are a general source of
pathological connective tissue in the CNS, to understand the nature of type A pericytes, and to
uncover the signaling mechanisms mediating their recruitment. By comparing several different
injury and disease models the proposed research intends to uncover common mechanisms of
scarring and fibrosis and to identify new targets for human treatment after CNS injury.
Summary
Damage to the central nervous system (CNS) often leads to persistent functional deficits, causing
great individual suffering and enormous cost to society. The manifestation of these deficits is
believed to be associated with the scar tissue that forms locally at lesions, causing permanent tissue
alteration and blocking regeneration.
Research on CNS scar tissue has primarily focused on astrocytes and it is often referred to as the
glial scar. However, although it has received much less attention, there is also a connective tissue or
stromal, non-glial, component of the scar.
While studying spinal cord injury-induced scarring, I recently discovered a new subpopulation of
perivascular cells, named type A pericytes, as a major source of connective scar tissue. Type A
pericytes are embedded in the vascular wall but proliferate and leave the blood vessel upon injury,
differentiating into fibroblast-like cells that deposit extracellular matrix to seal the lesion and form
the persistent stromal scar core.
The aim of the proposal is to determine whether type A pericytes are a general source of
pathological connective tissue in the CNS, to understand the nature of type A pericytes, and to
uncover the signaling mechanisms mediating their recruitment. By comparing several different
injury and disease models the proposed research intends to uncover common mechanisms of
scarring and fibrosis and to identify new targets for human treatment after CNS injury.
Max ERC Funding
1 750 000 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym RAT MIRROR CELL
Project Deconstructing action planning and action observation in parietal circuits in rats
Researcher (PI) Jonathan Whitlock
Host Institution (HI) NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU
Call Details Starting Grant (StG), LS5, ERC-2013-StG
Summary The posterior parietal cortex (PPC) mediates cognitive motor functions including motor planning and action understanding. The latter process is thought to occur via ‘mirror’ neurons, which fire both when an animal performs an action and when it observes a cohort performing the same action. The extraordinary tuning properties of PPC cells require the convergence of sensory and motor inputs from several areas, but the function of these inputs is ill-defined since it is not yet feasible in humans or primates to reversibly inhibit targeted anatomical projections. I propose to overcome this by studying PPC in rodents, and will apply optogenetic tools and multi-tetrode recordings to characterize the function of selected cortical inputs to PPC. Similar to motor planning functions for hand or eye movements in primates, the rodent PPC encodes upcoming locomotor movements, and a growing literature suggests that rodents have a mirror system. I thus propose two related research programmes focusing on action planning and the mirror mechanism. The first project will determine if behavioral coding in PPC changes between a foraging task, in which behavior is spontaneous, and during navigational planning in a working memory-based T-maze. I will then determine if silencing fronto-parietal anatomical connections at different phases of the T-maze tasks disrupts motor planning and decision making functions in PPC. Next, I will record from PPC while rats observe cohorts performing the T-maze task to determine if the rat PPC contains mirror neurons. If I find mirror cells in rats, I will optically silence visual and frontal inputs to PPC to determine if they confer mirror selectivity to PPC. These experiments will reveal the anatomical circuitry underlying action planning and the mirror system in a way which cannot be achieved in primate models, and will open the door for studying mirror cells in rodent models of human mental disorders, including autism and Fragile-X syndrome.
