Project acronym CIRCUITASSEMBLY
Project Development of functional organization of the visual circuits in mice
Researcher (PI) Keisuke Yonehara
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary The key organizing principles that characterize neuronal systems include asymmetric, parallel, and topographic connectivity of the neural circuits. The main aim of my research is to elucidate the key principles underlying functional development of neural circuits by focusing on those organizing principles. I choose mouse visual system as my model since it contains all of these principles and provides sophisticated genetic tools to label and manipulate individual circuit components. My research is based on the central hypothesis that the mechanisms of brain development cannot be fully understood without first identifying individual functional cell types in adults, and then understanding how the functions of these cell types become established, using cell-type-specific molecular and synaptic mechanisms in developing animals. Recently, I have identified several transgenic mouse lines in which specific cell types in a visual center, the superior colliculus, are labeled with Cre recombinase in both developing and adult animals. Here I will take advantage of these mouse lines to ask fundamental questions about the functional development of neural circuits. First, how are distinct sensory features processed by the parallel topographic neuronal pathways, and how do they contribute to behavior? Second, what are the molecular and synaptic mechanisms that underlie developmental circuit plasticity for forming parallel topographic neuronal maps in the brain? Third, what are the molecular mechanisms that set up spatially asymmetric circuit connectivity without the need for sensory experience? I predict that my insights into the developmental mechanism of asymmetric, parallel, and topographic connectivity and circuit plasticity will be instructive when studying other brain circuits which contain similar organizing principles.
Summary
The key organizing principles that characterize neuronal systems include asymmetric, parallel, and topographic connectivity of the neural circuits. The main aim of my research is to elucidate the key principles underlying functional development of neural circuits by focusing on those organizing principles. I choose mouse visual system as my model since it contains all of these principles and provides sophisticated genetic tools to label and manipulate individual circuit components. My research is based on the central hypothesis that the mechanisms of brain development cannot be fully understood without first identifying individual functional cell types in adults, and then understanding how the functions of these cell types become established, using cell-type-specific molecular and synaptic mechanisms in developing animals. Recently, I have identified several transgenic mouse lines in which specific cell types in a visual center, the superior colliculus, are labeled with Cre recombinase in both developing and adult animals. Here I will take advantage of these mouse lines to ask fundamental questions about the functional development of neural circuits. First, how are distinct sensory features processed by the parallel topographic neuronal pathways, and how do they contribute to behavior? Second, what are the molecular and synaptic mechanisms that underlie developmental circuit plasticity for forming parallel topographic neuronal maps in the brain? Third, what are the molecular mechanisms that set up spatially asymmetric circuit connectivity without the need for sensory experience? I predict that my insights into the developmental mechanism of asymmetric, parallel, and topographic connectivity and circuit plasticity will be instructive when studying other brain circuits which contain similar organizing principles.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym CSUMECH
Project Cholesterol and Sugar Uptake Mechanisms
Researcher (PI) Bjoern Pedersen
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS1, ERC-2014-STG
Summary Cardiovascular disease, diabetes and cancer have a dramatic impact on modern society, and in great part are related to uptake of cholesterol and sugar. We still know surprisingly little about the molecular details of the processes that goes on in this essential part of human basic metabolism. This application addresses cholesterol and sugar transport and aim to elucidate the molecular mechanism of cholesterol and sugar uptake in humans. It moves the frontiers of the field by shifting the focus to in vitro work allowing hitherto untried structural and biochemical experiments to be performed.
Cholesterol uptake from the intestine is mediated by the membrane protein NPC1L1. Despite extensive research, the molecular mechanism of NPC1L1-dependent cholesterol uptake still remains largely unknown.
Facilitated sugar transport in humans is made possible by sugar transporters called GLUTs and SWEETs, and every cell possesses these sugar transport systems. For all these uptake systems structural information is sorely lacking to address important mechanistic questions to help elucidate their molecular mechanism.
I will address this using a complementary set of methods founded in macromolecular crystallography and electron microscopy to determine the 3-dimensional structures of key players in these uptake systems. My unpublished preliminary results have established the feasibility of this approach. This will be followed up by biochemical characterization of the molecular mechanism in vitro and in silico.
