Project acronym 4D-GenEx
Project Spatio-temporal Organization and Expression of the Genome
Researcher (PI) Antoine COULON
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), LS2, ERC-2017-STG
Summary This project investigates the two-way relationship between spatio-temporal genome organization and coordinated gene regulation, through an approach at the interface between physics, computer science and biology.
In the nucleus, preferred positions are observed from chromosomes to single genes, in relation to normal and pathological cellular states. Evidence indicates a complex spatio-temporal coupling between co-regulated genes: e.g. certain genes cluster spatially when responding to similar factors and transcriptional noise patterns suggest domain-wide mechanisms. Yet, no individual experiment allows probing transcriptional coordination in 4 dimensions (FISH, live locus tracking, Hi-C...). Interpreting such data also critically requires theory (stochastic processes, statistical physics…). A lack of appropriate experimental/analytical approaches is impairing our understanding of the 4D genome.
Our proposal combines cutting-edge single-molecule imaging, signal-theory data analysis and physical modeling to study how genes coordinate in space and time in a single nucleus. Our objectives are to understand (a) competition/recycling of shared resources between genes within subnuclear compartments, (b) how enhancers communicate with genes domain-wide, and (c) the role of local conformational dynamics and supercoiling in gene co-regulation. Our organizing hypothesis is that, by acting on their microenvironment, genes shape their co-expression with other genes.
Building upon my expertise, we will use dual-color MS2/PP7 RNA labeling to visualize for the first time transcription and motion of pairs of hormone-responsive genes in real time. With our innovative signal analysis tools, we will extract spatio-temporal signatures of underlying processes, which we will investigate with stochastic modeling and validate through experimental perturbations. We expect to uncover how the functional organization of the linear genome relates to its physical properties and dynamics in 4D.
Summary
This project investigates the two-way relationship between spatio-temporal genome organization and coordinated gene regulation, through an approach at the interface between physics, computer science and biology.
In the nucleus, preferred positions are observed from chromosomes to single genes, in relation to normal and pathological cellular states. Evidence indicates a complex spatio-temporal coupling between co-regulated genes: e.g. certain genes cluster spatially when responding to similar factors and transcriptional noise patterns suggest domain-wide mechanisms. Yet, no individual experiment allows probing transcriptional coordination in 4 dimensions (FISH, live locus tracking, Hi-C...). Interpreting such data also critically requires theory (stochastic processes, statistical physics…). A lack of appropriate experimental/analytical approaches is impairing our understanding of the 4D genome.
Our proposal combines cutting-edge single-molecule imaging, signal-theory data analysis and physical modeling to study how genes coordinate in space and time in a single nucleus. Our objectives are to understand (a) competition/recycling of shared resources between genes within subnuclear compartments, (b) how enhancers communicate with genes domain-wide, and (c) the role of local conformational dynamics and supercoiling in gene co-regulation. Our organizing hypothesis is that, by acting on their microenvironment, genes shape their co-expression with other genes.
Building upon my expertise, we will use dual-color MS2/PP7 RNA labeling to visualize for the first time transcription and motion of pairs of hormone-responsive genes in real time. With our innovative signal analysis tools, we will extract spatio-temporal signatures of underlying processes, which we will investigate with stochastic modeling and validate through experimental perturbations. We expect to uncover how the functional organization of the linear genome relates to its physical properties and dynamics in 4D.
Max ERC Funding
1 499 750 €
Duration
Start date: 2018-04-01, End date: 2023-03-31
Project acronym 5D-NanoTrack
Project Five-Dimensional Localization Microscopy for Sub-Cellular Dynamics
Researcher (PI) Yoav SHECHTMAN
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), PE7, ERC-2018-STG
Summary The sub-cellular processes that control the most critical aspects of life occur in three-dimensions (3D), and are intrinsically dynamic. While super-resolution microscopy has revolutionized cellular imaging in recent years, our current capability to observe the dynamics of life on the nanoscale is still extremely limited, due to inherent trade-offs between spatial, temporal and spectral resolution using existing approaches.
We propose to develop and demonstrate an optical microscopy methodology that would enable live sub-cellular observation in unprecedented detail. Making use of multicolor 3D point-spread-function (PSF) engineering, a technique I have recently developed, we will be able to simultaneously track multiple markers inside live cells, at high speed and in five-dimensions (3D, time, and color).