Summary
The posterior parietal cortex (PPC) mediates cognitive motor functions including motor planning and action understanding. The latter process is thought to occur via ‘mirror’ neurons, which fire both when an animal performs an action and when it observes a cohort performing the same action. The extraordinary tuning properties of PPC cells require the convergence of sensory and motor inputs from several areas, but the function of these inputs is ill-defined since it is not yet feasible in humans or primates to reversibly inhibit targeted anatomical projections. I propose to overcome this by studying PPC in rodents, and will apply optogenetic tools and multi-tetrode recordings to characterize the function of selected cortical inputs to PPC. Similar to motor planning functions for hand or eye movements in primates, the rodent PPC encodes upcoming locomotor movements, and a growing literature suggests that rodents have a mirror system. I thus propose two related research programmes focusing on action planning and the mirror mechanism. The first project will determine if behavioral coding in PPC changes between a foraging task, in which behavior is spontaneous, and during navigational planning in a working memory-based T-maze. I will then determine if silencing fronto-parietal anatomical connections at different phases of the T-maze tasks disrupts motor planning and decision making functions in PPC. Next, I will record from PPC while rats observe cohorts performing the T-maze task to determine if the rat PPC contains mirror neurons. If I find mirror cells in rats, I will optically silence visual and frontal inputs to PPC to determine if they confer mirror selectivity to PPC. These experiments will reveal the anatomical circuitry underlying action planning and the mirror system in a way which cannot be achieved in primate models, and will open the door for studying mirror cells in rodent models of human mental disorders, including autism and Fragile-X syndrome.
Max ERC Funding
1 500 000 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym sCENT
Project Cryptophane-Enhanced Trace Gas Spectroscopy for On-Chip Methane Detection
Researcher (PI) Jana JAGERSKA
Host Institution (HI) UNIVERSITETET I TROMSOE - NORGES ARKTISKE UNIVERSITET
Call Details Starting Grant (StG), PE7, ERC-2017-STG
Summary Sensitivity of on-chip gas sensors is still at least 2-3 orders of magnitude lower than what is needed for applications in atmospheric monitoring and climate research. For optical sensors, this comes as a natural consequence of miniaturization: sensitivity scales with interaction length, which is directly related to instrument size. The aim of this project is to explore a new concept of combined chemical and spectroscopic detection for on-chip sensing of methane, the principal component of natural gas and a potent climate forcer.
The sought-after sensitivity will be achieved by pre-concentrating gas molecules directly on a chip surface using cryptophanes, and subsequently detecting them using slow-light waveguides and mid-infrared laser absorption spectroscopy. Cryptophanes are macromolecular structures that can bind and thus pre-concentrate different small molecules, including methane. Spectroscopic detection of methane in a cryptophane host is an absolute novelty, and, if successful, it will not only contribute to unprecedented sensitivity enhancement, but will also address fundamental questions about the dynamics of small molecules upon encapsulation. The actual gas sensing will be realized using evanescent field interaction in photonic crystal waveguides, which exhibit both large evanescent field confinement and long effective interaction pathlengths due to the slow-light effect. The waveguide design alone is expected to improve the per-length sensitivity up to 10 times, while another 10 to 100-fold sensitivity enhancement is expected from the pre-concentration.
The targeted detection limit of 10 ppb will revolutionize current methods of atmospheric monitoring, enabling large-scale networks of integrated sensors for better quantification of global methane emissions. Beyond that, this method can be extended to the detection of other gases, e.g. CO2 and different volatile organic compounds with equally relevant applications in the medical domain.
Summary
Sensitivity of on-chip gas sensors is still at least 2-3 orders of magnitude lower than what is needed for applications in atmospheric monitoring and climate research. For optical sensors, this comes as a natural consequence of miniaturization: sensitivity scales with interaction length, which is directly related to instrument size. The aim of this project is to explore a new concept of combined chemical and spectroscopic detection for on-chip sensing of methane, the principal component of natural gas and a potent climate forcer.
The sought-after sensitivity will be achieved by pre-concentrating gas molecules directly on a chip surface using cryptophanes, and subsequently detecting them using slow-light waveguides and mid-infrared laser absorption spectroscopy. Cryptophanes are macromolecular structures that can bind and thus pre-concentrate different small molecules, including methane. Spectroscopic detection of methane in a cryptophane host is an absolute novelty, and, if successful, it will not only contribute to unprecedented sensitivity enhancement, but will also address fundamental questions about the dynamics of small molecules upon encapsulation. The actual gas sensing will be realized using evanescent field interaction in photonic crystal waveguides, which exhibit both large evanescent field confinement and long effective interaction pathlengths due to the slow-light effect. The waveguide design alone is expected to improve the per-length sensitivity up to 10 times, while another 10 to 100-fold sensitivity enhancement is expected from the pre-concentration.
