Project acronym 2D4D
Project Disruptive Digitalization for Decarbonization
Researcher (PI) Elena Verdolini
Host Institution (HI) UNIVERSITA DEGLI STUDI DI BRESCIA
Country Italy
Call Details Starting Grant (StG), SH2, ERC-2019-STG
Summary By 2040, all major sectors of the European economy will be deeply digitalized. By then, the EU aims at reducing greenhouse gas emissions by 60% with respect to 1990 levels. Digitalization will affect decarbonization efforts because of its impacts on energy demand, employment, competitiveness, trade patterns and its distributional, behavioural and ethical implications. Yet, the policy debates around these two transformations are largely disjoint.
The aim of the 2D4D project is ensure that the digital revolution acts as an enabler – and not as a barrier – for decarbonization. The project quantifies the decarbonization implications of three disruptive digitalization technologies in hard-to-decarbonize sectors: (1) Additive Manufacturing in industry, (2) Mobility-as-a-Service in transportation, and (3) Artificial Intelligence in buildings.
The first objective of 2D4D is to generate a one-of-a-kind data collection to investigate the technical and socio-economic dynamics of these technologies, and how they may affect decarbonization narratives and scenarios. This will be achieved through several data collection methods, including desk research, surveys and expert elicitations.
The second objective of 2D4D is to include digitalization dynamics in decarbonization narratives and pathways. On the one hand, this entails enhancing decarbonization narratives (specifically, the Shared Socio-economic Pathways) to describe digitalization dynamics. On the other hand, it requires improving the representation of sector-specific digitalization dynamics in Integrated Assessment Models, one of the main tools available to generate decarbonization pathways.
The third objective of 2D4D is to identify no-regret, robust policy portfolios. These will be designed to ensure that digitalization unfolds in an inclusive, climate-beneficial way, and that decarbonization policies capitalize on digital technologies to support the energy transition.
Summary
By 2040, all major sectors of the European economy will be deeply digitalized. By then, the EU aims at reducing greenhouse gas emissions by 60% with respect to 1990 levels. Digitalization will affect decarbonization efforts because of its impacts on energy demand, employment, competitiveness, trade patterns and its distributional, behavioural and ethical implications. Yet, the policy debates around these two transformations are largely disjoint.
The aim of the 2D4D project is ensure that the digital revolution acts as an enabler – and not as a barrier – for decarbonization. The project quantifies the decarbonization implications of three disruptive digitalization technologies in hard-to-decarbonize sectors: (1) Additive Manufacturing in industry, (2) Mobility-as-a-Service in transportation, and (3) Artificial Intelligence in buildings.
The first objective of 2D4D is to generate a one-of-a-kind data collection to investigate the technical and socio-economic dynamics of these technologies, and how they may affect decarbonization narratives and scenarios. This will be achieved through several data collection methods, including desk research, surveys and expert elicitations.
The second objective of 2D4D is to include digitalization dynamics in decarbonization narratives and pathways. On the one hand, this entails enhancing decarbonization narratives (specifically, the Shared Socio-economic Pathways) to describe digitalization dynamics. On the other hand, it requires improving the representation of sector-specific digitalization dynamics in Integrated Assessment Models, one of the main tools available to generate decarbonization pathways.
The third objective of 2D4D is to identify no-regret, robust policy portfolios. These will be designed to ensure that digitalization unfolds in an inclusive, climate-beneficial way, and that decarbonization policies capitalize on digital technologies to support the energy transition.
Max ERC Funding
1 498 375 €
Duration
Start date: 2020-10-01, End date: 2025-09-30
Project acronym 3D-In-Macro
Project Inequality in 3D – measurement and implications for macroeconomic theory
Researcher (PI) Andreas Fagereng
Host Institution (HI) STIFTELSEN HANDELSHOYSKOLEN BI
Country Norway
Call Details Starting Grant (StG), SH1, ERC-2019-STG
Summary This project will contribute toward a better understanding of inequality and its macroeconomic implications. We will study inequality and its dynamics along three dimensions: Consumption, Income and Wealth, “3D Inequality.” With novel microdata we can measure the entirety of the economy down to the single household along the 3 dimensions.
In macroeconomics, much theoretical progress has been made in understanding when distributions matter for aggregates. Newer heterogeneous agent models deliver strikingly different implications for monetary and fiscal policies than what the traditional representative agent models do, and also allow us to study the distributional implications of different policies across households. In principle, this class of models can incorporate the potentially rich interactions between inequality and the macroeconomy: on the one hand, inequality shapes macroeconomic aggregates; on the other hand, macroeconomic shocks and policies affect inequality. However, absent precise micro-level facts it is difficult to establish which of the potential mechanisms highlighted by these models are the most important in reality.
Our empirical efforts will be disciplined by these recent developments in modelling macroeconomic phenomena with microeconomic heterogeneity. Our overarching motivation is to quantify the type of micro heterogeneity that matters for macroeconomic theory and thereby inform the development of current and future macroeconomic models. The novel insights we aim to provide could lead to substantial improvements in both fiscal and monetary policy tools. Furthermore, a better understanding of the forces behind growing inequality will inform the current debate on this issue and provide important lessons to policy makers who see economic inequality as a problem in itself.
Summary
This project will contribute toward a better understanding of inequality and its macroeconomic implications. We will study inequality and its dynamics along three dimensions: Consumption, Income and Wealth, “3D Inequality.” With novel microdata we can measure the entirety of the economy down to the single household along the 3 dimensions.
