Project acronym 2DQP
Project Two-dimensional quantum photonics
Researcher (PI) Brian David GERARDOT
Host Institution (HI) HERIOT-WATT UNIVERSITY
Call Details Consolidator Grant (CoG), PE3, ERC-2016-COG
Summary Quantum optics, the study of how discrete packets of light (photons) and matter interact, has led to the development of remarkable new technologies which exploit the bizarre properties of quantum mechanics. These quantum technologies are primed to revolutionize the fields of communication, information processing, and metrology in the coming years. Similar to contemporary technologies, the future quantum machinery will likely consist of a semiconductor platform to create and process the quantum information. However, to date the demanding requirements on a quantum photonic platform have yet to be satisfied with conventional bulk (three-dimensional) semiconductors.
To surmount these well-known obstacles, a new paradigm in quantum photonics is required. Initiated by the recent discovery of single photon emitters in atomically flat (two-dimensional) semiconducting materials, 2DQP aims to be at the nucleus of a new approach by realizing quantum optics with ultra-stable (coherent) quantum states integrated into devices with electronic and photonic functionality. We will characterize, identify, engineer, and coherently manipulate localized quantum states in this two-dimensional quantum photonic platform. A vital component of 2DQP’s vision is to go beyond the fundamental science and achieve the ideal solid-state single photon device yielding perfect extraction - 100% efficiency - of on-demand indistinguishable single photons. Finally, we will exploit this ideal device to implement the critical building block for a photonic quantum computer.
Summary
Quantum optics, the study of how discrete packets of light (photons) and matter interact, has led to the development of remarkable new technologies which exploit the bizarre properties of quantum mechanics. These quantum technologies are primed to revolutionize the fields of communication, information processing, and metrology in the coming years. Similar to contemporary technologies, the future quantum machinery will likely consist of a semiconductor platform to create and process the quantum information. However, to date the demanding requirements on a quantum photonic platform have yet to be satisfied with conventional bulk (three-dimensional) semiconductors.
To surmount these well-known obstacles, a new paradigm in quantum photonics is required. Initiated by the recent discovery of single photon emitters in atomically flat (two-dimensional) semiconducting materials, 2DQP aims to be at the nucleus of a new approach by realizing quantum optics with ultra-stable (coherent) quantum states integrated into devices with electronic and photonic functionality. We will characterize, identify, engineer, and coherently manipulate localized quantum states in this two-dimensional quantum photonic platform. A vital component of 2DQP’s vision is to go beyond the fundamental science and achieve the ideal solid-state single photon device yielding perfect extraction - 100% efficiency - of on-demand indistinguishable single photons. Finally, we will exploit this ideal device to implement the critical building block for a photonic quantum computer.
Max ERC Funding
1 999 135 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym ALZSYN
Project Imaging synaptic contributors to dementia
Researcher (PI) Tara Spires-Jones
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Consolidator Grant (CoG), LS5, ERC-2015-CoG
Summary Alzheimer's disease, the most common cause of dementia in older people, is a devastating condition that is becoming a public health crisis as our population ages. Despite great progress recently in Alzheimer’s disease research, we have no disease modifying drugs and a decade with a 99.6% failure rate of clinical trials attempting to treat the disease. This project aims to develop relevant therapeutic targets to restore brain function in Alzheimer’s disease by integrating human and model studies of synapses. It is widely accepted in the field that alterations in amyloid beta initiate the disease process. However the cascade leading from changes in amyloid to widespread tau pathology and neurodegeneration remain unclear. Synapse loss is the strongest pathological correlate of dementia in Alzheimer’s, and mounting evidence suggests that synapse degeneration plays a key role in causing cognitive decline. Here I propose to test the hypothesis that the amyloid cascade begins at the synapse leading to tau pathology, synapse dysfunction and loss, and ultimately neural circuit collapse causing cognitive impairment. The team will use cutting-edge multiphoton and array tomography imaging techniques to test mechanisms downstream of amyloid beta at synapses, and determine whether intervening in the cascade allows recovery of synapse structure and function. Importantly, I will combine studies in robust models of familial Alzheimer’s disease with studies in postmortem human brain to confirm relevance of our mechanistic studies to human disease. Finally, human stem cell derived neurons will be used to test mechanisms and potential therapeutics in neurons expressing the human proteome. Together, these experiments are ground-breaking since they have the potential to further our understanding of how synapses are lost in Alzheimer’s disease and to identify targets for effective therapeutic intervention, which is a critical unmet need in today’s health care system.
Summary
Alzheimer's disease, the most common cause of dementia in older people, is a devastating condition that is becoming a public health crisis as our population ages. Despite great progress recently in Alzheimer’s disease research, we have no disease modifying drugs and a decade with a 99.6% failure rate of clinical trials attempting to treat the disease. This project aims to develop relevant therapeutic targets to restore brain function in Alzheimer’s disease by integrating human and model studies of synapses. It is widely accepted in the field that alterations in amyloid beta initiate the disease process. However the cascade leading from changes in amyloid to widespread tau pathology and neurodegeneration remain unclear. Synapse loss is the strongest pathological correlate of dementia in Alzheimer’s, and mounting evidence suggests that synapse degeneration plays a key role in causing cognitive decline. Here I propose to test the hypothesis that the amyloid cascade begins at the synapse leading to tau pathology, synapse dysfunction and loss, and ultimately neural circuit collapse causing cognitive impairment. The team will use cutting-edge multiphoton and array tomography imaging techniques to test mechanisms downstream of amyloid beta at synapses, and determine whether intervening in the cascade allows recovery of synapse structure and function. Importantly, I will combine studies in robust models of familial Alzheimer’s disease with studies in postmortem human brain to confirm relevance of our mechanistic studies to human disease. Finally, human stem cell derived neurons will be used to test mechanisms and potential therapeutics in neurons expressing the human proteome. Together, these experiments are ground-breaking since they have the potential to further our understanding of how synapses are lost in Alzheimer’s disease and to identify targets for effective therapeutic intervention, which is a critical unmet need in today’s health care system.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym AMPHIBIANS
Project All Optical Manipulation of Photonic Metasurfaces for Biophotonic Applications in Microfluidic Environments
Researcher (PI) Andrea DI FALCO
Host Institution (HI) THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS
Call Details Consolidator Grant (CoG), PE7, ERC-2018-COG
Summary The current trend in biophotonics is to try and replicate the same ease and precision that our hands, eyes and ears offer at the macroscopic level, e.g. to hold, observe, squeeze and pull, rotate, cut and probe biological specimens in microfluidic environments. The bidding to get closer and closer to the object of interest has prompted the development of extremely advanced manipulation techniques at scales comparable to that of the wavelength of light. However, the fact that the optical beam can only access the microfluidic chip from the narrow aperture of a microscopic objective limits the versatility of the photonic function that can be realized.
With this project, the applicant proposes to introduce a new biophotonic platform based on the all optical manipulation of flexible photonic metasurfaces. These artificial two-dimensional materials have virtually arbitrary photonic responses and have an intrinsic exceptional mechanical stability. This cross-disciplinary project, bridging photonics, material sciences and biology, will enable the adoption of the most modern and advanced photonic designs in microfluidic environments, with transformative benefits for microscopy and biophotonic applications at the interface of molecular and cell biology.
Summary
The current trend in biophotonics is to try and replicate the same ease and precision that our hands, eyes and ears offer at the macroscopic level, e.g. to hold, observe, squeeze and pull, rotate, cut and probe biological specimens in microfluidic environments. The bidding to get closer and closer to the object of interest has prompted the development of extremely advanced manipulation techniques at scales comparable to that of the wavelength of light. However, the fact that the optical beam can only access the microfluidic chip from the narrow aperture of a microscopic objective limits the versatility of the photonic function that can be realized.