The targeted detection limit of 10 ppb will revolutionize current methods of atmospheric monitoring, enabling large-scale networks of integrated sensors for better quantification of global methane emissions. Beyond that, this method can be extended to the detection of other gases, e.g. CO2 and different volatile organic compounds with equally relevant applications in the medical domain.
Max ERC Funding
1 499 749 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym SENSTRIATUM
Project Sensory Integration in the Striatal Microcircuit
Researcher (PI) Gilad Daniel Silberberg
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS5, ERC-2011-StG_20101109
Summary Motor behaviour requires the meaningful integration of a multitude of sensory information. The basal ganglia are essential for such sensory-motor processing and underlie motor planning, performance, and learning. The striatum is the input layer of the basal ganglia, acting as a “hub” that receives synaptic inputs from different brain regions, interacting primarily with the GABAergic striatal microcircuit. Sensory excitatory inputs to striatum arise from the thalamus and neocortex, targeting striatal projection neurons and interneurons.
Previous work in basal ganglia focused mainly on their role in motor and reward related functions, but the functional role of striatum in sensory processing is largely unknown. In this study I will elucidate the principles of sensory processing performed at the striatal microcircuit. In particular, I aim to answer these fundamental questions:
- How do striatal neurons integrate sensory input? How is sensory input from different sensory modalities integrated in the striatum? How are ipsi- and contralateral inputs integrated?
- What are the respective roles of cortical and thalamic sensory inputs in striatal function?
- How is the intra-striatal microcircuitry organized to support sensory integration?
To address these questions I will use a combination of electrophysiological, optical, and anatomical methods, including:
- In vivo whole-cell recordings from striatal neurons during visual and tactile stimulation.
- Multi-neuron whole-cell recordings in corticostriatal and thalamostriatal slices.
- Optical manipulation of identified neuronal subpopulations in slice and in vivo.
The proposed study will provide a new understanding of sensory processing at the level of basal ganglia and may provide insights regarding basal ganglia dysfunction.
Summary
Motor behaviour requires the meaningful integration of a multitude of sensory information. The basal ganglia are essential for such sensory-motor processing and underlie motor planning, performance, and learning. The striatum is the input layer of the basal ganglia, acting as a “hub” that receives synaptic inputs from different brain regions, interacting primarily with the GABAergic striatal microcircuit. Sensory excitatory inputs to striatum arise from the thalamus and neocortex, targeting striatal projection neurons and interneurons.
Previous work in basal ganglia focused mainly on their role in motor and reward related functions, but the functional role of striatum in sensory processing is largely unknown. In this study I will elucidate the principles of sensory processing performed at the striatal microcircuit. In particular, I aim to answer these fundamental questions:
- How do striatal neurons integrate sensory input? How is sensory input from different sensory modalities integrated in the striatum? How are ipsi- and contralateral inputs integrated?
- What are the respective roles of cortical and thalamic sensory inputs in striatal function?
- How is the intra-striatal microcircuitry organized to support sensory integration?
To address these questions I will use a combination of electrophysiological, optical, and anatomical methods, including:
- In vivo whole-cell recordings from striatal neurons during visual and tactile stimulation.
- Multi-neuron whole-cell recordings in corticostriatal and thalamostriatal slices.
- Optical manipulation of identified neuronal subpopulations in slice and in vivo.
The proposed study will provide a new understanding of sensory processing at the level of basal ganglia and may provide insights regarding basal ganglia dysfunction.