Multicolor 3D PSF engineering holds the potential of being a uniquely powerful method for 5D tracking. However, it is not yet applicable to live-cell imaging, due to significant bottlenecks in optical engineering and signal processing, which we plan to overcome in this project. Importantly, we will also demonstrate the efficacy of our method using a challenging biological application: real-time visualization of chromatin dynamics - the spatiotemporal organization of DNA. This is a highly suitable problem due to its fundamental importance, its role in a variety of cellular processes, and the lack of appropriate tools for studying it.
The project is divided into 3 aims:
1. Technology development: diffractive-element design for multicolor 3D PSFs.
2. System design: volumetric tracking of dense emitters.
3. Live-cell measurements: chromatin dynamics.
Looking ahead, here we create the imaging tools that pave the way towards the holy grail of chromatin visualization: dynamic observation of the 3D positions of the ~3 billion DNA base-pairs in a live human cell. Beyond that, our results will be applicable to numerous 3D micro/nanoscale tracking applications.
Summary
The sub-cellular processes that control the most critical aspects of life occur in three-dimensions (3D), and are intrinsically dynamic. While super-resolution microscopy has revolutionized cellular imaging in recent years, our current capability to observe the dynamics of life on the nanoscale is still extremely limited, due to inherent trade-offs between spatial, temporal and spectral resolution using existing approaches.
We propose to develop and demonstrate an optical microscopy methodology that would enable live sub-cellular observation in unprecedented detail. Making use of multicolor 3D point-spread-function (PSF) engineering, a technique I have recently developed, we will be able to simultaneously track multiple markers inside live cells, at high speed and in five-dimensions (3D, time, and color).
Multicolor 3D PSF engineering holds the potential of being a uniquely powerful method for 5D tracking. However, it is not yet applicable to live-cell imaging, due to significant bottlenecks in optical engineering and signal processing, which we plan to overcome in this project. Importantly, we will also demonstrate the efficacy of our method using a challenging biological application: real-time visualization of chromatin dynamics - the spatiotemporal organization of DNA. This is a highly suitable problem due to its fundamental importance, its role in a variety of cellular processes, and the lack of appropriate tools for studying it.
The project is divided into 3 aims:
1. Technology development: diffractive-element design for multicolor 3D PSFs.
2. System design: volumetric tracking of dense emitters.
3. Live-cell measurements: chromatin dynamics.
Looking ahead, here we create the imaging tools that pave the way towards the holy grail of chromatin visualization: dynamic observation of the 3D positions of the ~3 billion DNA base-pairs in a live human cell. Beyond that, our results will be applicable to numerous 3D micro/nanoscale tracking applications.
Max ERC Funding
1 802 500 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym ACrossWire
Project A Cross-Correlated Approach to Engineering Nitride Nanowires
Researcher (PI) Hannah Jane JOYCE
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), PE7, ERC-2016-STG
Summary Nanowires based on group III–nitride semiconductors exhibit outstanding potential for emerging applications in energy-efficient lighting, optoelectronics and solar energy harvesting. Nitride nanowires, tailored at the nanoscale, should overcome many of the challenges facing conventional planar nitride materials, and also add extraordinary new functionality to these materials. However, progress towards III–nitride nanowire devices has been hampered by the challenges in quantifying nanowire electrical properties using conventional contact-based measurements. Without reliable electrical transport data, it is extremely difficult to optimise nanowire growth and device design. This project aims to overcome this problem through an unconventional approach: advanced contact-free electrical measurements. Contact-free measurements, growth studies, and device studies will be cross-correlated to provide unprecedented insight into the growth mechanisms that govern nanowire electronic properties and ultimately dictate device performance. A key contact-free technique at the heart of this proposal is ultrafast terahertz conductivity spectroscopy: an advanced technique ideal for probing nanowire electrical properties. We will develop new methods to enable the full suite of contact-free (including terahertz, photoluminescence and cathodoluminescence measurements) and contact-based measurements to be performed with high spatial resolution on the same nanowires. This will provide accurate, comprehensive and cross-correlated feedback to guide growth studies and expedite the targeted development of nanowires with specified functionality. We will apply this powerful approach to tailor nanowires as photoelectrodes for solar photoelectrochemical water splitting. This is an application for which nitride nanowires have outstanding, yet unfulfilled, potential. This project will thus harness the true potential of nitride nanowires and bring them to the forefront of 21st century technology.