With this project, the applicant proposes to introduce a new biophotonic platform based on the all optical manipulation of flexible photonic metasurfaces. These artificial two-dimensional materials have virtually arbitrary photonic responses and have an intrinsic exceptional mechanical stability. This cross-disciplinary project, bridging photonics, material sciences and biology, will enable the adoption of the most modern and advanced photonic designs in microfluidic environments, with transformative benefits for microscopy and biophotonic applications at the interface of molecular and cell biology.
Max ERC Funding
1 999 524 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym C9ND
Project C9orf72-mediated neurodegeneration: mechanisms and therapeutics
Researcher (PI) Adrian Michael Isaacs
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Consolidator Grant (CoG), LS5, ERC-2014-CoG
Summary An expanded GGGGCC repeat in a non-coding region of the C9orf72 gene is the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The repeat RNA is transcribed and accumulates in neuronal RNA aggregates, implicating RNA toxicity as a key pathogenic mechanism. However, the pathways that lead to neurodegeneration are unknown. My lab has made pioneering contributions to the understanding of C9orf72 FTD/ALS, and reported the first structure of the repeat RNA, and the first description of both sense and antisense RNA aggregates in patient brain. We have now developed new disease models that allow, for the first time, the dissection of RNA toxicity both in vivo and in sophisticated neuronal culture models. We have also used our knowledge of the repeat structure to identify novel small molecules that show very strong binding to the repeats. We will utilise our innovative disease models in a multidisciplinary approach to fully dissect the cellular pathways underlying C9orf72 repeat RNA toxicity in vivo, on a genome-wide scale. Altered RNA metabolism has been implicated in a wide range of neurodegenerative diseases, indicating that our findings will provide profound new insight into fundamental mechanisms of neuronal maintenance and survival. This research programme will also deliver a step change in our understanding of C9orf72 FTD/ALS pathogenesis and provide essential insight for the identification of small molecules with genuine therapeutic potential. RNA-mediated mechanisms are now known to be a common theme in neurodegeneration, suggesting these findings will have broad significance.
Summary
An expanded GGGGCC repeat in a non-coding region of the C9orf72 gene is the most common known cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The repeat RNA is transcribed and accumulates in neuronal RNA aggregates, implicating RNA toxicity as a key pathogenic mechanism. However, the pathways that lead to neurodegeneration are unknown. My lab has made pioneering contributions to the understanding of C9orf72 FTD/ALS, and reported the first structure of the repeat RNA, and the first description of both sense and antisense RNA aggregates in patient brain. We have now developed new disease models that allow, for the first time, the dissection of RNA toxicity both in vivo and in sophisticated neuronal culture models. We have also used our knowledge of the repeat structure to identify novel small molecules that show very strong binding to the repeats. We will utilise our innovative disease models in a multidisciplinary approach to fully dissect the cellular pathways underlying C9orf72 repeat RNA toxicity in vivo, on a genome-wide scale. Altered RNA metabolism has been implicated in a wide range of neurodegenerative diseases, indicating that our findings will provide profound new insight into fundamental mechanisms of neuronal maintenance and survival. This research programme will also deliver a step change in our understanding of C9orf72 FTD/ALS pathogenesis and provide essential insight for the identification of small molecules with genuine therapeutic potential. RNA-mediated mechanisms are now known to be a common theme in neurodegeneration, suggesting these findings will have broad significance.
Max ERC Funding
1 985 699 €
Duration
Start date: 2015-10-01, End date: 2020-09-30
Project acronym Clock Mechanics
Project Mechanosensation and the circadian clock: a reciprocal analysis
Researcher (PI) Joerg Albert
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Consolidator Grant (CoG), LS5, ERC-2014-CoG
Summary All forms of life adjust themselves to the daily rhythms of their environments using endogenous oscillators collectively referred to as circadian clocks. Peripheral and central body clocks exist, which both require extrinsic information (e.g. light or temperature changes) to keep in sync with the geophysical cycle (entrainment). In addition, intrinsic cues (e.g. activity levels) have been linked to clock entrainment. Recently, we could show that activation of proprioceptors is sufficient to entrain the central clock of the fruit fly Drosophila melanogaster. Proprioceptors are mechanosensors that monitor the positions, and relative movements, of an animal’s own body parts. The existence of proprioceptive entrainment pathways has significant implications; it implies that an animal’s ‘clock time’ is computed by integrating, and weighting, various external and internal conditions, suggesting the existence of external and internal time.
Using Drosophila, I will investigate the relationship between mechanosensory and circadian systems in a dual, and bidirectional, approach. The project’s first aim is to dissect the neurobiological bases of proprioceptive clock entrainment (i) identifying the specific stimulus requirements for effective entrainment, (ii) determining its mechanosensory pathways and, in a combined computational and experimental strategy, (iii) quantifying the precise contributions of an animal’s activity to its sense of time. The project’s second aim, in turn, is to unravel the roles of the clock, and clock genes, for the function of mechanosensory systems. Previous studies have linked the clock to noise vulnerability in mammalian ears, and clock genes to regeneration in avian ears. Our own preliminary data reveal severe mechanosensory defects in flies mutant for core clock genes. I will use the Drosophila ear as a unifying model to analyse the specific roles of the clock, and clock genes, for the function of mechanotransducer systems.
Summary
All forms of life adjust themselves to the daily rhythms of their environments using endogenous oscillators collectively referred to as circadian clocks. Peripheral and central body clocks exist, which both require extrinsic information (e.g. light or temperature changes) to keep in sync with the geophysical cycle (entrainment). In addition, intrinsic cues (e.g. activity levels) have been linked to clock entrainment. Recently, we could show that activation of proprioceptors is sufficient to entrain the central clock of the fruit fly Drosophila melanogaster. Proprioceptors are mechanosensors that monitor the positions, and relative movements, of an animal’s own body parts. The existence of proprioceptive entrainment pathways has significant implications; it implies that an animal’s ‘clock time’ is computed by integrating, and weighting, various external and internal conditions, suggesting the existence of external and internal time.
Using Drosophila, I will investigate the relationship between mechanosensory and circadian systems in a dual, and bidirectional, approach. The project’s first aim is to dissect the neurobiological bases of proprioceptive clock entrainment (i) identifying the specific stimulus requirements for effective entrainment, (ii) determining its mechanosensory pathways and, in a combined computational and experimental strategy, (iii) quantifying the precise contributions of an animal’s activity to its sense of time. The project’s second aim, in turn, is to unravel the roles of the clock, and clock genes, for the function of mechanosensory systems. Previous studies have linked the clock to noise vulnerability in mammalian ears, and clock genes to regeneration in avian ears. Our own preliminary data reveal severe mechanosensory defects in flies mutant for core clock genes. I will use the Drosophila ear as a unifying model to analyse the specific roles of the clock, and clock genes, for the function of mechanotransducer systems.
Max ERC Funding
1 899 549 €
Duration
Start date: 2015-09-01, End date: 2021-08-31
Project acronym CNT-QUBIT
Project Carbon Nanotube Quantum Circuits
Researcher (PI) Mark Robertus Buitelaar
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Consolidator Grant (CoG), PE3, ERC-2014-CoG
Summary The aim of this proposal is to use spin qubits defined in carbon nanotube quantum dots to demonstrate measurement-based entanglement in an all-electrical and scalable solid-state architecture. The project makes use of spin-orbit interaction to drive spin rotations in the carbon nanotube host system and hyperfine interaction to store quantum information in the nuclear spin states. The proposal builds on techniques developed by the principal investigator for fast and non-invasive read-out of the electron spin qubits using radio-frequency reflectometry and spin-to-charge conversion.
