Project acronym ACE-OF-SPACE
Project Analysis, control, and engineering of spatiotemporal pattern formation
Researcher (PI) Patrick MueLLER
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Country Germany
Call Details Consolidator Grant (CoG), LS3, ERC-2019-COG
Summary A central problem in developmental biology is to understand how tissues are patterned in time and space - how do identical cells differentiate to form the adult body plan? Patterns often arise from prior asymmetries in developing embryos, but there is also increasing evidence for self-organizing mechanisms that can break the symmetry of an initially homogeneous cell population. These patterning processes are mediated by a small number of signaling molecules, including the TGF-β superfamily members BMP and Nodal. While we have begun to analyze how biophysical properties such as signal diffusion and stability contribute to axis formation and tissue allocation during vertebrate embryogenesis, three key questions remain. First, how does signaling cross-talk control robust patterning in developing tissues? Opposing sources of Nodal and BMP are sufficient to produce secondary zebrafish axes, but it is unclear how the signals interact to orchestrate this mysterious process. Second, how do signaling systems self-organize to pattern tissues in the absence of prior asymmetries? Recent evidence indicates that axis formation in mammalian embryos is independent of maternal and extra-embryonic tissues, but the mechanism underlying this self-organized patterning is unknown. Third, what are the minimal requirements to engineer synthetic self-organizing systems? Our theoretical analyses suggest that self-organizing reaction-diffusion systems are more common and robust than previously thought, but this has so far not been experimentally demonstrated. We will address these questions in zebrafish embryos, mouse embryonic stem cells, and bacterial colonies using a combination of quantitative imaging, optogenetics, mathematical modeling, and synthetic biology. In addition to providing insights into signaling and development, this high-risk/high-gain approach opens exciting new strategies for tissue engineering by providing asymmetric or temporally regulated signaling in organ precursors.
Summary
A central problem in developmental biology is to understand how tissues are patterned in time and space - how do identical cells differentiate to form the adult body plan? Patterns often arise from prior asymmetries in developing embryos, but there is also increasing evidence for self-organizing mechanisms that can break the symmetry of an initially homogeneous cell population. These patterning processes are mediated by a small number of signaling molecules, including the TGF-β superfamily members BMP and Nodal. While we have begun to analyze how biophysical properties such as signal diffusion and stability contribute to axis formation and tissue allocation during vertebrate embryogenesis, three key questions remain. First, how does signaling cross-talk control robust patterning in developing tissues? Opposing sources of Nodal and BMP are sufficient to produce secondary zebrafish axes, but it is unclear how the signals interact to orchestrate this mysterious process. Second, how do signaling systems self-organize to pattern tissues in the absence of prior asymmetries? Recent evidence indicates that axis formation in mammalian embryos is independent of maternal and extra-embryonic tissues, but the mechanism underlying this self-organized patterning is unknown. Third, what are the minimal requirements to engineer synthetic self-organizing systems? Our theoretical analyses suggest that self-organizing reaction-diffusion systems are more common and robust than previously thought, but this has so far not been experimentally demonstrated. We will address these questions in zebrafish embryos, mouse embryonic stem cells, and bacterial colonies using a combination of quantitative imaging, optogenetics, mathematical modeling, and synthetic biology. In addition to providing insights into signaling and development, this high-risk/high-gain approach opens exciting new strategies for tissue engineering by providing asymmetric or temporally regulated signaling in organ precursors.