Summary
Nanowires based on group III–nitride semiconductors exhibit outstanding potential for emerging applications in energy-efficient lighting, optoelectronics and solar energy harvesting. Nitride nanowires, tailored at the nanoscale, should overcome many of the challenges facing conventional planar nitride materials, and also add extraordinary new functionality to these materials. However, progress towards III–nitride nanowire devices has been hampered by the challenges in quantifying nanowire electrical properties using conventional contact-based measurements. Without reliable electrical transport data, it is extremely difficult to optimise nanowire growth and device design. This project aims to overcome this problem through an unconventional approach: advanced contact-free electrical measurements. Contact-free measurements, growth studies, and device studies will be cross-correlated to provide unprecedented insight into the growth mechanisms that govern nanowire electronic properties and ultimately dictate device performance. A key contact-free technique at the heart of this proposal is ultrafast terahertz conductivity spectroscopy: an advanced technique ideal for probing nanowire electrical properties. We will develop new methods to enable the full suite of contact-free (including terahertz, photoluminescence and cathodoluminescence measurements) and contact-based measurements to be performed with high spatial resolution on the same nanowires. This will provide accurate, comprehensive and cross-correlated feedback to guide growth studies and expedite the targeted development of nanowires with specified functionality. We will apply this powerful approach to tailor nanowires as photoelectrodes for solar photoelectrochemical water splitting. This is an application for which nitride nanowires have outstanding, yet unfulfilled, potential. This project will thus harness the true potential of nitride nanowires and bring them to the forefront of 21st century technology.
Max ERC Funding
1 499 195 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym ANOREP
Project Targeting the reproductive biology of the malaria mosquito Anopheles gambiae: from laboratory studies to field applications
Researcher (PI) Flaminia Catteruccia
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PERUGIA
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary Anopheles gambiae mosquitoes are the major vectors of malaria, a disease with devastating consequences for
human health. Novel methods for controlling the natural vector populations are urgently needed, given the
evolution of insecticide resistance in mosquitoes and the lack of novel insecticidals. Understanding the
processes at the bases of mosquito biology may help to roll back malaria. In this proposal, we will target
mosquito reproduction, a major determinant of the An. gambiae vectorial capacity. This will be achieved at
two levels: (i) fundamental research, to provide a deeper knowledge of the processes regulating reproduction
in this species, and (ii) applied research, to identify novel targets and to develop innovative approaches for
the control of natural populations. We will focus our analysis on three major players of mosquito
reproduction: male accessory glands (MAGs), sperm, and spermatheca, in both laboratory and field settings.
We will then translate this information into the identification of inhibitors of mosquito fertility. The
experimental activities will be divided across three objectives. In Objective 1, we will unravel the role of the
MAGs in shaping mosquito fertility and behaviour, by performing a combination of transcriptional and
functional studies that will reveal the multifaceted activities of these tissues. In Objective 2 we will instead
focus on the identification of the male and female factors responsible for sperm viability and function.
Results obtained in both objectives will be validated in field mosquitoes. In Objective 3, we will perform
screens aimed at the identification of inhibitors of mosquito reproductive success. This study will reveal as
yet unknown molecular mechanisms underlying reproductive success in mosquitoes, considerably increasing
our knowledge beyond the state-of-the-art and critically contributing with innovative tools and ideas to the
fight against malaria.
Summary
Anopheles gambiae mosquitoes are the major vectors of malaria, a disease with devastating consequences for
human health. Novel methods for controlling the natural vector populations are urgently needed, given the
evolution of insecticide resistance in mosquitoes and the lack of novel insecticidals. Understanding the
processes at the bases of mosquito biology may help to roll back malaria. In this proposal, we will target
mosquito reproduction, a major determinant of the An. gambiae vectorial capacity. This will be achieved at
two levels: (i) fundamental research, to provide a deeper knowledge of the processes regulating reproduction
in this species, and (ii) applied research, to identify novel targets and to develop innovative approaches for
the control of natural populations. We will focus our analysis on three major players of mosquito
reproduction: male accessory glands (MAGs), sperm, and spermatheca, in both laboratory and field settings.