Any quantum computer requires entanglement. One route to achieve entanglement between electron spin qubits in quantum dots is to use the direct interaction of neighbouring qubits due to their electron wavefunction overlap. This approach, however, becomes rapidly impractical for any large scale quantum processor, as distant qubits can only be entangled through the use of qubits in between. Here I propose an alternative strategy which makes use of an intriguing quantum mechanical effect by which two spatially separated spin qubits coupled to a single electrical resonator become entangled if a measurement cannot tell them apart.
The quantum information encoded in the entangled electron spin qubits will be transferred to carbon-13 nuclear spins which are used as a quantum memory with coherence times that exceed seconds. Entanglement with further qubits then proceeds again via projective measurements of the electron spin qubits without risk of losing the existing entanglement. When entanglement of the electron spin qubits is heralded – which might take several attempts – the quantum information is transferred again to the nuclear spin states. This allows for the coupling of large numbers of physically separated qubits, building up so-called graph or cluster states in an all-electrical and scalable solid-state architecture.
Summary
The aim of this proposal is to use spin qubits defined in carbon nanotube quantum dots to demonstrate measurement-based entanglement in an all-electrical and scalable solid-state architecture. The project makes use of spin-orbit interaction to drive spin rotations in the carbon nanotube host system and hyperfine interaction to store quantum information in the nuclear spin states. The proposal builds on techniques developed by the principal investigator for fast and non-invasive read-out of the electron spin qubits using radio-frequency reflectometry and spin-to-charge conversion.
Any quantum computer requires entanglement. One route to achieve entanglement between electron spin qubits in quantum dots is to use the direct interaction of neighbouring qubits due to their electron wavefunction overlap. This approach, however, becomes rapidly impractical for any large scale quantum processor, as distant qubits can only be entangled through the use of qubits in between. Here I propose an alternative strategy which makes use of an intriguing quantum mechanical effect by which two spatially separated spin qubits coupled to a single electrical resonator become entangled if a measurement cannot tell them apart.
The quantum information encoded in the entangled electron spin qubits will be transferred to carbon-13 nuclear spins which are used as a quantum memory with coherence times that exceed seconds. Entanglement with further qubits then proceeds again via projective measurements of the electron spin qubits without risk of losing the existing entanglement. When entanglement of the electron spin qubits is heralded – which might take several attempts – the quantum information is transferred again to the nuclear spin states. This allows for the coupling of large numbers of physically separated qubits, building up so-called graph or cluster states in an all-electrical and scalable solid-state architecture.
Max ERC Funding
1 998 574 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym DBSModel
Project Multiscale Modelling of the Neuromuscular System for Closed Loop Deep Brain Stimulation
Researcher (PI) Madeleine Mary Lowery
Host Institution (HI) UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Call Details Consolidator Grant (CoG), PE7, ERC-2014-CoG
Summary Deep brain stimulation (DBS) is an effective therapy for treating the symptoms of Parkinson’s disease (PD). Despite its success, the mechanisms of DBS are not understood and there is a need to improve DBS to improve long-term stimulation in a wider patient population, limit side-effects, and extend battery life. Currently DBS operates in ‘open-loop’, with stimulus parameters empirically set. Closed-loop DBS, which adjusts parameters based on the state of the system, has the potential to overcome current limitations to increase therapeutic efficacy while reducing side-effects, costs and energy. Several key questions need to be addressed before closed loop DBS can be implemented clinically.
This research will develop a new multiscale model of the neuromuscular system for closed-loop DBS. The model will simulate neural sensing and stimulation on a scale not previously considered, encompassing the electric field around the electrode, the effect on individual neurons and neural networks, and generation of muscle force. This will involve integration across multiple temporal and spatial scales, in a complex system with incomplete knowledge of system variables. Experiments will be conducted to validate the model, and identify new biomarkers of neural activity that can used with signals from the brain to enable continuous symptom monitoring. The model will be used to design a new control strategy for closed-loop DBS that can accommodate the nonlinear nature of the system, and short- and long-term changes in system behavior.
Though challenging, this research will provide new insights into the changes that take place in PD and the mechanisms by which DBS exerts its therapeutic influence. This knowledge will be used to design a new strategy for closed-loop DBS, ready for testing in patients, with the potential to significantly improve patient outcomes in PD and fundamentally change the way in which implanted devices utilise electrical stimulation to modulate neural activity.
Summary
Deep brain stimulation (DBS) is an effective therapy for treating the symptoms of Parkinson’s disease (PD). Despite its success, the mechanisms of DBS are not understood and there is a need to improve DBS to improve long-term stimulation in a wider patient population, limit side-effects, and extend battery life. Currently DBS operates in ‘open-loop’, with stimulus parameters empirically set. Closed-loop DBS, which adjusts parameters based on the state of the system, has the potential to overcome current limitations to increase therapeutic efficacy while reducing side-effects, costs and energy. Several key questions need to be addressed before closed loop DBS can be implemented clinically.
This research will develop a new multiscale model of the neuromuscular system for closed-loop DBS. The model will simulate neural sensing and stimulation on a scale not previously considered, encompassing the electric field around the electrode, the effect on individual neurons and neural networks, and generation of muscle force. This will involve integration across multiple temporal and spatial scales, in a complex system with incomplete knowledge of system variables. Experiments will be conducted to validate the model, and identify new biomarkers of neural activity that can used with signals from the brain to enable continuous symptom monitoring. The model will be used to design a new control strategy for closed-loop DBS that can accommodate the nonlinear nature of the system, and short- and long-term changes in system behavior.
Though challenging, this research will provide new insights into the changes that take place in PD and the mechanisms by which DBS exerts its therapeutic influence. This knowledge will be used to design a new strategy for closed-loop DBS, ready for testing in patients, with the potential to significantly improve patient outcomes in PD and fundamentally change the way in which implanted devices utilise electrical stimulation to modulate neural activity.
Max ERC Funding
1 999 474 €
Duration
Start date: 2015-08-01, End date: 2020-07-31
Project acronym DesignerPores
Project Understanding and Designing Novel NanoPores
Researcher (PI) Ulrich Felix Keyser
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Consolidator Grant (CoG), PE3, ERC-2014-CoG
Summary Translocation of ions and molecules is ubiquitous in biology and technology. Despite the tremendous amount of technical development, biological systems are still much more sophisticated in exerting exquisite control over active and passive translocation through nanopores in membranes than their existing synthetic mimics. This proposal aims to build novel designer nanopores that can match naturally evolved systems. For this we have to control all three stages of translocation: 1) diffusion and entry into, 2) diffusion in, and 3) exit from the nanopore. To gain fundamental insight into the translocation process we will employ microfluidic channels combined with holographic optical tweezers. Results from the microscale model system will be directly translated to nanoscale pores built with DNA origami nanotechnology. Our microfluidic experiments will automatically track diffusing spherical and non-spherical particles in artificial channels. Facilitated membrane transport will be mimicked by holographic optical tweezers providing full control over the translocation process. We will clarify how translocation depends on particle-particle, particle-channel, and particle-channel-entrance interactions.
The generic principles discovered on the microscale will guide the design of artificial nanopores made by DNA origami self-assembly. Our DNA origami based designer nanopores will lead to a novel class of transporters for molecules, ions, and water through solid-state and lipid membranes. The project will generate a quantitative understanding of membrane transport processes, test existing theoretical models with unprecedented experimental control, and introduce a novel approach to design active and passive nanopores built from DNA.