Max ERC Funding
1 997 750 €
Duration
Start date: 2020-07-01, End date: 2025-06-30
Project acronym ACHIEVE
Project Advanced Cellular Hierarchical Tissue-Imitations based on Excluded Volume Effect
Researcher (PI) Dimitrios ZEVGOLIS
Host Institution (HI) NATIONAL UNIVERSITY OF IRELAND GALWAY
Country Ireland
Call Details Consolidator Grant (CoG), PE8, ERC-2019-COG
Summary ACHIEVE focuses on the application of Excluded Volume Effect in cell culture systems in order to enhance Extracellular Matrix (ECM) deposition. It represents a new horizon in in vitro cell culture which will address major challenges in medical advancement and food security. ACHIEVE will elucidate extracellular processes which occur during tissue generation, identifying favourable conditions for optimum tissue cultivation in vitro. These results will be applied in the diverse fields of regenerative medicine, drug discovery and cellular agriculture which all require advancements in in vitro tissue engineering to overcome current bottlenecks. Effective in vitro tissue culture is currently limited by lengthy culture periods. An inability to maintain physiologic (in vivo) conditions during this lengthy in vitro culture leads to cellular phenotype drift, ultimately resulting in generation of an undesired tissue. Enhanced tissue generation in vitro will greatly reduce culture times and costs, effecting improved in vitro tissue substitutes which remain true to their original phenotype. The research will be addressed under four work-packages. WP1 will investigate biochemical, biophysical and biological responses to varying culture conditions; WP 2, 3 and 4 will apply results in the fields of Tissue Engineering, Drug Discovery and Cellular Agriculture respectively. Research will involve extensive characterisation of derived- and stem-cell cultures in varying conditions of expansion and relevant health and safety and preclinical testing. The five year programme will be undertaken at the National University of Ireland, Galway, a centre of excellence in tissue engineering research, at a cost of € 2,439,270.
Summary
ACHIEVE focuses on the application of Excluded Volume Effect in cell culture systems in order to enhance Extracellular Matrix (ECM) deposition. It represents a new horizon in in vitro cell culture which will address major challenges in medical advancement and food security. ACHIEVE will elucidate extracellular processes which occur during tissue generation, identifying favourable conditions for optimum tissue cultivation in vitro. These results will be applied in the diverse fields of regenerative medicine, drug discovery and cellular agriculture which all require advancements in in vitro tissue engineering to overcome current bottlenecks. Effective in vitro tissue culture is currently limited by lengthy culture periods. An inability to maintain physiologic (in vivo) conditions during this lengthy in vitro culture leads to cellular phenotype drift, ultimately resulting in generation of an undesired tissue. Enhanced tissue generation in vitro will greatly reduce culture times and costs, effecting improved in vitro tissue substitutes which remain true to their original phenotype. The research will be addressed under four work-packages. WP1 will investigate biochemical, biophysical and biological responses to varying culture conditions; WP 2, 3 and 4 will apply results in the fields of Tissue Engineering, Drug Discovery and Cellular Agriculture respectively. Research will involve extensive characterisation of derived- and stem-cell cultures in varying conditions of expansion and relevant health and safety and preclinical testing. The five year programme will be undertaken at the National University of Ireland, Galway, a centre of excellence in tissue engineering research, at a cost of € 2,439,270.
Max ERC Funding
2 076 770 €
Duration
Start date: 2020-09-01, End date: 2025-08-31
Project acronym ACQUIRE
Project Assessing cardiac Contractility and Quantification of Underlying mechanisms In vitro via Response in Excitation-contraction coupling
Researcher (PI) Christine MUMMERY
Host Institution (HI) ACADEMISCH ZIEKENHUIS LEIDEN
Country Netherlands
Call Details Proof of Concept (PoC), ERC-2019-PoC
Summary "Academia and industry urgently needs reliable models to study heart failure and toxic effects of drugs on the heart. While new models based on human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are now emerging, accurate readouts of cardiomyocyte function fall short of needs. Apart from improving the models biologically, more sensitive, informative and accurate readouts are needed to detect abnormal cardiomyocyte behaviour. Several tools have proven their ability to assess electrical changes or calcium handling in hiPSC-CMs, but they are typically incompatible with 3D tissue models and moreover, there is paucity of appropriate tools to quantify the most important function of myocardium: contraction. Our ERC Advanced Grant STEMCARDIOVASC entailed the development of improved tools for cardiac functionality. One of the most important bioassays developed as an outcome of STEMCARDIOVASC was the Triple Transient Measurement (TTM) System. The TTM System quantifies electrical activity, intracellular calcium flux and contractility simultaneously and is our answer to the challenge of pharma in understanding when and how drugs or diseases affect cardiac contractility using hiPSC-CM models. In this ERC Proof of Concept project “ACQUIRE”, we strive to bring the TTM to a commercial applicable service, and later product. To reach this goal we have set out four aims to come to a Minimum Viable Product: i) increase the flexibility of the system to accommodate a larger variety of optical probes, ii) increase the throughput of the system to compete with current measurement systems, iii) increase user friendliness by integrating software modules for running and analysing measurements and iv) define a route for commercialisation.