We will then translate this information into the identification of inhibitors of mosquito fertility. The
experimental activities will be divided across three objectives. In Objective 1, we will unravel the role of the
MAGs in shaping mosquito fertility and behaviour, by performing a combination of transcriptional and
functional studies that will reveal the multifaceted activities of these tissues. In Objective 2 we will instead
focus on the identification of the male and female factors responsible for sperm viability and function.
Results obtained in both objectives will be validated in field mosquitoes. In Objective 3, we will perform
screens aimed at the identification of inhibitors of mosquito reproductive success. This study will reveal as
yet unknown molecular mechanisms underlying reproductive success in mosquitoes, considerably increasing
our knowledge beyond the state-of-the-art and critically contributing with innovative tools and ideas to the
fight against malaria.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym BEACON
Project Hybrid Digital-Analog Networking under Extreme Energy and Latency Constraints
Researcher (PI) Deniz Gunduz
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Starting Grant (StG), PE7, ERC-2015-STG
Summary The objective of the BEACON project is to (re-)introduce analog communications into the design of modern wireless networks. We argue that the extreme energy and latency constraints imposed by the emerging Internet of Everything (IoE) paradigm can only be met within a hybrid digital-analog communications framework. Current network architectures separate source and channel coding, orthogonalize users, and employ long block-length digital source and channel codes, which are either suboptimal or not applicable under the aforementioned constraints. BEACON questions these well-established design principles, and proposes to replace them with a hybrid digital-analog communications framework, which will meet the required energy and latency constraints while simplifying the encoding and decoding processes. BEACON pushes the performance of the IoE to its theoretical limits by i) exploiting signal correlations that are abundant in IoE applications, given the foreseen density of deployed sensing devices, ii) taking into account the limited and stochastic nature of energy availability due to, for example, energy harvesting capabilities, iii) using feedback resources to improve the end-to-end signal distortion, and iv) deriving novel converse results to identify fundamental performance benchmarks.
The results of BEACON will not only shed light on the fundamental limits on the performance any coding scheme can achieve, but will also lead to the development of unconventional codes and communication protocols that can approach these limits, combining digital and analog communication techniques. The ultimate challenge for this project is to exploit the developed hybrid digital-analog networking theory for a complete overhaul of the physical layer design for emerging IoE applications, such as smart grids, tele-robotics and smart homes. For this purpose, a proof-of-concept implementation test-bed will also be built using software defined radios and sensor nodes.
Summary
The objective of the BEACON project is to (re-)introduce analog communications into the design of modern wireless networks. We argue that the extreme energy and latency constraints imposed by the emerging Internet of Everything (IoE) paradigm can only be met within a hybrid digital-analog communications framework. Current network architectures separate source and channel coding, orthogonalize users, and employ long block-length digital source and channel codes, which are either suboptimal or not applicable under the aforementioned constraints. BEACON questions these well-established design principles, and proposes to replace them with a hybrid digital-analog communications framework, which will meet the required energy and latency constraints while simplifying the encoding and decoding processes. BEACON pushes the performance of the IoE to its theoretical limits by i) exploiting signal correlations that are abundant in IoE applications, given the foreseen density of deployed sensing devices, ii) taking into account the limited and stochastic nature of energy availability due to, for example, energy harvesting capabilities, iii) using feedback resources to improve the end-to-end signal distortion, and iv) deriving novel converse results to identify fundamental performance benchmarks.
The results of BEACON will not only shed light on the fundamental limits on the performance any coding scheme can achieve, but will also lead to the development of unconventional codes and communication protocols that can approach these limits, combining digital and analog communication techniques. The ultimate challenge for this project is to exploit the developed hybrid digital-analog networking theory for a complete overhaul of the physical layer design for emerging IoE applications, such as smart grids, tele-robotics and smart homes. For this purpose, a proof-of-concept implementation test-bed will also be built using software defined radios and sensor nodes.