Summary
Translocation of ions and molecules is ubiquitous in biology and technology. Despite the tremendous amount of technical development, biological systems are still much more sophisticated in exerting exquisite control over active and passive translocation through nanopores in membranes than their existing synthetic mimics. This proposal aims to build novel designer nanopores that can match naturally evolved systems. For this we have to control all three stages of translocation: 1) diffusion and entry into, 2) diffusion in, and 3) exit from the nanopore. To gain fundamental insight into the translocation process we will employ microfluidic channels combined with holographic optical tweezers. Results from the microscale model system will be directly translated to nanoscale pores built with DNA origami nanotechnology. Our microfluidic experiments will automatically track diffusing spherical and non-spherical particles in artificial channels. Facilitated membrane transport will be mimicked by holographic optical tweezers providing full control over the translocation process. We will clarify how translocation depends on particle-particle, particle-channel, and particle-channel-entrance interactions.
The generic principles discovered on the microscale will guide the design of artificial nanopores made by DNA origami self-assembly. Our DNA origami based designer nanopores will lead to a novel class of transporters for molecules, ions, and water through solid-state and lipid membranes. The project will generate a quantitative understanding of membrane transport processes, test existing theoretical models with unprecedented experimental control, and introduce a novel approach to design active and passive nanopores built from DNA.
Max ERC Funding
1 936 431 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym DiSCo MRI SFN
Project Developing Integrated Susceptibility and Conductivity MRI for Next Generation Structural and Functional Neuroimaging
Researcher (PI) Karin SHMUELI
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Consolidator Grant (CoG), LS5, ERC-2017-COG
Summary MRI is indispensable in the diagnosis of neurodegenerative diseases. These are poorly understood while their prevalence and socio-economic burden continue to rise. Structural and functional MRI can provide biomarkers for early diagnosis and potential therapeutic intervention. My research vision is to develop novel MRI methods for structural and functional mapping of tissue magnetic susceptibility and electrical conductivity as these show great promise for neuroimaging in diseases such as Alzheimer’s (AD).
Susceptibility mapping (SM), which I pioneered, is uniquely sensitive to tissue composition including iron content affected in AD while conductivity mapping (CM) probably reflects cellular disruption in AD. Resting-state functional MRI (rsfMRI) reveals how AD affects brain networks without any tasks or stimulation equipment. However, each technique currently needs a separate time-consuming MRI scan. I will develop an integrated scan for simultaneous structural SM and CM, and rsfMRI functional connectivity characterisation. This efficient scan, ideal for AD patients, will reveal totally new resting-state networks based on electromagnetic properties: resting-state functional SM and resting-state functional CM for the first time. As changes in blood susceptibility underlie fMRI, rsfSM should measure functional connectivity more directly. This also makes it sensitive to physiological noise so I will develop noise removal methods building on fMRI techniques I established. Initial fSM studies have been at 7 Tesla but I will target the more widespread 3T field to maximise applicability. As a leader in both SM and rsfMRI physiological noise removal I have the ideal background to integrate SM and CM with fMRI and extend them for ground-breaking functional electromagnetic connectivity. This research will yield a rich set of novel, multimodal MRI contrasts to allow development of new combined structural and functional biomarkers for early diagnosis of AD and other diseases.
Summary
MRI is indispensable in the diagnosis of neurodegenerative diseases. These are poorly understood while their prevalence and socio-economic burden continue to rise. Structural and functional MRI can provide biomarkers for early diagnosis and potential therapeutic intervention. My research vision is to develop novel MRI methods for structural and functional mapping of tissue magnetic susceptibility and electrical conductivity as these show great promise for neuroimaging in diseases such as Alzheimer’s (AD).
Susceptibility mapping (SM), which I pioneered, is uniquely sensitive to tissue composition including iron content affected in AD while conductivity mapping (CM) probably reflects cellular disruption in AD. Resting-state functional MRI (rsfMRI) reveals how AD affects brain networks without any tasks or stimulation equipment. However, each technique currently needs a separate time-consuming MRI scan. I will develop an integrated scan for simultaneous structural SM and CM, and rsfMRI functional connectivity characterisation. This efficient scan, ideal for AD patients, will reveal totally new resting-state networks based on electromagnetic properties: resting-state functional SM and resting-state functional CM for the first time. As changes in blood susceptibility underlie fMRI, rsfSM should measure functional connectivity more directly. This also makes it sensitive to physiological noise so I will develop noise removal methods building on fMRI techniques I established. Initial fSM studies have been at 7 Tesla but I will target the more widespread 3T field to maximise applicability. As a leader in both SM and rsfMRI physiological noise removal I have the ideal background to integrate SM and CM with fMRI and extend them for ground-breaking functional electromagnetic connectivity. This research will yield a rich set of novel, multimodal MRI contrasts to allow development of new combined structural and functional biomarkers for early diagnosis of AD and other diseases.
Max ERC Funding
1 721 726 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym EvoStruc
Project The physics of antibiotic resistance evolution in spatially-structured multicellular assemblies
Researcher (PI) Rosalind Allen
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Consolidator Grant (CoG), PE3, ERC-2015-CoG
Summary The rise in bacterial infections that are resistant to antibiotic treatment poses a major global health challenge. Addressing this challenge is not just a clinical issue: understanding bacterial resistance evolution calls for an interdisciplinary approach, in which the development of new physics, in coordination with biology, chemistry and engineering, has a central role to play. In particular, statistical physics, to predict the stochastic emergence of drug-resistant mutants, must be integrated with soft matter and chemical physics, to understand the spatial organization of the bacterial populations within which this happens.
Bacterial infections are very often spatially heterogeneous. This is known to influence the outcome of antibiotic treatment – for example bacterial biofilms, which form on the surfaces of medical implants, are notoriously hard to remove. However, much less attention has been paid to the role of spatial structure in the evolution of drug resistance, i.e. the emergence and spread of genetically drug-resistant bacterial strains.
I will lead a research programme which will for the first time uncover the two-way link between the emergence of spatial structure in bacterial multicellular assemblies and the evolution of drug resistance. The programme builds on my current theoretical, simulation and experimental work. I will first determine the basic principles of evolution in drug gradients using theoretical models, combined with experiments in a controlled, 1D geometry. I will then explore how these principles translate to the more realistic scenario of bacterial biofilms, where spatial structure and drug gradients are emergent properties, using advanced computer simulation methods and both confocal microscopy and evolution experiments. In the final part of the programme, I will use these insights to reveal optimization principles for the design of evolution-resistant surface coatings for applications in medical devices.
Summary
The rise in bacterial infections that are resistant to antibiotic treatment poses a major global health challenge. Addressing this challenge is not just a clinical issue: understanding bacterial resistance evolution calls for an interdisciplinary approach, in which the development of new physics, in coordination with biology, chemistry and engineering, has a central role to play. In particular, statistical physics, to predict the stochastic emergence of drug-resistant mutants, must be integrated with soft matter and chemical physics, to understand the spatial organization of the bacterial populations within which this happens.
Bacterial infections are very often spatially heterogeneous. This is known to influence the outcome of antibiotic treatment – for example bacterial biofilms, which form on the surfaces of medical implants, are notoriously hard to remove. However, much less attention has been paid to the role of spatial structure in the evolution of drug resistance, i.e. the emergence and spread of genetically drug-resistant bacterial strains.
I will lead a research programme which will for the first time uncover the two-way link between the emergence of spatial structure in bacterial multicellular assemblies and the evolution of drug resistance. The programme builds on my current theoretical, simulation and experimental work. I will first determine the basic principles of evolution in drug gradients using theoretical models, combined with experiments in a controlled, 1D geometry. I will then explore how these principles translate to the more realistic scenario of bacterial biofilms, where spatial structure and drug gradients are emergent properties, using advanced computer simulation methods and both confocal microscopy and evolution experiments. In the final part of the programme, I will use these insights to reveal optimization principles for the design of evolution-resistant surface coatings for applications in medical devices.