Resulting from ""ACQUIRE"" the TTM System can be commercialized as a human cardiac based 3-in-1 assay for cardiotoxicity testing and a novel tool for providing mechanistic insight in the EC coupling for disease modelling and drug discovery."
Summary
"Academia and industry urgently needs reliable models to study heart failure and toxic effects of drugs on the heart. While new models based on human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are now emerging, accurate readouts of cardiomyocyte function fall short of needs. Apart from improving the models biologically, more sensitive, informative and accurate readouts are needed to detect abnormal cardiomyocyte behaviour. Several tools have proven their ability to assess electrical changes or calcium handling in hiPSC-CMs, but they are typically incompatible with 3D tissue models and moreover, there is paucity of appropriate tools to quantify the most important function of myocardium: contraction. Our ERC Advanced Grant STEMCARDIOVASC entailed the development of improved tools for cardiac functionality. One of the most important bioassays developed as an outcome of STEMCARDIOVASC was the Triple Transient Measurement (TTM) System. The TTM System quantifies electrical activity, intracellular calcium flux and contractility simultaneously and is our answer to the challenge of pharma in understanding when and how drugs or diseases affect cardiac contractility using hiPSC-CM models. In this ERC Proof of Concept project “ACQUIRE”, we strive to bring the TTM to a commercial applicable service, and later product. To reach this goal we have set out four aims to come to a Minimum Viable Product: i) increase the flexibility of the system to accommodate a larger variety of optical probes, ii) increase the throughput of the system to compete with current measurement systems, iii) increase user friendliness by integrating software modules for running and analysing measurements and iv) define a route for commercialisation.
Resulting from ""ACQUIRE"" the TTM System can be commercialized as a human cardiac based 3-in-1 assay for cardiotoxicity testing and a novel tool for providing mechanistic insight in the EC coupling for disease modelling and drug discovery."
Max ERC Funding
150 000 €
Duration
Start date: 2020-09-01, End date: 2022-02-28
Project acronym ActiDrops
Project Synthetic Active Droplets Inspired by Life
Researcher (PI) Job BOEKHOVEN
Host Institution (HI) TECHNISCHE UNIVERSITAET MUENCHEN
Country Germany
Call Details Starting Grant (StG), PE5, ERC-2019-STG
Summary Active droplets are made of molecular building blocks that are activated and deactivated by a chemical reaction cycle. In the activation, a precursor is converted into a building block for droplets driven by the consumption of fuel. In the deactivation, the building blocks react back to the precursor. In other words, active droplets emerge when fuel is supplied, but decay when fuel is depleted. Theoretical studies show active droplets all evolve to the same size. Another work predicts that the droplets can spontaneously self-divide when energy is abundant. All of these exciting properties, i.e., emergence, decay, collective behavior, and self-division are pivotal to the functioning of life. If we could engineer these behaviors in synthetic materials, we would obtain a better understanding of active assembly which is directly relevant to biology and the origin of life.
I thus aim to synthesize active droplets and study their life-like properties. Two types of active droplets will be investigated; one type based on oil-molecules that phase separate in water, and one type based on cationic peptides in a complex coacervate with RNA. My team will develop reaction cycles that drive the droplet formation, thereby making them active. We will study their spontaneous emergence in response to energy, and disappearance when energy is scarce. Moreover, we study their collective behavior, like how they grow into one large droplet, or all converge to the same droplet volume. Finally, we test their division into daughter droplets. Our systematic approach will test how kinetic parameters, like the activation rate, affect the behavior of the droplets.
The results will mark a massive step forward in the engineering of materials with life-like behaviors, which can also serve as experimental models for membrane-less organelles. We expect to elucidate mechanisms that could have played a role in the origin of life. Finally, our findings could form stepping stones towards a synthetic cel.