This high risk/high reward membrane protein proposal could lead to a breakthrough in how we approach human biochemical pathways that are linked to trans-membrane transport. An improved understanding of cholesterol and sugar homeostasis has tremendous potential for improving general public health, and furthermore this proposal will help to uncover general principles of endocytotic uptake and facilitated diffusion systems at the molecular level.
Summary
Cardiovascular disease, diabetes and cancer have a dramatic impact on modern society, and in great part are related to uptake of cholesterol and sugar. We still know surprisingly little about the molecular details of the processes that goes on in this essential part of human basic metabolism. This application addresses cholesterol and sugar transport and aim to elucidate the molecular mechanism of cholesterol and sugar uptake in humans. It moves the frontiers of the field by shifting the focus to in vitro work allowing hitherto untried structural and biochemical experiments to be performed.
Cholesterol uptake from the intestine is mediated by the membrane protein NPC1L1. Despite extensive research, the molecular mechanism of NPC1L1-dependent cholesterol uptake still remains largely unknown.
Facilitated sugar transport in humans is made possible by sugar transporters called GLUTs and SWEETs, and every cell possesses these sugar transport systems. For all these uptake systems structural information is sorely lacking to address important mechanistic questions to help elucidate their molecular mechanism.
I will address this using a complementary set of methods founded in macromolecular crystallography and electron microscopy to determine the 3-dimensional structures of key players in these uptake systems. My unpublished preliminary results have established the feasibility of this approach. This will be followed up by biochemical characterization of the molecular mechanism in vitro and in silico.
This high risk/high reward membrane protein proposal could lead to a breakthrough in how we approach human biochemical pathways that are linked to trans-membrane transport. An improved understanding of cholesterol and sugar homeostasis has tremendous potential for improving general public health, and furthermore this proposal will help to uncover general principles of endocytotic uptake and facilitated diffusion systems at the molecular level.
Max ERC Funding
1 499 848 €
Duration
Start date: 2015-07-01, End date: 2020-12-31
Project acronym EUROHERIT
Project Legitimation of European cultural heritage and the dynamics of identity politics in the EU
Researcher (PI) Tuuli Kaarina Laehdesmaeki
Host Institution (HI) JYVASKYLAN YLIOPISTO
Country Finland
Call Details Starting Grant (StG), SH5, ERC-2014-STG
Summary The problematic of transnational cultural heritage has become topical in a new way in Europe with the utilization of the idea of heritage for political purposes in the EU policy. Since the turn of the century, the EU has launched or jointly administered several initiatives focusing on fostering the idea of a common European cultural heritage. The heritage initiatives are the EU’s ‘technologies of power’ aiming to legitimate and justify certain political ideas and ideologies, such as European-wide identity politics and the cultural integration in Europe. However, the politics, discourses, and practices of heritage—and of transnational heritage in particular—are often intertwined with contentions over its symbolical and factual ownership, meanings, and uses. The project investigates the EU as a new heritage agent and its heritage politics as an attempt to create a new trans-European heritage regime in Europe: How does the EU aim to create common European cultural heritage in a politically shaking and culturally diversified Europe, and what kind of explicit and implicit politics are included in its aims? The project will focus on the legitimation processes of European cultural heritage at different territorial levels and the power relations formed in the processes between diverse agencies. The academia still lacks a comparative empirical investigation on the politics and practices of trans-European cultural heritage and the theoretical discussion on the role of the EU in them. The project aims to respond to this lack with a broad comparative empirical research including cases from various parts of Europe, penetrating different territorial scales (local, regional, national, and the EU), and theorizing cultural heritage from a multisectional perspective (stressing its concurrent use in diverse societal domains and discourses). The project participates in a critical discussion on the current identity and integration politics and policies in the EU and Europe.