Max ERC Funding
1 826 984 €
Duration
Start date: 2016-06-01, End date: 2022-05-31
Project acronym ExtremeQuantum
Project Quantum materials under extreme conditions
Researcher (PI) Paul Andrew Goddard
Host Institution (HI) THE UNIVERSITY OF WARWICK
Call Details Consolidator Grant (CoG), PE3, ERC-2015-CoG
Summary New states of matter offer an unparalleled testing ground for studying fundamental physics, particularly interacting quantum systems. The EXTREMEQUANTUM project will significantly advance our knowledge of these states by using extreme conditions of magnetic field and pressure to enable a continuous, clean and reversible tuning of quantum interactions, thereby shedding light on the building blocks of exotic magnetism and unconventional superconductivity. By developing the materials and methodology to achieve this, we will push our understanding of quantum systems beyond current limitations and open a route for exploiting the untapped potential of these materials to underpin future technology in fields as diverse as electrical power networks, quantum computation and healthcare.
EXTREMEQUANTUM takes as its starting point recent theoretical and experimental discoveries in the area of quantum materials and will capitalize on a novel measurement technique developed in my research group over the past few years. By utilizing both atomic and molecular substitution, the project will focus on a series of materials that are on the verge of a phase instability. Ultra-high fields and applied pressure will push these systems through the critical region where the state of matter changes and inherently quantum effects dominate. Electronic, magnetic and structural properties will be measured as the tipping point is breached and the resulting data compared with predictions of theoretical models. The results will provide answers to questions of deep concern to modern physics, such how quantum fluctuations, topology and disorder can be used to create states of matter with novel and functional properties.
Summary
New states of matter offer an unparalleled testing ground for studying fundamental physics, particularly interacting quantum systems. The EXTREMEQUANTUM project will significantly advance our knowledge of these states by using extreme conditions of magnetic field and pressure to enable a continuous, clean and reversible tuning of quantum interactions, thereby shedding light on the building blocks of exotic magnetism and unconventional superconductivity. By developing the materials and methodology to achieve this, we will push our understanding of quantum systems beyond current limitations and open a route for exploiting the untapped potential of these materials to underpin future technology in fields as diverse as electrical power networks, quantum computation and healthcare.
EXTREMEQUANTUM takes as its starting point recent theoretical and experimental discoveries in the area of quantum materials and will capitalize on a novel measurement technique developed in my research group over the past few years. By utilizing both atomic and molecular substitution, the project will focus on a series of materials that are on the verge of a phase instability. Ultra-high fields and applied pressure will push these systems through the critical region where the state of matter changes and inherently quantum effects dominate. Electronic, magnetic and structural properties will be measured as the tipping point is breached and the resulting data compared with predictions of theoretical models. The results will provide answers to questions of deep concern to modern physics, such how quantum fluctuations, topology and disorder can be used to create states of matter with novel and functional properties.
Max ERC Funding
1 840 513 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym FermiSurfaceFlavours
Project FLAVOURS OF FERMI SURFACE IN THE ABSENCE OF A CONVENTIONAL FERMI LIQUID
Researcher (PI) Suchitra SEBASTIAN
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Consolidator Grant (CoG), PE3, ERC-2017-COG
Summary Quantum oscillations have revealed signature Fermi surfaces in a diverse range of materials families, with breakthrough advances made by a synthesis of theoretical modelling, experimental vision, materials preparation, and advances in measurement technique. Traditionally, the very observation of a Fermi surface has been taken to imply an underlying Fermi liquid. In this proposal, we seek to transcend this traditional paradigm in the field of correlated electron systems and define a new framework for the observation of quantum oscillations associated with a novel Fermi surface in the absence of a conventional Fermi liquid. Guided by a selection of theoretical proposals, we identify for study materials families starting from the more readily modellable correlated Mott insulators and Kondo insulators without the complication of mobile electrons. We progress to regions where mobile electrons are introduced – where we select for study the doped Mott insulating cuprate superconductors. Eventually we access the intervening region of unconventional quantum critical physics where a Fermi surface in the absence of a conventional Fermi liquid transitions to a Fermi surface underpinned by a conventional Fermi liquid, by lattice-density tuning of selected materials. We propose to investigate the Fermi surface of these regimes of correlated materials phase space that defy conventional Fermi liquid behaviour by the use of advanced quantum oscillation techniques in selected high purity correlated materials, under either ambient pressure conditions or under lattice-density tuning, and using high magnetic fields. We expect the project outcome to have a substantive impact on our understanding of correlated electron systems, especially in hitherto opaque regions of phase space where Fermi liquid behaviour breaks down. We thus anticipate a new era where quantum oscillations serve as a diagnostic for novel phases of correlated matter that lack a conventional Fermi liquid description.
Summary
Quantum oscillations have revealed signature Fermi surfaces in a diverse range of materials families, with breakthrough advances made by a synthesis of theoretical modelling, experimental vision, materials preparation, and advances in measurement technique. Traditionally, the very observation of a Fermi surface has been taken to imply an underlying Fermi liquid. In this proposal, we seek to transcend this traditional paradigm in the field of correlated electron systems and define a new framework for the observation of quantum oscillations associated with a novel Fermi surface in the absence of a conventional Fermi liquid. Guided by a selection of theoretical proposals, we identify for study materials families starting from the more readily modellable correlated Mott insulators and Kondo insulators without the complication of mobile electrons. We progress to regions where mobile electrons are introduced – where we select for study the doped Mott insulating cuprate superconductors. Eventually we access the intervening region of unconventional quantum critical physics where a Fermi surface in the absence of a conventional Fermi liquid transitions to a Fermi surface underpinned by a conventional Fermi liquid, by lattice-density tuning of selected materials. We propose to investigate the Fermi surface of these regimes of correlated materials phase space that defy conventional Fermi liquid behaviour by the use of advanced quantum oscillation techniques in selected high purity correlated materials, under either ambient pressure conditions or under lattice-density tuning, and using high magnetic fields. We expect the project outcome to have a substantive impact on our understanding of correlated electron systems, especially in hitherto opaque regions of phase space where Fermi liquid behaviour breaks down. We thus anticipate a new era where quantum oscillations serve as a diagnostic for novel phases of correlated matter that lack a conventional Fermi liquid description.
Max ERC Funding
2 127 851 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym FLAMENCO
Project A Fully-Implantable MEMS-Based Autonomous Cochlear Implant
Researcher (PI) Kulah Haluk
Host Institution (HI) MIDDLE EAST TECHNICAL UNIVERSITY
Call Details Consolidator Grant (CoG), PE7, ERC-2015-CoG
Summary Sensorineural impairment, representing the majority of the profound deafness, can be restored using cochlear implants (CIs), which electrically stimulates the auditory nerve to repair hearing in people with severe-to-profound hearing loss. A conventional CI consists of an external microphone, a sound processor, a battery, an RF transceiver pair, and a cochlear electrode. The major drawback of conventional CIs is that, they replace the entire natural hearing mechanism with electronic hearing, even though most parts of the middle ear are operational. Also, the power hungry units such as microphone and RF transceiver cause limitations in continuous access to sound due to battery problems. Besides, damage risk of external components especially if exposed to water and aesthetic concerns are other critical problems. Limited volume of the middle ear is the main obstacle for developing fully implantable CIs.
FLAMENCO proposes a fully implantable, autonomous, and low-power CI, exploiting the functional parts of the middle ear and mimicking the hair cells via a set of piezoelectric cantilevers to cover the daily acoustic band. FLAMENCO has a groundbreaking nature as it revolutionizes the operation principle of CIs. The implant has five main units: i) piezoelectric transducers for sound detection and energy harvesting, ii) electronics for signal processing and battery charging, iii) an RF coil for tuning the electronics to allow customization, iv) rechargeable battery, and v) cochlear electrode for neural stimulation. The utilization of internal energy harvesting together with the elimination of continuous RF transmission, microphone, and front-end filters makes this system a perfect candidate for next generation autonomous CIs. In this project, a multi-frequency self-powered implant for in vivo operation will be implemented, and the feasibility will be proven through animal tests.