Summary
Active droplets are made of molecular building blocks that are activated and deactivated by a chemical reaction cycle. In the activation, a precursor is converted into a building block for droplets driven by the consumption of fuel. In the deactivation, the building blocks react back to the precursor. In other words, active droplets emerge when fuel is supplied, but decay when fuel is depleted. Theoretical studies show active droplets all evolve to the same size. Another work predicts that the droplets can spontaneously self-divide when energy is abundant. All of these exciting properties, i.e., emergence, decay, collective behavior, and self-division are pivotal to the functioning of life. If we could engineer these behaviors in synthetic materials, we would obtain a better understanding of active assembly which is directly relevant to biology and the origin of life.
I thus aim to synthesize active droplets and study their life-like properties. Two types of active droplets will be investigated; one type based on oil-molecules that phase separate in water, and one type based on cationic peptides in a complex coacervate with RNA. My team will develop reaction cycles that drive the droplet formation, thereby making them active. We will study their spontaneous emergence in response to energy, and disappearance when energy is scarce. Moreover, we study their collective behavior, like how they grow into one large droplet, or all converge to the same droplet volume. Finally, we test their division into daughter droplets. Our systematic approach will test how kinetic parameters, like the activation rate, affect the behavior of the droplets.
The results will mark a massive step forward in the engineering of materials with life-like behaviors, which can also serve as experimental models for membrane-less organelles. We expect to elucidate mechanisms that could have played a role in the origin of life. Finally, our findings could form stepping stones towards a synthetic cel.
Max ERC Funding
1 491 350 €
Duration
Start date: 2020-02-01, End date: 2025-01-31
Project acronym ACTIVATE
Project Augmenting the Value of Conversations with Voice Transformations
Researcher (PI) Jean-Julien AUCOUTURIER
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Proof of Concept (PoC), ERC-2019-PoC
Summary Project ACTIVATE aims to bring to market real-time voice-transformation technologies based on ERC CREAM's research in emotion neuroscience, which can augment the value of spoken conversations by adding business-relevant control on emotional expressivity. For instance, in the context of a call-center conversation, our real-time voice transformations may make an angry client’s voice 10% less aggressive, reducing employee fatigue at the end of the day, or make an operator’s voice 10% more trustworthy, augmenting customer satisfaction after the call. Project ACTIVATE will (1) conduct market analyses and interviews of industrial players to identify relevant conversational situations in which the technologies can be tested (e.g. for a call-center, a customer calling to resiliate their contract), (2) identify precise conversation outcomes that have market value (e.g. retention rate after the call), (3) measure the impact of the voice transformation on these outcomes in a simulated test environment that is near the desired configuration in terms of performance and user performance and (4) use the technology’s measured impact on relevant variables (e.g. a X% increase of retention rate) to estimate the value of a minimally-viable product (MVP), to be taken to market by a startup company to be created at the end of the project.
Summary
Project ACTIVATE aims to bring to market real-time voice-transformation technologies based on ERC CREAM's research in emotion neuroscience, which can augment the value of spoken conversations by adding business-relevant control on emotional expressivity. For instance, in the context of a call-center conversation, our real-time voice transformations may make an angry client’s voice 10% less aggressive, reducing employee fatigue at the end of the day, or make an operator’s voice 10% more trustworthy, augmenting customer satisfaction after the call. Project ACTIVATE will (1) conduct market analyses and interviews of industrial players to identify relevant conversational situations in which the technologies can be tested (e.g. for a call-center, a customer calling to resiliate their contract), (2) identify precise conversation outcomes that have market value (e.g. retention rate after the call), (3) measure the impact of the voice transformation on these outcomes in a simulated test environment that is near the desired configuration in terms of performance and user performance and (4) use the technology’s measured impact on relevant variables (e.g. a X% increase of retention rate) to estimate the value of a minimally-viable product (MVP), to be taken to market by a startup company to be created at the end of the project.
Max ERC Funding
150 000 €
Duration
Start date: 2020-09-01, End date: 2022-02-28
Project acronym AD_AGING_AND_GENDER
Project Unmasking cellular and molecular networks encoding risk and resilience in Alzheimer’s disease
Researcher (PI) Naomi Miriam Habib
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Country Israel
Call Details Starting Grant (StG), LS5, ERC-2019-STG
Summary AlzheimerAlzheimer’s disease (AD) is a crucial problem in our society, raising the need for new therapeutic targets. Evidence suggests multiple non-neuronal cells are implicated in the systemic deficits of AD, but the complex cellular diversity in the brain hampers the investigation of specific cells and their interactions. Moreover, the course of the disease is highly variable, due to multiple risk factors, including aging and gender, which have overlapping molecular signatures with AD that might be further masking disease mechanisms.