Summary
The problematic of transnational cultural heritage has become topical in a new way in Europe with the utilization of the idea of heritage for political purposes in the EU policy. Since the turn of the century, the EU has launched or jointly administered several initiatives focusing on fostering the idea of a common European cultural heritage. The heritage initiatives are the EU’s ‘technologies of power’ aiming to legitimate and justify certain political ideas and ideologies, such as European-wide identity politics and the cultural integration in Europe. However, the politics, discourses, and practices of heritage—and of transnational heritage in particular—are often intertwined with contentions over its symbolical and factual ownership, meanings, and uses. The project investigates the EU as a new heritage agent and its heritage politics as an attempt to create a new trans-European heritage regime in Europe: How does the EU aim to create common European cultural heritage in a politically shaking and culturally diversified Europe, and what kind of explicit and implicit politics are included in its aims? The project will focus on the legitimation processes of European cultural heritage at different territorial levels and the power relations formed in the processes between diverse agencies. The academia still lacks a comparative empirical investigation on the politics and practices of trans-European cultural heritage and the theoretical discussion on the role of the EU in them. The project aims to respond to this lack with a broad comparative empirical research including cases from various parts of Europe, penetrating different territorial scales (local, regional, national, and the EU), and theorizing cultural heritage from a multisectional perspective (stressing its concurrent use in diverse societal domains and discourses). The project participates in a critical discussion on the current identity and integration politics and policies in the EU and Europe.
Max ERC Funding
1 339 755 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym LimitMDR
Project Utilizing evolutionary interactions to limit multidrug resistance
Researcher (PI) Morten Otto Alexander Sommer
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS2, ERC-2014-STG
Summary Drug resistance is limiting our ability to treat most infectious diseases and forms of cancer. Indeed this relentless evolution is the major driver of treatment failure for diseases that are responsible for over half of the global disease related mortality. Yet, the underlying principles that guide this evolutionary response are poorly understood, in particular with regards to understanding the impact of multidrug treatment.
LimitMDR will characterize evolutionary trajectories leading to multidrug resistance in response to individual and combination drug treatment through the execution of large-scale adaptive evolution experiment with two bacterial pathogens followed by genome sequencing and phenotyping. This effort will enable testing of contrasting hypotheses regarding the evolution of multidrug resistance in response to combination treatment.
We will characterize the cause-and-effect of resistance and sensitivity mutations identified in our global data set and map comprehensive fitness landscapes of mutations accumulated during drug resistance evolution to understand the evolutionary dynamics underlying resistance evolution. To accomplish these bold goals we shall develop novel multiplexed methodologies enabling unprecedented scale of construction and phenotypic testing of identified mutations. While genetic epistasis is considered of key importance to resistance evolution most studies focus on mutations within an individual gene. Through the development of a novel experimental approach we shall elucidate complex epistatic interaction networks between mutations accumulated during resistance evolution.
Finally, we will conduct mechanistic studies to uncover the mechanisms of collateral sensitivity. These studies will shed light on this underappreciated phenomenon, which is of critical relevance to drug discovery and the evolution of drug resistance. In conclusion LimitMDR will develop groundbreaking novel methodologies and scientific insights that will c
Summary
Drug resistance is limiting our ability to treat most infectious diseases and forms of cancer. Indeed this relentless evolution is the major driver of treatment failure for diseases that are responsible for over half of the global disease related mortality. Yet, the underlying principles that guide this evolutionary response are poorly understood, in particular with regards to understanding the impact of multidrug treatment.
LimitMDR will characterize evolutionary trajectories leading to multidrug resistance in response to individual and combination drug treatment through the execution of large-scale adaptive evolution experiment with two bacterial pathogens followed by genome sequencing and phenotyping. This effort will enable testing of contrasting hypotheses regarding the evolution of multidrug resistance in response to combination treatment.
We will characterize the cause-and-effect of resistance and sensitivity mutations identified in our global data set and map comprehensive fitness landscapes of mutations accumulated during drug resistance evolution to understand the evolutionary dynamics underlying resistance evolution. To accomplish these bold goals we shall develop novel multiplexed methodologies enabling unprecedented scale of construction and phenotypic testing of identified mutations. While genetic epistasis is considered of key importance to resistance evolution most studies focus on mutations within an individual gene. Through the development of a novel experimental approach we shall elucidate complex epistatic interaction networks between mutations accumulated during resistance evolution.