Max ERC Funding
1 494 445 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym SNOWISO
Project Signals from the Surface Snow: Post-Depositional Processes Controlling the Ice Core IsotopicFingerprint
Researcher (PI) Hans Christian Steen-Larsen
Host Institution (HI) UNIVERSITETET I BERGEN
Call Details Starting Grant (StG), PE10, ERC-2017-STG
Summary For the past 50 years, our use of ice core records as climate archives has relied on the fundamental assumption that the isotopic composition of precipitation deposited on the ice sheet surface determines the ice core water isotopic composition. Since the isotopic composition in precipitation is assumed to be governed by the state of the climate this has made ice core isotope records one of the most important proxies for reconstructing the past climate.
New simultaneous measurements of snow and water vapor isotopes have shown that the surface snow exchanges with the atmospheric water vapor isotope signal, altering the deposited precipitation isotope signal. This severely questions the standard paradigm for interpreting the ice core proxy record and gives rise to the hypothesis that the isotope record from an ice core is determined by a combination of the atmospheric water vapor isotope signal and the precipitation isotope signal.
The SNOWISO project will verify this new hypothesis by combining laboratory and field experiments with in-situ observations of snow and water vapor isotopes in Greenland and Antarctica. This will enable me to quantify and parameterize the snow-air isotope exchange and post-depositional processes. I will implement these results into an isotope-enabled Regional Climate Model with a snowpack module and benchmarked against in-situ observations. Using the coupled snow-atmosphere isotope model I will establish the isotopic shift due to post-depositional processes under different climate conditions. This will facilitate the use of the full suite of water isotopes to infer past changes in the climate system, specifically changes in ocean sea surface temperature and relative humidity.
By establishing how the water isotope signal is recorded in the snow, the SNOWISO project will build the foundation for future integration of isotope-enabled General Circulation Models with ice core records; this opens a new frontier in climate reconstruction.
Summary
For the past 50 years, our use of ice core records as climate archives has relied on the fundamental assumption that the isotopic composition of precipitation deposited on the ice sheet surface determines the ice core water isotopic composition. Since the isotopic composition in precipitation is assumed to be governed by the state of the climate this has made ice core isotope records one of the most important proxies for reconstructing the past climate.
New simultaneous measurements of snow and water vapor isotopes have shown that the surface snow exchanges with the atmospheric water vapor isotope signal, altering the deposited precipitation isotope signal. This severely questions the standard paradigm for interpreting the ice core proxy record and gives rise to the hypothesis that the isotope record from an ice core is determined by a combination of the atmospheric water vapor isotope signal and the precipitation isotope signal.
The SNOWISO project will verify this new hypothesis by combining laboratory and field experiments with in-situ observations of snow and water vapor isotopes in Greenland and Antarctica. This will enable me to quantify and parameterize the snow-air isotope exchange and post-depositional processes. I will implement these results into an isotope-enabled Regional Climate Model with a snowpack module and benchmarked against in-situ observations. Using the coupled snow-atmosphere isotope model I will establish the isotopic shift due to post-depositional processes under different climate conditions. This will facilitate the use of the full suite of water isotopes to infer past changes in the climate system, specifically changes in ocean sea surface temperature and relative humidity.
By establishing how the water isotope signal is recorded in the snow, the SNOWISO project will build the foundation for future integration of isotope-enabled General Circulation Models with ice core records; this opens a new frontier in climate reconstruction.
Max ERC Funding
1 497 260 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym SONGBIRD
Project SOphisticated 3D cell culture scaffolds for Next Generation Barrier-on-chip In vitro moDels
Researcher (PI) Maria TENJE
Host Institution (HI) UPPSALA UNIVERSITET
Call Details Starting Grant (StG), PE7, ERC-2017-STG
Summary The blood-brain barrier is a sophisticated biological barrier comprising several different cell types, structured in a well-defined order with the task to strictly control the passage of molecules - such as drugs against neurodegenerative diseases - from the blood into the brain. To reduce the ethical and economic costs of drug development, which in EU today uses
~10 million experimental animals every year, we must develop in vitro models of the blood-brain barrier with high in vivo correlation, as these are completely missing today.