I propose to expand the resolution from tissues to cellular environments, and to untangle overlapping molecular signatures of gender and aging, in order to unmask molecular mechanism of AD. Technological advances in genomics and imaging, including the single nucleus RNA-sequencing methods developed by me, as well as my expertise in computational analysis and CRIPSR perturbations, provide a unique opportunity to address this challenge. I obtained preliminary results strongly suggesting that multiple cell types are indeed altered in AD brains of mice and humans, and that gender, aging, and AD have overlapping molecular features. I hypothesize that age-dependent cellular/molecular alterations are key drivers of cognitive decline, and that the dynamics of these alterations determine risk and resilience levels in individuals.
We will test this hypothesis by: 1) Charting the cellular microenvironments and tissue topology of the human AD brain, to reveal cells, pathways, and cellular interactions driving AD; 2) Mapping the dynamic cellular/molecular trajectories in aging and AD in w.t. and AD mice, to untangle AD, aging, and gender dimorphism; and 3) Identifying regulators of cognitive resilience and decline in AD and aging, and connecting genes to function by detailed mechanistic investigations in vivo.
Overall, our innovative proposal is expected to advance our understanding of AD mechanism, and the link to aging and gender dimorphism.
Summary
AlzheimerAlzheimer’s disease (AD) is a crucial problem in our society, raising the need for new therapeutic targets. Evidence suggests multiple non-neuronal cells are implicated in the systemic deficits of AD, but the complex cellular diversity in the brain hampers the investigation of specific cells and their interactions. Moreover, the course of the disease is highly variable, due to multiple risk factors, including aging and gender, which have overlapping molecular signatures with AD that might be further masking disease mechanisms.
I propose to expand the resolution from tissues to cellular environments, and to untangle overlapping molecular signatures of gender and aging, in order to unmask molecular mechanism of AD. Technological advances in genomics and imaging, including the single nucleus RNA-sequencing methods developed by me, as well as my expertise in computational analysis and CRIPSR perturbations, provide a unique opportunity to address this challenge. I obtained preliminary results strongly suggesting that multiple cell types are indeed altered in AD brains of mice and humans, and that gender, aging, and AD have overlapping molecular features. I hypothesize that age-dependent cellular/molecular alterations are key drivers of cognitive decline, and that the dynamics of these alterations determine risk and resilience levels in individuals.
We will test this hypothesis by: 1) Charting the cellular microenvironments and tissue topology of the human AD brain, to reveal cells, pathways, and cellular interactions driving AD; 2) Mapping the dynamic cellular/molecular trajectories in aging and AD in w.t. and AD mice, to untangle AD, aging, and gender dimorphism; and 3) Identifying regulators of cognitive resilience and decline in AD and aging, and connecting genes to function by detailed mechanistic investigations in vivo.
Overall, our innovative proposal is expected to advance our understanding of AD mechanism, and the link to aging and gender dimorphism.
Max ERC Funding
1 500 000 €
Duration
Start date: 2020-06-01, End date: 2025-05-31
Project acronym ADAM
Project Autonomous Discovery of Advanced Materials
Researcher (PI) Graeme DAY, Andrew Cooper, Kerstin Thurow
Host Institution (HI) UNIVERSITY OF SOUTHAMPTON
Country United Kingdom
Call Details Synergy Grants (SyG), SyG, ERC-2019-SyG
Summary Materials impact most aspects of our lives, including healthcare, energy production, data storage and pollution control. However, the design of functional materials cannot be approached with the certainty and the engineering rules that would be used in planning and constructing a macroscopic object, such as a car or bridge. This is because of the limited scope for design that exists at the atomic scale: experimentally realizable materials must correspond to local minima on a complex, multidimensional energy surface, whose positions and depths are difficult to predict. This project will change the way that we discover new molecular materials by revolutionizing the exploration process, rather than focussing on rules for intuitive design. This will be achieved through a unique synergistic partnership between three principal investigators, bringing together an international leader in crystal structure modelling and prediction methods, an experimental chemist with a track record for inventing new classes of functional materials, and a pioneer in robotics for laboratory and process automation. The programme integrates state-of-the-art computation, experiment and robotics, building on joint breakthroughs from our team (Nature, 2011; Nature, 2017) that lay the groundwork for a transformation in our materials discovery capabilities. We will build a Computational Engine for evolutionary exploration of chemical space using crystal structure prediction and machine learning of structure-property relationships for the assessment of molecules. In parallel, we will develop an Experimental Engine for autonomous synthesis and properties testing using newly-developed, artificially-intelligent, mobile ‘robot chemists’. The vision of ADAM is to couple these two engines together, creating an autonomous discovery platform that amplifies human creativity by searching the vast, unexplored chemical space for new materials with step change properties.