Summary
Sensorineural impairment, representing the majority of the profound deafness, can be restored using cochlear implants (CIs), which electrically stimulates the auditory nerve to repair hearing in people with severe-to-profound hearing loss. A conventional CI consists of an external microphone, a sound processor, a battery, an RF transceiver pair, and a cochlear electrode. The major drawback of conventional CIs is that, they replace the entire natural hearing mechanism with electronic hearing, even though most parts of the middle ear are operational. Also, the power hungry units such as microphone and RF transceiver cause limitations in continuous access to sound due to battery problems. Besides, damage risk of external components especially if exposed to water and aesthetic concerns are other critical problems. Limited volume of the middle ear is the main obstacle for developing fully implantable CIs.
FLAMENCO proposes a fully implantable, autonomous, and low-power CI, exploiting the functional parts of the middle ear and mimicking the hair cells via a set of piezoelectric cantilevers to cover the daily acoustic band. FLAMENCO has a groundbreaking nature as it revolutionizes the operation principle of CIs. The implant has five main units: i) piezoelectric transducers for sound detection and energy harvesting, ii) electronics for signal processing and battery charging, iii) an RF coil for tuning the electronics to allow customization, iv) rechargeable battery, and v) cochlear electrode for neural stimulation. The utilization of internal energy harvesting together with the elimination of continuous RF transmission, microphone, and front-end filters makes this system a perfect candidate for next generation autonomous CIs. In this project, a multi-frequency self-powered implant for in vivo operation will be implemented, and the feasibility will be proven through animal tests.
Max ERC Funding
1 993 750 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym FOGHORN
Project FOG-aided wireless networks for communication, cacHing and cOmputing: theoRetical and algorithmic fouNdations
Researcher (PI) Osvaldo SIMEONE
Host Institution (HI) KING'S COLLEGE LONDON
Call Details Consolidator Grant (CoG), PE7, ERC-2016-COG
Summary "The FOGHORN project aims at developing the theoretical and algorithmic foundations of fog-aided wireless networks. This is an emerging class of wireless systems that leverages the synergy and complementarity of cloudification and edge processing, two key technologies in the evolution towards 5G systems and beyond. Fog-aided wireless networks can reap the bene
fits of centralization via cloud processing, in terms of capital and operating cost reductions, greening, and
enhanced spectral e fficiency, while, at the same time, being able to cater to low-latency applications, such as the ""tactile"" internet, by means of localized intelligence at the network edge. The operation of fog-aided wireless networks poses novel fundamental research problems pertaining to the optimal management of the communication, caching and computing resources at the
cloud and at the edge, as well as to the transmission on the fronthaul network connecting cloud and edge. The solution of these problems challenges the theoretical principles and engineering insights which have underpinned the design of existing networks. The initial research activity on the topic, of which the EU is at the forefront, focuses, by and large, on ad hoc solutions and technologies. In contrast, the goal of this project is to develop fundamental theoretical insights
and algorithmic principles with the main aim of guiding engineering choices, unlocking new academic opportunities and disclosing new technologies. The theoretical framework is grounded in network information theory, which enables the distillation of design principles, along with signal processing, (non-convex) optimization, queuing and distributed computing to develop and analyse algorithmic solutions."
Summary
"The FOGHORN project aims at developing the theoretical and algorithmic foundations of fog-aided wireless networks. This is an emerging class of wireless systems that leverages the synergy and complementarity of cloudification and edge processing, two key technologies in the evolution towards 5G systems and beyond. Fog-aided wireless networks can reap the bene
fits of centralization via cloud processing, in terms of capital and operating cost reductions, greening, and
enhanced spectral e fficiency, while, at the same time, being able to cater to low-latency applications, such as the ""tactile"" internet, by means of localized intelligence at the network edge. The operation of fog-aided wireless networks poses novel fundamental research problems pertaining to the optimal management of the communication, caching and computing resources at the
cloud and at the edge, as well as to the transmission on the fronthaul network connecting cloud and edge. The solution of these problems challenges the theoretical principles and engineering insights which have underpinned the design of existing networks. The initial research activity on the topic, of which the EU is at the forefront, focuses, by and large, on ad hoc solutions and technologies. In contrast, the goal of this project is to develop fundamental theoretical insights
and algorithmic principles with the main aim of guiding engineering choices, unlocking new academic opportunities and disclosing new technologies. The theoretical framework is grounded in network information theory, which enables the distillation of design principles, along with signal processing, (non-convex) optimization, queuing and distributed computing to develop and analyse algorithmic solutions."
Max ERC Funding
2 318 719 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym FUNCOPLAN
Project Functions of plasticity in adult-born neurons
Researcher (PI) Matthew Stuart GRUBB
Host Institution (HI) KING'S COLLEGE LONDON
Call Details Consolidator Grant (CoG), LS5, ERC-2016-COG
Summary The major objective of FUNCOPLAN is to examine groundbreaking questions on the functional role of newly-generated neurons in the adult brain. Using a combination of innovative approaches, our aim is to discover how plasticity in adult-born cells shapes information processing in neuronal circuits.
Adult neurogenesis produces new neurons in particular areas of the mammalian brain throughout life. Because they undergo a transient period of heightened plasticity, these freshly-generated cells are believed to bring unique properties to the circuits they join – a continual influx of new, immature cells is believed to provide a level of plasticity not achievable by the mature, resident network alone. But what exactly is the function of the additional plasticity provided by adult-born neurons? How does it influence information processing in neuronal networks?
These questions are vital for our fundamental understanding of how the brain works. We will address them by studying a unique population of cells that is continually generated throughout life: dopaminergic neurons in the olfactory bulb. These cells play a key role in the modulation of early sensory responses and are renowned for their plastic capacity. However, the role of this plasticity in shaping sensory processing remains completely unknown. FUNCOPLAN’s first objectives, therefore, are to discover novel experience-dependent plastic changes in the cellular features and sensory response properties of adult-born neurons. We will then go much further than this, however, by integrating our discoveries with state-of-the-art techniques for precisely manipulating activity in these cells in vivo. This wholly innovative approach will allow us to mimic the effects of plasticity in naïve circuits, or cancel the effects of plasticity in experience-altered networks. In this way, we will break new ground, demonstrating a unique contribution of plasticity in adult-born cells to the fundamental function of neuronal circuitry.
Summary
The major objective of FUNCOPLAN is to examine groundbreaking questions on the functional role of newly-generated neurons in the adult brain. Using a combination of innovative approaches, our aim is to discover how plasticity in adult-born cells shapes information processing in neuronal circuits.
Adult neurogenesis produces new neurons in particular areas of the mammalian brain throughout life. Because they undergo a transient period of heightened plasticity, these freshly-generated cells are believed to bring unique properties to the circuits they join – a continual influx of new, immature cells is believed to provide a level of plasticity not achievable by the mature, resident network alone. But what exactly is the function of the additional plasticity provided by adult-born neurons? How does it influence information processing in neuronal networks?