Finally, we will conduct mechanistic studies to uncover the mechanisms of collateral sensitivity. These studies will shed light on this underappreciated phenomenon, which is of critical relevance to drug discovery and the evolution of drug resistance. In conclusion LimitMDR will develop groundbreaking novel methodologies and scientific insights that will c
Max ERC Funding
1 492 453 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym MECTRL
Project Measurement-based dynamic control of mesoscopic many-body systems
Researcher (PI) Jacob Friis Sherson
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), PE2, ERC-2014-STG
Summary Quantum control is an ambitious framework for steering dynamics from initial states to arbitrary desired final states. It has over the past decade been used extensively with immense success for control of low- dimensional systems in as varied fields as molecular dynamics and quantum computation. Only recently have efforts been initiated to extend this to higher-dimensional many-body systems. Most generic quantum control schemes to date, however, put quite heavy requirements on the controllability of either the system Hamiltonian or a set of measurement operators. This will in many realistic scenarios prohibit an efficient realization.
Within this proposal, I will develop a new quantum control scheme, which is minimalistic on system requirements and therefore ideally suited for the efficient and reliable optimization of many-body control problems. The fundamentally new ingredient is the total quantum evolution dictated by a combination of fixed many-body time evolution and the precise knowledge of the quantum back-action due to repeated quantum non-destruction (QND) measurements of a single projection operator.
The main focus of this proposal is theoretical and experimental quantum engineering of the dynamics in systems, which are sufficiently small to calculate the measurement back-action exactly and sufficiently large to have interesting many-body properties.
Recent experimental advances in single site manipulation of bosons in optical lattices have enabled the high fidelity preparation exactly such mesoscopic samples of atoms (5-50). This forms an ideal starting point for many-body quantum control, and we will i.a. demonstrate engineering of quantum phase transitions and preparation of highly non-classical Schödinger cat states.
Finally, using the results from an online graphical interface allowing users of the internet to solve quantum problems we will attempt to build next-generation optimization computer algorithms with a higher level of cognition built in.
Summary
Quantum control is an ambitious framework for steering dynamics from initial states to arbitrary desired final states. It has over the past decade been used extensively with immense success for control of low- dimensional systems in as varied fields as molecular dynamics and quantum computation. Only recently have efforts been initiated to extend this to higher-dimensional many-body systems. Most generic quantum control schemes to date, however, put quite heavy requirements on the controllability of either the system Hamiltonian or a set of measurement operators. This will in many realistic scenarios prohibit an efficient realization.
Within this proposal, I will develop a new quantum control scheme, which is minimalistic on system requirements and therefore ideally suited for the efficient and reliable optimization of many-body control problems. The fundamentally new ingredient is the total quantum evolution dictated by a combination of fixed many-body time evolution and the precise knowledge of the quantum back-action due to repeated quantum non-destruction (QND) measurements of a single projection operator.
The main focus of this proposal is theoretical and experimental quantum engineering of the dynamics in systems, which are sufficiently small to calculate the measurement back-action exactly and sufficiently large to have interesting many-body properties.
Recent experimental advances in single site manipulation of bosons in optical lattices have enabled the high fidelity preparation exactly such mesoscopic samples of atoms (5-50). This forms an ideal starting point for many-body quantum control, and we will i.a. demonstrate engineering of quantum phase transitions and preparation of highly non-classical Schödinger cat states.
Finally, using the results from an online graphical interface allowing users of the internet to solve quantum problems we will attempt to build next-generation optimization computer algorithms with a higher level of cognition built in.
Max ERC Funding
1 499 406 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym META-STRESS
Project Unravelling life-history responses and underlying mechanisms to environmental stress in wild populations
Researcher (PI) Marjo Anna Kaarina Saastamoinen
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Starting Grant (StG), LS8, ERC-2014-STG
Summary Organisms in the wild are constantly challenged by environmental variation in e.g. resource quality. The goal of this project is to move beyond laboratory experiments to understand the mechanisms that allow organisms in the wild to cope with environmental stress. Understanding the responses and mechanisms operating in wild populations is critical for assessing the eco-evolutionary consequences of environmental stress.
