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 APOLLO
Project Advanced Signal Processing Technologies for Wireless Powered Communications
Researcher (PI) Ioannis Krikidis
Host Institution (HI) UNIVERSITY OF CYPRUS
Call Details Consolidator Grant (CoG), PE7, ERC-2018-COG
Summary Wireless power transfer (WPT), pioneered by Tesla, is an idea at least as old as radio communications. However, on the one hand, due to health concerns and the large antenna dimensions required for transmission of high energy levels, until recently WPT has been limited mostly to very short distance applications. On the other hand, recent advances in silicon technology have significantly reduced the energy needs of electronic systems, making WPT over radio waves a potential source of energy for low power devices. Although WPT through radio waves has already found various short-range applications (such as the radio-frequency identification technology, healthcare monitoring etc.), its integration as a building block in the operation of wireless communications systems is still unexploited. On the other hand, conventional radio wave based information and energy transmissions have largely been designed separately. However, many applications can benefit from simultaneous wireless information and power transfer (SWIPT).
The overall objective of the APOLLO project is to study the integration of WPT/SWIPT technology into future wireless communication systems. Compared to past and current research efforts in this area, our technical approach is deeply interdisciplinary and more comprehensive, combining the expertise of wireless communications, control theory, information theory, optimization, and electronics/microwave engineering.
The key outcomes of the project include: 1) a rigorous and complete mathematical theory for WPT/SWIPT via information/communication/control theoretic studies; 2) new physical and cross-layer mechanisms that will enable the integration of WPT/SWIPT into future communication systems; 3) new network architectures that will fully exploit potential benefits of WPT/SWIPT; and 4) development of a proof-of-concept by implementing highly-efficient and multi-band metamaterial energy harvesting sensors for SWIPT.
Summary
Wireless power transfer (WPT), pioneered by Tesla, is an idea at least as old as radio communications. However, on the one hand, due to health concerns and the large antenna dimensions required for transmission of high energy levels, until recently WPT has been limited mostly to very short distance applications. On the other hand, recent advances in silicon technology have significantly reduced the energy needs of electronic systems, making WPT over radio waves a potential source of energy for low power devices. Although WPT through radio waves has already found various short-range applications (such as the radio-frequency identification technology, healthcare monitoring etc.), its integration as a building block in the operation of wireless communications systems is still unexploited. On the other hand, conventional radio wave based information and energy transmissions have largely been designed separately. However, many applications can benefit from simultaneous wireless information and power transfer (SWIPT).
The overall objective of the APOLLO project is to study the integration of WPT/SWIPT technology into future wireless communication systems. Compared to past and current research efforts in this area, our technical approach is deeply interdisciplinary and more comprehensive, combining the expertise of wireless communications, control theory, information theory, optimization, and electronics/microwave engineering.
The key outcomes of the project include: 1) a rigorous and complete mathematical theory for WPT/SWIPT via information/communication/control theoretic studies; 2) new physical and cross-layer mechanisms that will enable the integration of WPT/SWIPT into future communication systems; 3) new network architectures that will fully exploit potential benefits of WPT/SWIPT; and 4) development of a proof-of-concept by implementing highly-efficient and multi-band metamaterial energy harvesting sensors for SWIPT.
Max ERC Funding
1 930 625 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
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 DarkComb
Project Dark-Soliton Engineering in Microresonator Frequency Combs
Researcher (PI) Victor TORRES COMPANY
Host Institution (HI) CHALMERS TEKNISKA HOEGSKOLA AB
Call Details Consolidator Grant (CoG), PE7, ERC-2017-COG
Summary The continuing increase in Internet data traffic is pushing the capacity of single-mode fiber to its fundamental limits. Space division multiplexing (SDM) offers the only remaining physical degree of freedom – the space dimension in the transmission channel – to substantially increase the capacity in lightwave communication systems.
The microresonator comb is an emerging technology platform that enables the generation of an optical frequency comb in a micrometer-scale cavity. Its compact size and compatibility with established semiconductor fabrication techniques promises to revolutionize the fields of frequency synthesis and metrology, and create new mass-market applications.
I envision significant scaling advantages in future fiber-optic communications by merging SDM with microresonator frequency combs. One major obstacle to overcome here is the poor conversion efficiency that can be fundamentally obtained using the most stable and broadest combs generated in microresonators today. I propose to look into the generation of dark, as opposed to bright, temporal solitons in linearly coupled microresonators. The goal is to achieve reliable microresonator combs with exceptionally high power conversion efficiency, resulting in optimal characteristics for SDM applications. The scientific and technological possibilities of this achievement promise significant impact beyond the realm of fiber-optic communications.
My broad international experience, unique background in fiber communications, photonic waveguides and ultrafast photonics, the preliminary results of my group and the available infrastructure at my university place me in an outstanding position to pioneer this new direction of research.
Summary
The continuing increase in Internet data traffic is pushing the capacity of single-mode fiber to its fundamental limits. Space division multiplexing (SDM) offers the only remaining physical degree of freedom – the space dimension in the transmission channel – to substantially increase the capacity in lightwave communication systems.
The microresonator comb is an emerging technology platform that enables the generation of an optical frequency comb in a micrometer-scale cavity. Its compact size and compatibility with established semiconductor fabrication techniques promises to revolutionize the fields of frequency synthesis and metrology, and create new mass-market applications.
I envision significant scaling advantages in future fiber-optic communications by merging SDM with microresonator frequency combs. One major obstacle to overcome here is the poor conversion efficiency that can be fundamentally obtained using the most stable and broadest combs generated in microresonators today. I propose to look into the generation of dark, as opposed to bright, temporal solitons in linearly coupled microresonators. The goal is to achieve reliable microresonator combs with exceptionally high power conversion efficiency, resulting in optimal characteristics for SDM applications. The scientific and technological possibilities of this achievement promise significant impact beyond the realm of fiber-optic communications.
My broad international experience, unique background in fiber communications, photonic waveguides and ultrafast photonics, the preliminary results of my group and the available infrastructure at my university place me in an outstanding position to pioneer this new direction of research.
Max ERC Funding
2 259 523 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
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 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 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