These questions are vital for our fundamental understanding of how the brain works. We will address them by studying a unique population of cells that is continually generated throughout life: dopaminergic neurons in the olfactory bulb. These cells play a key role in the modulation of early sensory responses and are renowned for their plastic capacity. However, the role of this plasticity in shaping sensory processing remains completely unknown. FUNCOPLAN’s first objectives, therefore, are to discover novel experience-dependent plastic changes in the cellular features and sensory response properties of adult-born neurons. We will then go much further than this, however, by integrating our discoveries with state-of-the-art techniques for precisely manipulating activity in these cells in vivo. This wholly innovative approach will allow us to mimic the effects of plasticity in naïve circuits, or cancel the effects of plasticity in experience-altered networks. In this way, we will break new ground, demonstrating a unique contribution of plasticity in adult-born cells to the fundamental function of neuronal circuitry.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym HydroSync
Project Hydrodynamic Synchronisation in Model and Biological Systems
Researcher (PI) Pietro Cicuta
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Consolidator Grant (CoG), PE3, ERC-2013-CoG
Summary Cilia and flagella beating in synchronised patterns give rise to metachronal waves, beautiful examples of emergent behaviour in biology. These collective dynamical states are essential in life, transporting nutrients and clearing pathogens; they arise from the mechanical interaction of individual cilia mediated by the viscous fluid.
Severe pathologies are associated with cilia malfunction in humans. The current analysis of ciliated tissues in the clinic is focused purely on the frequency of beating: this is insufficient to discriminate between different pathologies. Much more information is present in the cilia dynamics video data that is recorded from patients; it is not being extracted because the correct theoretical framework for analysis is not in place.
We will develop our current work on actively driven colloidal systems to selectively test aspects of the biological scenarios, and start a new line of investigation in our lab, with cell culture experiments to validate these findings; we will understand the onset of collective dynamics (new physics), and how cilia waves are robust against fluctuations in cilia beat frequency, spatial arrangement and fluid rheology. New video analysis tools will be developed based on this full understanding of mechanical synchronisation, enabling the collective dynamics to be related back to the behaviour of individual cilia and to the physical properties of the fluid.
The team will be of two Post-docs, responsible for the two parts of the project: model and biological systems. A PhD student will contribute to the biological experiments, which present multiple lines of investigation, and will develop the video-analysis code to obtain the full degree of information from biological experiments.
The new analysis tool that results from this project will be deployed in the clinical setting through an established collaboration; enabling diagnosis of airway disorders represents a broad impact on physiology and clinical practice.
Summary
Cilia and flagella beating in synchronised patterns give rise to metachronal waves, beautiful examples of emergent behaviour in biology. These collective dynamical states are essential in life, transporting nutrients and clearing pathogens; they arise from the mechanical interaction of individual cilia mediated by the viscous fluid.
Severe pathologies are associated with cilia malfunction in humans. The current analysis of ciliated tissues in the clinic is focused purely on the frequency of beating: this is insufficient to discriminate between different pathologies. Much more information is present in the cilia dynamics video data that is recorded from patients; it is not being extracted because the correct theoretical framework for analysis is not in place.
We will develop our current work on actively driven colloidal systems to selectively test aspects of the biological scenarios, and start a new line of investigation in our lab, with cell culture experiments to validate these findings; we will understand the onset of collective dynamics (new physics), and how cilia waves are robust against fluctuations in cilia beat frequency, spatial arrangement and fluid rheology. New video analysis tools will be developed based on this full understanding of mechanical synchronisation, enabling the collective dynamics to be related back to the behaviour of individual cilia and to the physical properties of the fluid.
The team will be of two Post-docs, responsible for the two parts of the project: model and biological systems. A PhD student will contribute to the biological experiments, which present multiple lines of investigation, and will develop the video-analysis code to obtain the full degree of information from biological experiments.
The new analysis tool that results from this project will be deployed in the clinical setting through an established collaboration; enabling diagnosis of airway disorders represents a broad impact on physiology and clinical practice.
Max ERC Funding
1 261 572 €
Duration
Start date: 2014-05-01, End date: 2018-04-30
Project acronym IMBIBE
Project Innovative technology solutions to explore effects of the microbiome on intestine and brain pathophysiology
Researcher (PI) Róisín Meabh OWENS
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Consolidator Grant (CoG), PE7, ERC-2016-COG
Summary The human gut is host to over 100 trillion bacteria that are known to be essential for human health. Intestinal microbes can affect the function of the gastrointestinal (GI) tract, via immunity, nutrient absorption, energy metabolism and intestinal barrier function. Alterations in the microbiome have been linked with many disease phenotypes including colorectal cancer, Crohn’s disease, obesity, diabetes as well as neuropathologies such as autism spectrum disorder (ASD), stress and anxiety. Animal studies remain one of the sole means of assessing the importance of microbiota on development and well-being, however the use of animals to study human systems is increasingly questioned due to ethics, cost and relevance concerns. In vitro models have developed at an accelerated pace in the past decade, benefitting from advances in cell culture (in particular 3D cell culture and use of human cell types), increasing the viability of these systems as alternatives to traditional cell culture methods. This in turn will allow refinement and replacement of animal use. In particular in basic science, or high throughput approaches where animal models are under significant pressure to be replaced, in vitro human models can be singularly appropriate. The development of in vitro models with microbiota has not yet been demonstrated even though the transformative role of the microbiota appears unquestionable. The IMBIBE project will focus on using engineering and materials science approaches to develop complete (i.e. human and microbe) in vitro models to truly capture the human situation. IMBIBE will benefit from cutting edge organic electronic technology which will allow real-time monitoring thus enabling iterative improvements in the models employed. The result from this project will be a platform to study host-microbiome interactions and consequences for pathophysiology, in particular, of the GI tract and brain.
Summary
The human gut is host to over 100 trillion bacteria that are known to be essential for human health. Intestinal microbes can affect the function of the gastrointestinal (GI) tract, via immunity, nutrient absorption, energy metabolism and intestinal barrier function. Alterations in the microbiome have been linked with many disease phenotypes including colorectal cancer, Crohn’s disease, obesity, diabetes as well as neuropathologies such as autism spectrum disorder (ASD), stress and anxiety. Animal studies remain one of the sole means of assessing the importance of microbiota on development and well-being, however the use of animals to study human systems is increasingly questioned due to ethics, cost and relevance concerns. In vitro models have developed at an accelerated pace in the past decade, benefitting from advances in cell culture (in particular 3D cell culture and use of human cell types), increasing the viability of these systems as alternatives to traditional cell culture methods. This in turn will allow refinement and replacement of animal use. In particular in basic science, or high throughput approaches where animal models are under significant pressure to be replaced, in vitro human models can be singularly appropriate. The development of in vitro models with microbiota has not yet been demonstrated even though the transformative role of the microbiota appears unquestionable. The IMBIBE project will focus on using engineering and materials science approaches to develop complete (i.e. human and microbe) in vitro models to truly capture the human situation. IMBIBE will benefit from cutting edge organic electronic technology which will allow real-time monitoring thus enabling iterative improvements in the models employed. The result from this project will be a platform to study host-microbiome interactions and consequences for pathophysiology, in particular, of the GI tract and brain.
Max ERC Funding
1 992 578 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym IonDynDev
Project Ionic dynamics and plasticity in developing neuronal networks
Researcher (PI) Colin Jon Akerman
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary Ionic gradients are a fundamental feature of the nervous system and its development. They are established by the actions of ion pumps, transporters and channel proteins that reside in the membrane of cells. And maintaining these gradients is a prerequisite for generating fluxes of ions, which in turn drive cellular processes. Ion regulatory mechanisms often differ between cell types and changes in intracellular ion concentration have been implicated in multiple processes in the developing brain, from proliferation, to process outgrowth and the refinement of synaptic circuits. One of the limitations however, has been the shortage of experimental tools for dissecting intracellular ion dynamics in the developing nervous system. Here I propose to capitalise upon methods we have developed for directly measuring and manipulating ion concentrations in a spatially and temporally controlled manner. The proposal focuses upon two key ions: chloride ions and hydrogen ions, which can exhibit intracellular changes over a range of timescales. Working in the neocortex of developing mice, optical reporters will be used to measure ion dynamics at key stages of mammalian brain development and light-activated proteins will be used to selectively control intracellular ion levels. The first series of experiments will investigate chloride and hydrogen ion dynamics in neuronal progenitor cells and relate this to cellular processes during cortical neurogenesis. We will then compare how developing neurons and astrocytes establish their ion gradients, as our data indicate that these two cell types possess different regulatory mechanisms. We will examine how emerging network activity influences ion dynamics and then selectively manipulate these dynamics to examine their contribution to synaptic development and ongoing network activity. The final series of experiments will examine whether developing neurons show homeostatic responses when their intracellular ion gradients are challenged.