Max ERC Funding
1 496 350 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym BIOSYNCEN
Project Dissection of centromeric chromatin and components: A biosynthetic approach
Researcher (PI) Patrick Heun
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Call Details Starting Grant (StG), LS2, ERC-2012-StG_20111109
Summary The centromere is one of the most important chromosomal elements. It is required for proper chromosome segregation in mitosis and meiosis and readily recognizable as the primary constriction of mitotic chromosomes. Proper centromere function is essential to ensure genome stability; therefore understanding centromere identity is directly relevant to cancer biology and gene therapy. How centromeres are established and maintained is however still an open question in the field. In most organisms this appears to be regulated by an epigenetic mechanism. The key candidate for such an epigenetic mark is CENH3 (CENP-A in mammals, CID in Drosophila), a centromere-specific histone H3 variant that is essential for centromere function and exclusively found in the nucleosomes of centromeric chromatin. Using a biosynthetic approach of force-targeting CENH3 in Drosophila to non-centromeric DNA, we were able to induce centromere function and demonstrate that CENH3 is sufficient to determine centromere identity. Here we propose to move this experimental setup across evolutionary boundaries into human cells to develop improved human artificial chromosomes (HACs). We will make further use of this unique setup to dissect the function of targeted CENH3 both in Drosophila and human cells. Contributing centromeric components and histone modifications of centromeric chromatin will be characterized in detail by mass spectroscopy in Drosophila. Finally we are proposing to develop a technique that allows high-resolution mapping of proteins on repetitive DNA to help further characterizing known and novel centromere components. This will be achieved by combining two independently established techniques: DNA methylation and DNA fiber combing. This ambitious proposal will significantly advance our understanding of how centromeres are determined and help the development of improved HACs for therapeutic applications in the future.
Summary
The centromere is one of the most important chromosomal elements. It is required for proper chromosome segregation in mitosis and meiosis and readily recognizable as the primary constriction of mitotic chromosomes. Proper centromere function is essential to ensure genome stability; therefore understanding centromere identity is directly relevant to cancer biology and gene therapy. How centromeres are established and maintained is however still an open question in the field. In most organisms this appears to be regulated by an epigenetic mechanism. The key candidate for such an epigenetic mark is CENH3 (CENP-A in mammals, CID in Drosophila), a centromere-specific histone H3 variant that is essential for centromere function and exclusively found in the nucleosomes of centromeric chromatin. Using a biosynthetic approach of force-targeting CENH3 in Drosophila to non-centromeric DNA, we were able to induce centromere function and demonstrate that CENH3 is sufficient to determine centromere identity. Here we propose to move this experimental setup across evolutionary boundaries into human cells to develop improved human artificial chromosomes (HACs). We will make further use of this unique setup to dissect the function of targeted CENH3 both in Drosophila and human cells. Contributing centromeric components and histone modifications of centromeric chromatin will be characterized in detail by mass spectroscopy in Drosophila. Finally we are proposing to develop a technique that allows high-resolution mapping of proteins on repetitive DNA to help further characterizing known and novel centromere components. This will be achieved by combining two independently established techniques: DNA methylation and DNA fiber combing. This ambitious proposal will significantly advance our understanding of how centromeres are determined and help the development of improved HACs for therapeutic applications in the future.
Max ERC Funding
1 755 960 €
Duration
Start date: 2013-02-01, End date: 2019-01-31
Project acronym blackQD
Project Optoelectronic of narrow band gap nanocrystals
Researcher (PI) Emmanuel LHUILLIER
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE7, ERC-2017-STG
Summary Over the past decades, silicon became the most used material for electronic, however its indirect band gap limits its use for optics and optoelectronics. As a result alternatives semiconductor such as III-V and II-VI materials are used to address a broad range of complementary application such as LED, laser diode and photodiode. However in the infrared (IR), the material challenge becomes far more complex.
New IR applications, such as flame detection or night car driving assistance are emerging and request low cost detectors. Current technologies, based on epitaxially grown semiconductors are unlikely to bring a cost disruption and organic electronics, often viewed as the alternative to silicon based materials is ineffective in the mid-IR. The blackQD project aims at transforming colloidal quantum dots (CQD) into the next generation of active material for IR detection. CQD are attracting a high interest because of their size tunable optical features and next challenges is their integration in optoelectronic devices and in particular for IR features.