Summary
Materials impact most aspects of our lives, including healthcare, energy production, data storage and pollution control. However, the design of functional materials cannot be approached with the certainty and the engineering rules that would be used in planning and constructing a macroscopic object, such as a car or bridge. This is because of the limited scope for design that exists at the atomic scale: experimentally realizable materials must correspond to local minima on a complex, multidimensional energy surface, whose positions and depths are difficult to predict. This project will change the way that we discover new molecular materials by revolutionizing the exploration process, rather than focussing on rules for intuitive design. This will be achieved through a unique synergistic partnership between three principal investigators, bringing together an international leader in crystal structure modelling and prediction methods, an experimental chemist with a track record for inventing new classes of functional materials, and a pioneer in robotics for laboratory and process automation. The programme integrates state-of-the-art computation, experiment and robotics, building on joint breakthroughs from our team (Nature, 2011; Nature, 2017) that lay the groundwork for a transformation in our materials discovery capabilities. We will build a Computational Engine for evolutionary exploration of chemical space using crystal structure prediction and machine learning of structure-property relationships for the assessment of molecules. In parallel, we will develop an Experimental Engine for autonomous synthesis and properties testing using newly-developed, artificially-intelligent, mobile ‘robot chemists’. The vision of ADAM is to couple these two engines together, creating an autonomous discovery platform that amplifies human creativity by searching the vast, unexplored chemical space for new materials with step change properties.
Max ERC Funding
9 999 283 €
Duration
Start date: 2020-10-01, End date: 2026-09-30
Project acronym ADAMtx
Project ADAMtx: Development of Alzheimer’s immunotherapy by harnessing the natural reparative properties of microglia
Researcher (PI) Ido AMIT
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Country Israel
Call Details Proof of Concept (PoC), ERC-2019-PoC
Summary Alzheimer's disease (AD) is a heterogeneous disease in which multiple detrimental factors contribute to cognitive loss and disease escalation. Currently there are no effective therapies for AD. Targeting any single symptom of disease-escalating factor (e.g. amyloid beta, tau, neuroinflammation etc.), even if successful, is not sufficient to modify the disease, as seen in the multiple failures of recent phase-III clinical trials. Thus, there is a desperate need for new approaches for development of AD therapeutics, which will be more comprehensive and not etiology-specific. Using single cell genomic analysis of the immune system in AD mouse models, we discovered a novel microglia type, disease associated microglia (DAM), intrinsic immune cells of the brain that fight AD and neurodegenerative disease. There are several revolutionary aspects to our approach to modify AD course. Fundamentally, based on our unique DAM pathways and target discovery platform we will develop novel AD-immunotherapy for boosting the brain’s innate neuroprotective mechanisms that fight neurodegeneration in AD. Development of targets that boost DAM cells is a major activity of this PoC plan, and we are in different phases of development of several targets that increase DAM activity including advanced stages of the targets Trem2 and P2ry12. The first goal of this PoC grant is to develop and strengthen our IP around AD immunotherapy targets. The second goal is to design a viable and scalable business model with venture capital and establish a startup (ADAMtheraputics) that will translate our novel technology for effective AD-immunotherapy for Alzheimer patients. We believe that our unique approach of targeting the brain’s intrinsic protective immune cells, to boost their activity and numbers, will dramatically impact AD therapy.