Summary
Ionic gradients are a fundamental feature of the nervous system and its development. They are established by the actions of ion pumps, transporters and channel proteins that reside in the membrane of cells. And maintaining these gradients is a prerequisite for generating fluxes of ions, which in turn drive cellular processes. Ion regulatory mechanisms often differ between cell types and changes in intracellular ion concentration have been implicated in multiple processes in the developing brain, from proliferation, to process outgrowth and the refinement of synaptic circuits. One of the limitations however, has been the shortage of experimental tools for dissecting intracellular ion dynamics in the developing nervous system. Here I propose to capitalise upon methods we have developed for directly measuring and manipulating ion concentrations in a spatially and temporally controlled manner. The proposal focuses upon two key ions: chloride ions and hydrogen ions, which can exhibit intracellular changes over a range of timescales. Working in the neocortex of developing mice, optical reporters will be used to measure ion dynamics at key stages of mammalian brain development and light-activated proteins will be used to selectively control intracellular ion levels. The first series of experiments will investigate chloride and hydrogen ion dynamics in neuronal progenitor cells and relate this to cellular processes during cortical neurogenesis. We will then compare how developing neurons and astrocytes establish their ion gradients, as our data indicate that these two cell types possess different regulatory mechanisms. We will examine how emerging network activity influences ion dynamics and then selectively manipulate these dynamics to examine their contribution to synaptic development and ongoing network activity. The final series of experiments will examine whether developing neurons show homeostatic responses when their intracellular ion gradients are challenged.
Max ERC Funding
1 689 631 €
Duration
Start date: 2015-02-01, End date: 2020-01-31
Project acronym IRIS
Project Infrared imaging and sensing: the single-photon frontier
Researcher (PI) Robert Hugh Hadfield
Host Institution (HI) UNIVERSITY OF GLASGOW
Call Details Consolidator Grant (CoG), PE7, ERC-2014-CoG
Summary Infrared sensing technology has a central role to play in addressing 21st century global challenges in healthcare, security and environmental sensing. Promising new applications hinge on the ability to detect individual quanta of light: single photons. At infrared wavelengths this is a formidable task due to the low photon energy, and commercial-off-the-shelf technologies fall far short of the required performance. IRIS will engineer revolutionary photon counting infrared imaging and sensing solutions, with unprecedented spectral range, efficiency, timing resolution and low noise. Using state-of-the-art materials and nanofabrication techniques, novel superconducting detector technology will be scaled up from single pixels to large area photon counting arrays. Efficient readout and optical coupling solutions will be developed and implemented. IRIS will exploit space age cryogenic technology to create compact and mobile detector systems. IRIS will deploy these systems for the first time in revolutionary infrared imaging and sensing applications: dosimetry for laser based cancer treatment, atmospheric remote sensing of greenhouse gases and real-time distributed fibre sensing for geothermal energy.
Summary
Infrared sensing technology has a central role to play in addressing 21st century global challenges in healthcare, security and environmental sensing. Promising new applications hinge on the ability to detect individual quanta of light: single photons. At infrared wavelengths this is a formidable task due to the low photon energy, and commercial-off-the-shelf technologies fall far short of the required performance. IRIS will engineer revolutionary photon counting infrared imaging and sensing solutions, with unprecedented spectral range, efficiency, timing resolution and low noise. Using state-of-the-art materials and nanofabrication techniques, novel superconducting detector technology will be scaled up from single pixels to large area photon counting arrays. Efficient readout and optical coupling solutions will be developed and implemented. IRIS will exploit space age cryogenic technology to create compact and mobile detector systems. IRIS will deploy these systems for the first time in revolutionary infrared imaging and sensing applications: dosimetry for laser based cancer treatment, atmospheric remote sensing of greenhouse gases and real-time distributed fibre sensing for geothermal energy.
Max ERC Funding
1 792 906 €
Duration
Start date: 2015-06-01, End date: 2019-11-30
Project acronym LeaRNN
Project Principles of Learning in a Recurrent Neural Network
Researcher (PI) Marta Zlatic
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary Forming memories, generating predictions based on memories, and updating memories when predictions no longer match actual experience are fundamental brain functions. Dopaminergic neurons provide a so-called “teaching signal” that drives the formation and updates of associative memories across the animal kingdom. Many theoretical models propose how neural circuits could compute the teaching signals, but the actual implementation of this computation in real nervous systems is unknown.
This project will discover the basic principles by which neural circuits compute the teaching signals that drive memory formation and updates using a tractable insect model system, the Drosophila larva. We will generate, for the first time in any animal, the following essential datasets for a distributed, multilayered, recurrent learning circuit, the mushroom body-related circuitry in the larval brain. First, building on our preliminary work that provides the synaptic-resolution connectome of the circuit, including all feedforward and feedback pathways upstream of all dopaminergic neurons, we will generate a map of functional monosynaptic connections. Second, we will obtain cellular-resolution whole-nervous system activity maps in intact living animals, as they form, extinguish, or consolidate memories to discover the features represented in each layer of the circuit (e.g. predictions, actual reinforcement, and prediction errors), the learning algorithms, and the candidate circuit motifs that implement them. Finally, we will develop a model of the circuit constrained by these datasets and test the predictions about the necessity and sufficiency of uniquely identified circuit elements for implementing learning algorithms by selectively manipulating their activity.
Understanding the basic functional principles of an entire multilayered recurrent learning circuit in an animal has the potential to revolutionize, not only neuroscience and medicine, but also machine-learning and robotics.
Summary
Forming memories, generating predictions based on memories, and updating memories when predictions no longer match actual experience are fundamental brain functions. Dopaminergic neurons provide a so-called “teaching signal” that drives the formation and updates of associative memories across the animal kingdom. Many theoretical models propose how neural circuits could compute the teaching signals, but the actual implementation of this computation in real nervous systems is unknown.
This project will discover the basic principles by which neural circuits compute the teaching signals that drive memory formation and updates using a tractable insect model system, the Drosophila larva. We will generate, for the first time in any animal, the following essential datasets for a distributed, multilayered, recurrent learning circuit, the mushroom body-related circuitry in the larval brain. First, building on our preliminary work that provides the synaptic-resolution connectome of the circuit, including all feedforward and feedback pathways upstream of all dopaminergic neurons, we will generate a map of functional monosynaptic connections. Second, we will obtain cellular-resolution whole-nervous system activity maps in intact living animals, as they form, extinguish, or consolidate memories to discover the features represented in each layer of the circuit (e.g. predictions, actual reinforcement, and prediction errors), the learning algorithms, and the candidate circuit motifs that implement them. Finally, we will develop a model of the circuit constrained by these datasets and test the predictions about the necessity and sufficiency of uniquely identified circuit elements for implementing learning algorithms by selectively manipulating their activity.
Understanding the basic functional principles of an entire multilayered recurrent learning circuit in an animal has the potential to revolutionize, not only neuroscience and medicine, but also machine-learning and robotics.
Max ERC Funding
2 350 000 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