SONGBIRD aims to achieve this with the scientific approach to
- Develop advanced microfabrication methods to handle biologically derived materials
- Structure the materials into heterogeneous 3D multi-layer suspended cell culture scaffolds
- Incorporate blood-brain barrier cells with precise control on location and order
- Integrated the 3D scaffolds into a microfluidic network as a miniaturised screening platform
The vision is to develop and validate versatile microfabrication methods to mechanically structure and physically handle soft biological materials to unlock the use of next generation animal-free barrier-on-chip models that can be used to speed up drug development, serve as screening platforms for nanotoxicology and help medical researchers to gain mechanistic insight in drug delivery. During SONGBIRD, I will focus on the blood-brain barrier due to its urgent relevance for drug development for the ageing population but the final processing tool-box will be suitable for realising in vitro models of any biological barrier in the future.
SONGBIRD is proposed to run for 60 months and will include researchers with expertise in microsystem engineering (PI), hydrogel synthesis and drug delivery. The expected output is a validated 3D barrier-on-chip model as well as a microfabrication toolbox for biological materials enabling transformation from 2D to 3D cell cultures in several other life science research areas.
Summary
The blood-brain barrier is a sophisticated biological barrier comprising several different cell types, structured in a well-defined order with the task to strictly control the passage of molecules - such as drugs against neurodegenerative diseases - from the blood into the brain. To reduce the ethical and economic costs of drug development, which in EU today uses
~10 million experimental animals every year, we must develop in vitro models of the blood-brain barrier with high in vivo correlation, as these are completely missing today.
SONGBIRD aims to achieve this with the scientific approach to
- Develop advanced microfabrication methods to handle biologically derived materials
- Structure the materials into heterogeneous 3D multi-layer suspended cell culture scaffolds
- Incorporate blood-brain barrier cells with precise control on location and order
- Integrated the 3D scaffolds into a microfluidic network as a miniaturised screening platform
The vision is to develop and validate versatile microfabrication methods to mechanically structure and physically handle soft biological materials to unlock the use of next generation animal-free barrier-on-chip models that can be used to speed up drug development, serve as screening platforms for nanotoxicology and help medical researchers to gain mechanistic insight in drug delivery. During SONGBIRD, I will focus on the blood-brain barrier due to its urgent relevance for drug development for the ageing population but the final processing tool-box will be suitable for realising in vitro models of any biological barrier in the future.
SONGBIRD is proposed to run for 60 months and will include researchers with expertise in microsystem engineering (PI), hydrogel synthesis and drug delivery. The expected output is a validated 3D barrier-on-chip model as well as a microfabrication toolbox for biological materials enabling transformation from 2D to 3D cell cultures in several other life science research areas.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym SurfaceInhibition
Project The role of 5HT3a inhibitory interneurons in sensory processing
Researcher (PI) Koen Gerard Aloïs Vervaeke
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary How do cortical circuits process sensory stimuli that leads to perception? Sensory input is encoded by complex interactions between principal excitatory neurons and a diverse population of inhibitory cells. Distinct inhibitory neurons control different subcellular domains of target principal neurons, suggesting specific roles of different cells during sensory processing. However, the individual contribution of these inhibitory subtypes to sensory processing remains poorly understood. This is mainly due to the technical challenges of recording the activity of identified cell types in-vivo, in response to quantified sensory stimuli. Therefore, I propose a novel approach based on four pillars: 1) An optically accessible circuit in the superficial layers of the cortex, comprised of inhibitory cells expressing the serotonin receptor 5HT3a, and the distal dendrites of pyramidal neurons. 2) A novel combination of electrophysiology and 3D two-photon imaging to simultaneously record the activity of morphologically identified 5HT3a cells and their dendritic targets. 3) A head-fixed perceptual decision task, whereby mice use their whiskers to determine the location of an object, allowing an accurate description of the sensory stimulus. 4) The integration of experimental data and computer models to gain mechanistic insights into circuit functions. The 5HT3a cells and the distal dendrites of pyramidal neurons receive ‘top-down’ contextual information from other cortical areas that is essential for constructing meaningful perceptions of sensory stimuli. Thus I hypothesize that 5HT3a cells influence sensory perceptions by controlling the excitability of the pyramidal cell distal dendrites that integrate top-down and sensory input. Thus, I will not only reveal novel functions of inhibitory neurons, I will also shed light on how top-down and sensory input is integrated, and I will provide novel methods to test the functions of other cell types in normal mice and disease models.