The large metapopulation of the Glanville fritillary butterfly gives me a unique opportunity to study processes operating from genes within individuals all the way to metapopulation-level dynamics. I will use individuals sampled from families from specific local populations with known ecological background (based on > 20 years of data) to experimentally test the influence of environmental stress on life-history variation. I will combine these experiments with simultaneous life-history assessments on the siblings remaining in the wild, thus effectively coupling laboratory and field-based studies. I will integrate the ecological studies with molecular approaches to unravel the significance of different mechanisms – candidate genes, epigenetic inheritance and intestinal microbial communities – potentially influencing individual responses to environmental challenges. I will focus on the influence of host plant quality as an environmental stressor, which is known to greatly influence life histories in many organisms, and which can be manipulated in the laboratory and assessed in the wild.
The proposed research has potential for groundbreaking results in evolutionary ecology, as the results will increase our understanding of 1) how individual responses to unfavorable environmental conditions and the underlying mechanisms vary within and among local populations in a spatially and temporally heterogeneous environment, and 2) how the consequent life-history variation influences the ecological and microevolutionary dynamics of wild populations.
Summary
Organisms in the wild are constantly challenged by environmental variation in e.g. resource quality. The goal of this project is to move beyond laboratory experiments to understand the mechanisms that allow organisms in the wild to cope with environmental stress. Understanding the responses and mechanisms operating in wild populations is critical for assessing the eco-evolutionary consequences of environmental stress.
The large metapopulation of the Glanville fritillary butterfly gives me a unique opportunity to study processes operating from genes within individuals all the way to metapopulation-level dynamics. I will use individuals sampled from families from specific local populations with known ecological background (based on > 20 years of data) to experimentally test the influence of environmental stress on life-history variation. I will combine these experiments with simultaneous life-history assessments on the siblings remaining in the wild, thus effectively coupling laboratory and field-based studies. I will integrate the ecological studies with molecular approaches to unravel the significance of different mechanisms – candidate genes, epigenetic inheritance and intestinal microbial communities – potentially influencing individual responses to environmental challenges. I will focus on the influence of host plant quality as an environmental stressor, which is known to greatly influence life histories in many organisms, and which can be manipulated in the laboratory and assessed in the wild.
The proposed research has potential for groundbreaking results in evolutionary ecology, as the results will increase our understanding of 1) how individual responses to unfavorable environmental conditions and the underlying mechanisms vary within and among local populations in a spatially and temporally heterogeneous environment, and 2) how the consequent life-history variation influences the ecological and microevolutionary dynamics of wild populations.
Max ERC Funding
1 494 883 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym OscillatoryVision
Project The retinae as windows to the brain: An oscillatory vision
Researcher (PI) Sarang Suresh Dalal
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), SH4, ERC-2014-STG
Summary Several sophisticated image processing circuits have been discovered in the animal retina, many of which manifest massive neural synchrony. A major insight is that this type of synchrony often translates to high-frequency activity on a macroscopic level, but electroretinography (ERG) has not been tapped to examine this potential in humans. Bolstered by our compelling results combining ERG with magnetoencephalography (MEG), this project will address several open questions with respect to human visual processing:
1) Could variable retinal timing be linked to intrinsic image properties and pass on phase variance downstream to visual cortex? Our data suggests the retina responds to moving gratings and natural imagery with non-phase-locked high gamma oscillations (>65 Hz) just like visual cortex, and that slower ERG potentials exhibit strong phase-locking within stimuli but large phase variance across stimuli.
2) Do such retinal gamma band responses, both evoked and induced, directly drive some cortical gamma responses? Pilot data suggests that it can, through retinocortical coherence, our novel ERG-MEG mapping technique.
3) Several kinds of motion have now been shown to elicit massive synchrony in mammalian retina circuits. Does this also result in macroscopic high-frequency activity? If so, our experiments will finally reveal and characterize motion detection by the human retina.