The project requires a combination of material knowledge, with clean room nanofabrication and IR photoconduction which is unique in Europe. I organize blackQD in three mains parts. The first part relates to the growth of mercury chalcogenides nanocrystals with unique tunable properties in the mid and far-IR. To design devices with enhanced properties, more needs to be known on the electronic structure of these nanomaterials. In part II, I propose to develop original methods to probe static and dynamic aspects of the electronic structure. Finally the main task of the project relates to the design of a new generation of transistors and IR detectors. I propose several geometries of demonstrator which for the first time integrate from the beginning the colloidal nature of the CQD and constrain of IR photodetection. The project more generally aims to develop a tool box for the design of the next generation of low cost IR.
Summary
Over the past decades, silicon became the most used material for electronic, however its indirect band gap limits its use for optics and optoelectronics. As a result alternatives semiconductor such as III-V and II-VI materials are used to address a broad range of complementary application such as LED, laser diode and photodiode. However in the infrared (IR), the material challenge becomes far more complex.
New IR applications, such as flame detection or night car driving assistance are emerging and request low cost detectors. Current technologies, based on epitaxially grown semiconductors are unlikely to bring a cost disruption and organic electronics, often viewed as the alternative to silicon based materials is ineffective in the mid-IR. The blackQD project aims at transforming colloidal quantum dots (CQD) into the next generation of active material for IR detection. CQD are attracting a high interest because of their size tunable optical features and next challenges is their integration in optoelectronic devices and in particular for IR features.
The project requires a combination of material knowledge, with clean room nanofabrication and IR photoconduction which is unique in Europe. I organize blackQD in three mains parts. The first part relates to the growth of mercury chalcogenides nanocrystals with unique tunable properties in the mid and far-IR. To design devices with enhanced properties, more needs to be known on the electronic structure of these nanomaterials. In part II, I propose to develop original methods to probe static and dynamic aspects of the electronic structure. Finally the main task of the project relates to the design of a new generation of transistors and IR detectors. I propose several geometries of demonstrator which for the first time integrate from the beginning the colloidal nature of the CQD and constrain of IR photodetection. The project more generally aims to develop a tool box for the design of the next generation of low cost IR.
Max ERC Funding
1 499 903 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym BrainConquest
Project Boosting Brain-Computer Communication with high Quality User Training
Researcher (PI) Fabien LOTTE
Host Institution (HI) INSTITUT NATIONAL DE RECHERCHE ENINFORMATIQUE ET AUTOMATIQUE
Call Details Starting Grant (StG), PE7, ERC-2016-STG
Summary Brain-Computer Interfaces (BCIs) are communication systems that enable users to send commands to computers through brain signals only, by measuring and processing these signals. Making computer control possible without any physical activity, BCIs have promised to revolutionize many application areas, notably assistive technologies, e.g., for wheelchair control, and human-machine interaction. Despite this promising potential, BCIs are still barely used outside laboratories, due to their current poor reliability. For instance, BCIs only using two imagined hand movements as mental commands decode, on average, less than 80% of these commands correctly, while 10 to 30% of users cannot control a BCI at all.
A BCI should be considered a co-adaptive communication system: its users learn to encode commands in their brain signals (with mental imagery) that the machine learns to decode using signal processing. Most research efforts so far have been dedicated to decoding the commands. However, BCI control is a skill that users have to learn too. Unfortunately how BCI users learn to encode the commands is essential but is barely studied, i.e., fundamental knowledge about how users learn BCI control is lacking. Moreover standard training approaches are only based on heuristics, without satisfying human learning principles. Thus, poor BCI reliability is probably largely due to highly suboptimal user training.
In order to obtain a truly reliable BCI we need to completely redefine user training approaches. To do so, I propose to study and statistically model how users learn to encode BCI commands. Then, based on human learning principles and this model, I propose to create a new generation of BCIs which ensure that users learn how to successfully encode commands with high signal-to-noise ratio in their brain signals, hence making BCIs dramatically more reliable. Such a reliable BCI could positively change human-machine interaction as BCIs have promised but failed to do so far.