Summary
Alzheimer's disease (AD) is a heterogeneous disease in which multiple detrimental factors contribute to cognitive loss and disease escalation. Currently there are no effective therapies for AD. Targeting any single symptom of disease-escalating factor (e.g. amyloid beta, tau, neuroinflammation etc.), even if successful, is not sufficient to modify the disease, as seen in the multiple failures of recent phase-III clinical trials. Thus, there is a desperate need for new approaches for development of AD therapeutics, which will be more comprehensive and not etiology-specific. Using single cell genomic analysis of the immune system in AD mouse models, we discovered a novel microglia type, disease associated microglia (DAM), intrinsic immune cells of the brain that fight AD and neurodegenerative disease. There are several revolutionary aspects to our approach to modify AD course. Fundamentally, based on our unique DAM pathways and target discovery platform we will develop novel AD-immunotherapy for boosting the brain’s innate neuroprotective mechanisms that fight neurodegeneration in AD. Development of targets that boost DAM cells is a major activity of this PoC plan, and we are in different phases of development of several targets that increase DAM activity including advanced stages of the targets Trem2 and P2ry12. The first goal of this PoC grant is to develop and strengthen our IP around AD immunotherapy targets. The second goal is to design a viable and scalable business model with venture capital and establish a startup (ADAMtheraputics) that will translate our novel technology for effective AD-immunotherapy for Alzheimer patients. We believe that our unique approach of targeting the brain’s intrinsic protective immune cells, to boost their activity and numbers, will dramatically impact AD therapy.
Max ERC Funding
150 000 €
Duration
Start date: 2019-10-01, End date: 2021-03-31
Project acronym ADDITIVES
Project Exposure to ‘cocktails’ of food additives and chronic disease risk
Researcher (PI) Mathilde Touvier
Host Institution (HI) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Country France
Call Details Consolidator Grant (CoG), LS7, ERC-2019-COG
Summary Today, our daily diet typically contains dozens of food additives (e.g. colours, emulsifiers, sweeteners: ~350 substances allowed on the EU market). Safety assessment is performed by health agencies to protect consumers against potential adverse effects of each additive, yet such an assessment is only based on current available evidence, i.e., for most additives, only in-vitro/in-vivo toxicological studies and exposure simulations. Meanwhile, the long-term health impact of additives intake and any potential ‘cocktail’ effects remain largely unknown and have become a source of serious concern. Growing evidence link the consumption of ultra-processed foods, containing numerous additives, to adverse health outcomes, in particular our recent results on cancer (Fiolet BMJ 2018). While most additives allowed in the EU are likely to be neutral for health and some may even be beneficial, recent animal and cell-based studies have suggested detrimental effects of several such compounds. In humans, data is lacking. No epidemiological study has ever assessed individual-level exposure to a wide range of food additives and its association with health, hampered by unsuited traditional dietary assessment tools facing the high additive content variability across commercial brands. Hence, a major breakthrough will come from the novel and unique tools I developed with my team, notably within the NutriNet-Santé cohort (n=164,000), collecting precise and repeated data on foods and beverages usually consumed, including names and brands of industrial products. With this unique resource, I propose a project at the forefront of international research to provide answers to a question of major importance for public health. Built as a combination of epidemiological studies and in-vitro/in-vivo experiments, this project will shed light on individual exposure to food additive 'cocktails' in relation to obesity, cancer, cardiovascular diseases and mortality, while depicting underlying mechanisms.
Summary
Today, our daily diet typically contains dozens of food additives (e.g. colours, emulsifiers, sweeteners: ~350 substances allowed on the EU market). Safety assessment is performed by health agencies to protect consumers against potential adverse effects of each additive, yet such an assessment is only based on current available evidence, i.e., for most additives, only in-vitro/in-vivo toxicological studies and exposure simulations. Meanwhile, the long-term health impact of additives intake and any potential ‘cocktail’ effects remain largely unknown and have become a source of serious concern. Growing evidence link the consumption of ultra-processed foods, containing numerous additives, to adverse health outcomes, in particular our recent results on cancer (Fiolet BMJ 2018). While most additives allowed in the EU are likely to be neutral for health and some may even be beneficial, recent animal and cell-based studies have suggested detrimental effects of several such compounds. In humans, data is lacking. No epidemiological study has ever assessed individual-level exposure to a wide range of food additives and its association with health, hampered by unsuited traditional dietary assessment tools facing the high additive content variability across commercial brands. Hence, a major breakthrough will come from the novel and unique tools I developed with my team, notably within the NutriNet-Santé cohort (n=164,000), collecting precise and repeated data on foods and beverages usually consumed, including names and brands of industrial products. With this unique resource, I propose a project at the forefront of international research to provide answers to a question of major importance for public health. Built as a combination of epidemiological studies and in-vitro/in-vivo experiments, this project will shed light on individual exposure to food additive 'cocktails' in relation to obesity, cancer, cardiovascular diseases and mortality, while depicting underlying mechanisms.