4) Do efferent pathways to the retina exist in humans? We discovered that the ERG exhibits eyes-closed alpha waves strikingly similar to the classic EEG phenomenon and, leveraging our retinocortical coherence technique, that this activity is likely driven by contralateral occipital cortex. Then, can retinal responses be influenced by ongoing cortical activity?
Characterizing retinocortical interaction represents a complete paradigm shift that will be imperative for our understanding of neural synchrony in the human nervous system and enable several groundbreaking new avenues for research.
Summary
Several sophisticated image processing circuits have been discovered in the animal retina, many of which manifest massive neural synchrony. A major insight is that this type of synchrony often translates to high-frequency activity on a macroscopic level, but electroretinography (ERG) has not been tapped to examine this potential in humans. Bolstered by our compelling results combining ERG with magnetoencephalography (MEG), this project will address several open questions with respect to human visual processing:
1) Could variable retinal timing be linked to intrinsic image properties and pass on phase variance downstream to visual cortex? Our data suggests the retina responds to moving gratings and natural imagery with non-phase-locked high gamma oscillations (>65 Hz) just like visual cortex, and that slower ERG potentials exhibit strong phase-locking within stimuli but large phase variance across stimuli.
2) Do such retinal gamma band responses, both evoked and induced, directly drive some cortical gamma responses? Pilot data suggests that it can, through retinocortical coherence, our novel ERG-MEG mapping technique.
3) Several kinds of motion have now been shown to elicit massive synchrony in mammalian retina circuits. Does this also result in macroscopic high-frequency activity? If so, our experiments will finally reveal and characterize motion detection by the human retina.
4) Do efferent pathways to the retina exist in humans? We discovered that the ERG exhibits eyes-closed alpha waves strikingly similar to the classic EEG phenomenon and, leveraging our retinocortical coherence technique, that this activity is likely driven by contralateral occipital cortex. Then, can retinal responses be influenced by ongoing cortical activity?
Characterizing retinocortical interaction represents a complete paradigm shift that will be imperative for our understanding of neural synchrony in the human nervous system and enable several groundbreaking new avenues for research.
Max ERC Funding
1 499 850 €
Duration
Start date: 2016-03-01, End date: 2022-03-31
Project acronym Q-CEOM
Project Quantum Cavity Electro- and Opto-Mechanics
Researcher (PI) Albert Schliesser
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), PE2, ERC-2014-STG
Summary Nanomechanical oscillators have recently been realised in the quantum regime, by coupling them to a single mode of the electromagnetic field. Platforms using both superconducting microwave circuits and optical cavities have been employed—separately—for this purpose. Based on the PI's extensive contributions to these developments, we propose to explore the intriguing conceptual and experimental prospects of hybrid multimode systems involving microwave, mechanical and optical modes in the quantum regime, thus unifying the fields of quantum cavity optomechanics and electromechanics.
To reach this ambitious goal, an optomechanical system involving two optical modes and one mechanical mode will serve as testbed for quantum conversion and tripartite entanglement protocols. Particular attention will be devoted to the evasion of mechanical thermal noise through noise-resilient schemes, relying, for example, on mechanically dark Bogoliubov modes. This will enable the conservation of quantum coherence in spite of the inevitable coupling of the mechanical device to a thermal environment. The protocols, once established, will be transferred to a hybrid multimode system, consisting of a superconducting microwave resonator, a nanomechanical oscillator, and an optical cavity mode. In this system, we will explore unprecedented opportunities to transduce, entangle and amplify microwave and optical modes through a mechanical device.
The specific implementation proposed here opens new avenues for the ultralow-noise processing of microwave signals, with potential applications in radio astronomy or magnetic resonance imaging. In the quantum sciences, it bears great promise to overcome the dichotomy between superconducting circuit platforms for information processing, and flying optical photons for its communication. More generally, the schemes studied here can serve as a blueprint for mechanical transducers—coupling to spin, charge, and fields alike—in hybrid quantum systems.