Summary
Brain-Computer Interfaces (BCIs) are communication systems that enable users to send commands to computers through brain signals only, by measuring and processing these signals. Making computer control possible without any physical activity, BCIs have promised to revolutionize many application areas, notably assistive technologies, e.g., for wheelchair control, and human-machine interaction. Despite this promising potential, BCIs are still barely used outside laboratories, due to their current poor reliability. For instance, BCIs only using two imagined hand movements as mental commands decode, on average, less than 80% of these commands correctly, while 10 to 30% of users cannot control a BCI at all.
A BCI should be considered a co-adaptive communication system: its users learn to encode commands in their brain signals (with mental imagery) that the machine learns to decode using signal processing. Most research efforts so far have been dedicated to decoding the commands. However, BCI control is a skill that users have to learn too. Unfortunately how BCI users learn to encode the commands is essential but is barely studied, i.e., fundamental knowledge about how users learn BCI control is lacking. Moreover standard training approaches are only based on heuristics, without satisfying human learning principles. Thus, poor BCI reliability is probably largely due to highly suboptimal user training.
In order to obtain a truly reliable BCI we need to completely redefine user training approaches. To do so, I propose to study and statistically model how users learn to encode BCI commands. Then, based on human learning principles and this model, I propose to create a new generation of BCIs which ensure that users learn how to successfully encode commands with high signal-to-noise ratio in their brain signals, hence making BCIs dramatically more reliable. Such a reliable BCI could positively change human-machine interaction as BCIs have promised but failed to do so far.
Max ERC Funding
1 498 751 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym CancerFluxome
Project Cancer Cellular Metabolism across Space and Time
Researcher (PI) Tomer Shlomi
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), LS2, ERC-2016-STG
Summary The metabolism of cancer cells is altered to meet cellular requirements for growth, providing novel means to selectively target tumorigenesis. While extensively studied, our current view of cancer cellular metabolism is fundamentally limited by lack of information on variability in metabolic activity between distinct subcellular compartments and cells.
We propose to develop a spatio-temporal fluxomics approach for quantifying metabolic fluxes in the cytoplasm vs. mitochondria as well as their cell-cycle dynamics, combining mass-spectrometry based isotope tracing with cell synchronization, rapid cellular fractionation, and computational metabolic network modelling.
Spatio-temporal fluxomics will be used to revisit and challenge our current understanding of central metabolism and its induced adaptation to oncogenic events – an important endeavour considering that mitochondrial bioenergetics and biosynthesis are required for tumorigenesis and accumulating evidences for metabolic alterations throughout the cell-cycle.
Our preliminary results show intriguing oscillations between oxidative and reductive TCA cycle flux throughout the cell-cycle. We will explore the extent to which cells adapt their metabolism to fulfil the changing energetic and anabolic demands throughout the cell-cycle, how metabolic oscillations are regulated, and their benefit to cells in terms of thermodynamic efficiency. Spatial flux analysis will be instrumental for investigating glutaminolysis - a ‘hallmark’ metabolic adaptation in cancer involving shuttling of metabolic intermediates and cofactors between mitochondria and cytoplasm.
On a clinical front, our spatio-temporal fluxomics analysis will enable to disentangle oncogene-induced flux alterations, having an important tumorigenic role, from artefacts originating from population averaging. A comprehensive view of how cells adapt their metabolism due to oncogenic mutations will reveal novel targets for anti-cancer drugs.
Summary
The metabolism of cancer cells is altered to meet cellular requirements for growth, providing novel means to selectively target tumorigenesis. While extensively studied, our current view of cancer cellular metabolism is fundamentally limited by lack of information on variability in metabolic activity between distinct subcellular compartments and cells.
We propose to develop a spatio-temporal fluxomics approach for quantifying metabolic fluxes in the cytoplasm vs. mitochondria as well as their cell-cycle dynamics, combining mass-spectrometry based isotope tracing with cell synchronization, rapid cellular fractionation, and computational metabolic network modelling.
Spatio-temporal fluxomics will be used to revisit and challenge our current understanding of central metabolism and its induced adaptation to oncogenic events – an important endeavour considering that mitochondrial bioenergetics and biosynthesis are required for tumorigenesis and accumulating evidences for metabolic alterations throughout the cell-cycle.