Summary
How do cortical circuits process sensory stimuli that leads to perception? Sensory input is encoded by complex interactions between principal excitatory neurons and a diverse population of inhibitory cells. Distinct inhibitory neurons control different subcellular domains of target principal neurons, suggesting specific roles of different cells during sensory processing. However, the individual contribution of these inhibitory subtypes to sensory processing remains poorly understood. This is mainly due to the technical challenges of recording the activity of identified cell types in-vivo, in response to quantified sensory stimuli. Therefore, I propose a novel approach based on four pillars: 1) An optically accessible circuit in the superficial layers of the cortex, comprised of inhibitory cells expressing the serotonin receptor 5HT3a, and the distal dendrites of pyramidal neurons. 2) A novel combination of electrophysiology and 3D two-photon imaging to simultaneously record the activity of morphologically identified 5HT3a cells and their dendritic targets. 3) A head-fixed perceptual decision task, whereby mice use their whiskers to determine the location of an object, allowing an accurate description of the sensory stimulus. 4) The integration of experimental data and computer models to gain mechanistic insights into circuit functions. The 5HT3a cells and the distal dendrites of pyramidal neurons receive ‘top-down’ contextual information from other cortical areas that is essential for constructing meaningful perceptions of sensory stimuli. Thus I hypothesize that 5HT3a cells influence sensory perceptions by controlling the excitability of the pyramidal cell distal dendrites that integrate top-down and sensory input. Thus, I will not only reveal novel functions of inhibitory neurons, I will also shed light on how top-down and sensory input is integrated, and I will provide novel methods to test the functions of other cell types in normal mice and disease models.
Max ERC Funding
1 350 000 €
Duration
Start date: 2015-12-01, End date: 2020-05-31
Project acronym TREATPD
Project Cell and gene therapy based approaches for treatment of Parkinson's disease: from models to clinics
Researcher (PI) Deniz Kirik
Host Institution (HI) LUNDS UNIVERSITET
Call Details Starting Grant (StG), LS5, ERC-2009-StG
Summary Parkinson s disease is one of the common causes of disability in the aging population, representing a major health problem for the affected individuals and a socioeconomic burden to the society. In the present proposal, the applicant puts forward an ambitious but feasible program to tackle a number of significant issues that remain unsolved in the field. He combines his strong track record in animal models of Parkinson s disease and novel cell and gene therapy-based therapeutic strategies with powerful bio-imaging techniques in order to make bold steps towards translation of new and better treatments to patients suffering from this illness. He does so in a manner that combines, on one hand, the strength of clearly-defined hypotheses and well-established tools for results towards clinical translation, with high-risk high-reward projects that hold the potential to yield ground-breaking discoveries in implementation of novel imaging techniques, on the other.
Summary
Parkinson s disease is one of the common causes of disability in the aging population, representing a major health problem for the affected individuals and a socioeconomic burden to the society. In the present proposal, the applicant puts forward an ambitious but feasible program to tackle a number of significant issues that remain unsolved in the field. He combines his strong track record in animal models of Parkinson s disease and novel cell and gene therapy-based therapeutic strategies with powerful bio-imaging techniques in order to make bold steps towards translation of new and better treatments to patients suffering from this illness. He does so in a manner that combines, on one hand, the strength of clearly-defined hypotheses and well-established tools for results towards clinical translation, with high-risk high-reward projects that hold the potential to yield ground-breaking discoveries in implementation of novel imaging techniques, on the other.
Max ERC Funding
1 508 940 €
Duration
Start date: 2009-11-01, End date: 2014-10-31