Summary
Nanomechanical oscillators have recently been realised in the quantum regime, by coupling them to a single mode of the electromagnetic field. Platforms using both superconducting microwave circuits and optical cavities have been employed—separately—for this purpose. Based on the PI's extensive contributions to these developments, we propose to explore the intriguing conceptual and experimental prospects of hybrid multimode systems involving microwave, mechanical and optical modes in the quantum regime, thus unifying the fields of quantum cavity optomechanics and electromechanics.
To reach this ambitious goal, an optomechanical system involving two optical modes and one mechanical mode will serve as testbed for quantum conversion and tripartite entanglement protocols. Particular attention will be devoted to the evasion of mechanical thermal noise through noise-resilient schemes, relying, for example, on mechanically dark Bogoliubov modes. This will enable the conservation of quantum coherence in spite of the inevitable coupling of the mechanical device to a thermal environment. The protocols, once established, will be transferred to a hybrid multimode system, consisting of a superconducting microwave resonator, a nanomechanical oscillator, and an optical cavity mode. In this system, we will explore unprecedented opportunities to transduce, entangle and amplify microwave and optical modes through a mechanical device.
The specific implementation proposed here opens new avenues for the ultralow-noise processing of microwave signals, with potential applications in radio astronomy or magnetic resonance imaging. In the quantum sciences, it bears great promise to overcome the dichotomy between superconducting circuit platforms for information processing, and flying optical photons for its communication. More generally, the schemes studied here can serve as a blueprint for mechanical transducers—coupling to spin, charge, and fields alike—in hybrid quantum systems.
Max ERC Funding
1 495 073 €
Duration
Start date: 2015-07-01, End date: 2021-06-30
Project acronym RevMito
Project Deciphering and reversing the consequences of mitochondrial DNA damage
Researcher (PI) Cory Dunn
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Starting Grant (StG), LS3, ERC-2014-STG
Summary Mitochondrial DNA (mtDNA) encodes several proteins playing key roles in bioenergetics. Pathological mutations of mtDNA can be inherited or may accumulate following treatment for viral infections or cancer. Furthermore, many organisms, including humans, accumulate significant mtDNA damage during their lifespan, and it is therefore possible that mtDNA mutations can promote the aging process.
There are no effective treatments for most diseases caused by mtDNA mutation. An understanding of the cellular consequences of mtDNA damage is clearly imperative. Toward this goal, we use the budding yeast Saccharomyces cerevisiae as a cellular model of mitochondrial dysfunction. Genetic manipulation and biochemical study of this organism is easily achieved, and many proteins and processes important for mitochondrial biogenesis were first uncovered and best characterized using this experimental system. Importantly, current evidence suggests that processes required for survival of cells lacking a mitochondrial genome are widely conserved between yeast and other organisms, making likely the application of our findings to human health.
We will study the repercussions of mtDNA damage by three different strategies. First, we will investigate the link between a conserved, nutrient-sensitive signalling pathway and the outcome of mtDNA loss, since much recent evidence points to modulation of such pathways as a potential approach to increase the fitness of cells with mtDNA damage. Second, we will explore the possibility that defects in cytosolic proteostasis are precipitated by mtDNA mutation. Third, we will apply the knowledge and concepts gained in S. cerevisiae to both candidate-based and unbiased searches for genes that determine the aftermath of severe mtDNA damage in human cells. Beyond the mechanistic knowledge of mitochondrial dysfunction that will emerge from this project, we expect to identify new avenues toward the treatment of mitochondrial disease.
Summary
Mitochondrial DNA (mtDNA) encodes several proteins playing key roles in bioenergetics. Pathological mutations of mtDNA can be inherited or may accumulate following treatment for viral infections or cancer. Furthermore, many organisms, including humans, accumulate significant mtDNA damage during their lifespan, and it is therefore possible that mtDNA mutations can promote the aging process.