Our preliminary results show intriguing oscillations between oxidative and reductive TCA cycle flux throughout the cell-cycle. We will explore the extent to which cells adapt their metabolism to fulfil the changing energetic and anabolic demands throughout the cell-cycle, how metabolic oscillations are regulated, and their benefit to cells in terms of thermodynamic efficiency. Spatial flux analysis will be instrumental for investigating glutaminolysis - a ‘hallmark’ metabolic adaptation in cancer involving shuttling of metabolic intermediates and cofactors between mitochondria and cytoplasm.
On a clinical front, our spatio-temporal fluxomics analysis will enable to disentangle oncogene-induced flux alterations, having an important tumorigenic role, from artefacts originating from population averaging. A comprehensive view of how cells adapt their metabolism due to oncogenic mutations will reveal novel targets for anti-cancer drugs.
Max ERC Funding
1 481 250 €
Duration
Start date: 2017-02-01, End date: 2022-01-31
Project acronym CDNF
Project Compartmentalization and dynamics of Nuclear functions
Researcher (PI) Angela Taddei
Host Institution (HI) INSTITUT CURIE
Call Details Starting Grant (StG), LS2, ERC-2007-StG
Summary The eukaryotic genome is packaged into large-scale chromatin structures that occupy distinct domains in the nucleus and this organization is now seen as a key contributor to genome functions. Two key functions of the genome can take advantage of nuclear organization: regulated gene expression and the propagation of a stable genome. To understand these fundamental processes, we have chosen to use yeast as a model system that allows genetics, molecular biology and advanced live microscopy approaches to be combined. Budding yeast have been very powerful to demonstrate that gene position can play an active role in regulating gene expression. Distinct subcompartments dedicated to either gene silencing or activation of specific genes are positioned at the nuclear periphery. To gain insight into the mechanisms underlying this sub-compartmentalization, we will address three complementary issues: - What are the mechanisms involved in the establishment and maintenance of silent nuclear compartments? - How and why are some activated genes recruited to the nuclear periphery? - What are the relationships between repressive and activating nuclear compartments? Concerning the maintenance of genome integrity, recent advances in yeast highlight the importance of nuclear architecture. However, how nuclear organization influences the formation and processing of DNA lesions remain poorly understood. We will focus on two main questions: - How and where in the nucleus are double strand breaks recognized, processed, and repaired? - Where do breaks or gaps resulting from replicative stress at 'fragile sites' arise in the nucleus and how does nuclear organization influence their stability? We hope to gain a better understanding of the mechanisms presiding nuclear organization and its importance for genome functions. These mechanisms are likely to be conserved and will be subsequently tested in higher eukaryotic cells.
Summary
The eukaryotic genome is packaged into large-scale chromatin structures that occupy distinct domains in the nucleus and this organization is now seen as a key contributor to genome functions. Two key functions of the genome can take advantage of nuclear organization: regulated gene expression and the propagation of a stable genome. To understand these fundamental processes, we have chosen to use yeast as a model system that allows genetics, molecular biology and advanced live microscopy approaches to be combined. Budding yeast have been very powerful to demonstrate that gene position can play an active role in regulating gene expression. Distinct subcompartments dedicated to either gene silencing or activation of specific genes are positioned at the nuclear periphery. To gain insight into the mechanisms underlying this sub-compartmentalization, we will address three complementary issues: - What are the mechanisms involved in the establishment and maintenance of silent nuclear compartments? - How and why are some activated genes recruited to the nuclear periphery? - What are the relationships between repressive and activating nuclear compartments? Concerning the maintenance of genome integrity, recent advances in yeast highlight the importance of nuclear architecture. However, how nuclear organization influences the formation and processing of DNA lesions remain poorly understood. We will focus on two main questions: - How and where in the nucleus are double strand breaks recognized, processed, and repaired? - Where do breaks or gaps resulting from replicative stress at 'fragile sites' arise in the nucleus and how does nuclear organization influence their stability? We hope to gain a better understanding of the mechanisms presiding nuclear organization and its importance for genome functions. These mechanisms are likely to be conserved and will be subsequently tested in higher eukaryotic cells.
Max ERC Funding
1 000 000 €
Duration
Start date: 2008-09-01, End date: 2014-05-31