Max ERC Funding
2 000 000 €
Duration
Start date: 2020-05-01, End date: 2025-04-30
Project acronym AdjustNet
Project Self-Adjusting Networks
Researcher (PI) Stefan SCHMID
Host Institution (HI) UNIVERSITAT WIEN
Country Austria
Call Details Consolidator Grant (CoG), PE6, ERC-2019-COG
Summary Communication networks have become a critical infrastructure of our digital society. However, with the explosive growth of data-centric applications and the resulting increasing workloads headed for the world’s datacenter networks, today’s static and demand-oblivious network architectures are reaching their capacity limits.
The AdjustNet project proposes a radically different perspective, envisioning demand-aware networks which can dynamically adapt their topology to the workload they currently serve. Such self-adjusting networks hence allow to exploit structure in the demand, and thereby reach higher levels of efficiency and performance. The vision of AdjustNet is timely and enabled by recent innovations in optical technologies which allow to flexibly reconfigure the physical network topology.
The goal of AdjustNet is to lay the theoretical foundations for self-adjusting networks. We will identify metrics that serve as yardstick of what can and cannot be achieved in a self-adjusting network for a given demand, devise algorithms for online adaption, and validate our framework through case studies. Our novel methodology is motivated by an intriguing connection of self-adjusting networks to known datastructures and to information theory.
AdjustNet comes with significant challenges since, similar to self-driving cars, self-adjusting networks require human network operators to give away control, and since more autonomous network operations may lead to instabilities. AdjustNet will overcome these risks and achieve its objectives by pursuing a rigorous approach, devising a theoretical well-founded framework for self-adjusting networks which come with provable guarantees and incorporate self–protection mechanisms.
The PI is well-equipped for this project and recently obtained first promising results. As the community is currently re-architecting communication networks, there is a unique opportunity to bridge the gap between theory and practice, and have impact.
Summary
Communication networks have become a critical infrastructure of our digital society. However, with the explosive growth of data-centric applications and the resulting increasing workloads headed for the world’s datacenter networks, today’s static and demand-oblivious network architectures are reaching their capacity limits.
The AdjustNet project proposes a radically different perspective, envisioning demand-aware networks which can dynamically adapt their topology to the workload they currently serve. Such self-adjusting networks hence allow to exploit structure in the demand, and thereby reach higher levels of efficiency and performance. The vision of AdjustNet is timely and enabled by recent innovations in optical technologies which allow to flexibly reconfigure the physical network topology.
The goal of AdjustNet is to lay the theoretical foundations for self-adjusting networks. We will identify metrics that serve as yardstick of what can and cannot be achieved in a self-adjusting network for a given demand, devise algorithms for online adaption, and validate our framework through case studies. Our novel methodology is motivated by an intriguing connection of self-adjusting networks to known datastructures and to information theory.
AdjustNet comes with significant challenges since, similar to self-driving cars, self-adjusting networks require human network operators to give away control, and since more autonomous network operations may lead to instabilities. AdjustNet will overcome these risks and achieve its objectives by pursuing a rigorous approach, devising a theoretical well-founded framework for self-adjusting networks which come with provable guarantees and incorporate self–protection mechanisms.
The PI is well-equipped for this project and recently obtained first promising results. As the community is currently re-architecting communication networks, there is a unique opportunity to bridge the gap between theory and practice, and have impact.
Max ERC Funding
1 670 823 €
Duration
Start date: 2020-03-01, End date: 2025-02-28