There are no effective treatments for most diseases caused by mtDNA mutation. An understanding of the cellular consequences of mtDNA damage is clearly imperative. Toward this goal, we use the budding yeast Saccharomyces cerevisiae as a cellular model of mitochondrial dysfunction. Genetic manipulation and biochemical study of this organism is easily achieved, and many proteins and processes important for mitochondrial biogenesis were first uncovered and best characterized using this experimental system. Importantly, current evidence suggests that processes required for survival of cells lacking a mitochondrial genome are widely conserved between yeast and other organisms, making likely the application of our findings to human health.
We will study the repercussions of mtDNA damage by three different strategies. First, we will investigate the link between a conserved, nutrient-sensitive signalling pathway and the outcome of mtDNA loss, since much recent evidence points to modulation of such pathways as a potential approach to increase the fitness of cells with mtDNA damage. Second, we will explore the possibility that defects in cytosolic proteostasis are precipitated by mtDNA mutation. Third, we will apply the knowledge and concepts gained in S. cerevisiae to both candidate-based and unbiased searches for genes that determine the aftermath of severe mtDNA damage in human cells. Beyond the mechanistic knowledge of mitochondrial dysfunction that will emerge from this project, we expect to identify new avenues toward the treatment of mitochondrial disease.
Max ERC Funding
1 497 160 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym RiP
Project Rationality in Perception: Transformations of Mind and Cognition 1250-1550
Researcher (PI) Jose Filipe Pereira da Silva
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Starting Grant (StG), SH5, ERC-2014-STG
Summary The project RiP aims to provide a groundbreaking new interpretation of late medieval theories of mind and cognition by focusing on the influence higher cognitive (rational) powers exert on lower (sensory) ones in the neglected tradition of Augustinian philosophy of perception.
Due to increasing difficulties in explaining the unity and objectivity of perceptual experience, late medieval authors came to question the dominant Aristotelian theory, with its passive account of perception and emphatic separation between sensory and intellectual functions. This led to a resurfacing of the Augustinian tradition, which is characterized by an emphasis on activity and top-down processing, built around the notions of intentionality and self-awareness.
The project investigates the hypothesis that perception changes from being explained on the basis of a model of the soul that is metaphysically composite of really distinct clusters of functions to a model in which rationality permeates the functions previously attributed to lower cognitive capacities. It is the 'flow of reason', an expression found in a late sixteenth-century textbook.
The project has therefore two main objectives:
(1) to offer the first systematic study of late medieval theories of perception, focusing on the relation between the senses and intellect
(2) to retrace the shift in late medieval philosophy of perception that led to (a) a progressive questioning of direct realism in cognition and (b) the incremental reduction of all psychological functions to the mind.
The results of the project will allow a better understanding of the philosophical assumptions of late medieval theories of cognition, shedding new light on the historical background of early modern and contemporary conceptions of rationality.
Summary
The project RiP aims to provide a groundbreaking new interpretation of late medieval theories of mind and cognition by focusing on the influence higher cognitive (rational) powers exert on lower (sensory) ones in the neglected tradition of Augustinian philosophy of perception.
Due to increasing difficulties in explaining the unity and objectivity of perceptual experience, late medieval authors came to question the dominant Aristotelian theory, with its passive account of perception and emphatic separation between sensory and intellectual functions. This led to a resurfacing of the Augustinian tradition, which is characterized by an emphasis on activity and top-down processing, built around the notions of intentionality and self-awareness.
The project investigates the hypothesis that perception changes from being explained on the basis of a model of the soul that is metaphysically composite of really distinct clusters of functions to a model in which rationality permeates the functions previously attributed to lower cognitive capacities. It is the 'flow of reason', an expression found in a late sixteenth-century textbook.
The project has therefore two main objectives:
(1) to offer the first systematic study of late medieval theories of perception, focusing on the relation between the senses and intellect
(2) to retrace the shift in late medieval philosophy of perception that led to (a) a progressive questioning of direct realism in cognition and (b) the incremental reduction of all psychological functions to the mind.
The results of the project will allow a better understanding of the philosophical assumptions of late medieval theories of cognition, shedding new light on the historical background of early modern and contemporary conceptions of rationality.
Max ERC Funding
1 415 628 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