In macroeconomics, much theoretical progress has been made in understanding when distributions matter for aggregates. Newer heterogeneous agent models deliver strikingly different implications for monetary and fiscal policies than what the traditional representative agent models do, and also allow us to study the distributional implications of different policies across households. In principle, this class of models can incorporate the potentially rich interactions between inequality and the macroeconomy: on the one hand, inequality shapes macroeconomic aggregates; on the other hand, macroeconomic shocks and policies affect inequality. However, absent precise micro-level facts it is difficult to establish which of the potential mechanisms highlighted by these models are the most important in reality.
Our empirical efforts will be disciplined by these recent developments in modelling macroeconomic phenomena with microeconomic heterogeneity. Our overarching motivation is to quantify the type of micro heterogeneity that matters for macroeconomic theory and thereby inform the development of current and future macroeconomic models. The novel insights we aim to provide could lead to substantial improvements in both fiscal and monetary policy tools. Furthermore, a better understanding of the forces behind growing inequality will inform the current debate on this issue and provide important lessons to policy makers who see economic inequality as a problem in itself.
Max ERC Funding
1 376 875 €
Duration
Start date: 2020-05-01, End date: 2025-04-30
Project acronym 3D-loop
Project Mechanism of homology search and the logic of homologous chromosome pairing in meiosis
Researcher (PI) Aurele PIAZZA
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Starting Grant (StG), LS2, ERC-2019-STG
Summary Homologous recombination (HR) is a conserved DNA double-strand breaks (DSB) repair pathway that uniquely uses an intact DNA molecule as a template. Genome-wide homology search is carried out by a nucleoprotein filament (NPF) assembled on the ssDNA flanking the DSB, and whose product is a “D-loop” joint molecule. Beyond accurate DSB repair, this capacity of HR to spatially associates homologous molecules is also harnessed for homolog pairing in meiosis. The goal of “3D-loop” is to tackle two long lasting conundrums: the fundamental homology search mechanism that achieves accurate and efficient identification of a single homologous donor in the vastness of the genome and nucleus, and how this mechanism is adapted for the purpose of homologs attachment in meiosis.
I overcame the main hurdle to study these core steps of HR by developing a suite of proximity ligation-based methodologies and experimental systems to physically detect joint molecules in yeast cells. It revealed elaborate regulation controlling D-loop dynamics and a novel class of joint molecules. This proposal builds upon these methodologies and findings to first address basic properties of the homology sampling process by the NPF and the role of D-loop dynamics, with the long-term goal to establish a quantitative framework of homology search in mitotic cells (WP1). Second, the meiosis-specific regulation of homology search leading to homolog pairing likely integrates chromosomal-scale information. Genome re-synthesis and engineering approaches will be deployed to (i) achieve a quantitative and dynamic cartography of the cytological and molecular events of meiosis over a large chromosomal region, (ii) probe cis-acting regulations at the chromosomal scale, and (iii) revisit the molecular paradigm for crossover formation (WP2). We expect this project to shed light on the fundamental process of homology search and its involvement in the chromosome pairing phenomenon lying at the basis of sexual reproduction.
Summary
Homologous recombination (HR) is a conserved DNA double-strand breaks (DSB) repair pathway that uniquely uses an intact DNA molecule as a template. Genome-wide homology search is carried out by a nucleoprotein filament (NPF) assembled on the ssDNA flanking the DSB, and whose product is a “D-loop” joint molecule. Beyond accurate DSB repair, this capacity of HR to spatially associates homologous molecules is also harnessed for homolog pairing in meiosis. The goal of “3D-loop” is to tackle two long lasting conundrums: the fundamental homology search mechanism that achieves accurate and efficient identification of a single homologous donor in the vastness of the genome and nucleus, and how this mechanism is adapted for the purpose of homologs attachment in meiosis.
I overcame the main hurdle to study these core steps of HR by developing a suite of proximity ligation-based methodologies and experimental systems to physically detect joint molecules in yeast cells. It revealed elaborate regulation controlling D-loop dynamics and a novel class of joint molecules. This proposal builds upon these methodologies and findings to first address basic properties of the homology sampling process by the NPF and the role of D-loop dynamics, with the long-term goal to establish a quantitative framework of homology search in mitotic cells (WP1). Second, the meiosis-specific regulation of homology search leading to homolog pairing likely integrates chromosomal-scale information. Genome re-synthesis and engineering approaches will be deployed to (i) achieve a quantitative and dynamic cartography of the cytological and molecular events of meiosis over a large chromosomal region, (ii) probe cis-acting regulations at the chromosomal scale, and (iii) revisit the molecular paradigm for crossover formation (WP2). We expect this project to shed light on the fundamental process of homology search and its involvement in the chromosome pairing phenomenon lying at the basis of sexual reproduction.
Max ERC Funding
1 499 779 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym 3DPartForm
Project 3D-printing of PARTiculate FORMulations utilizing polymer microparticle-based voxels
Researcher (PI) Julian Thiele
Host Institution (HI) LEIBNIZ-INSTITUT FUR POLYMERFORSCHUNG DRESDEN EV
Country Germany
Call Details Starting Grant (StG), PE8, ERC-2019-STG
Summary New polymer materials are necessary to match the demand for highly integrated, multifunctional, responsive systems for sensing, information processing, soft robotics or multi-parametric implants. Both established
material design concepts based on lithography, and emerging engineering efforts based on additive manufacturing (AM) are currently not able to fully address the need for topologically complex, multifunctional
and stimuli-responsive polymer materials. This proposal aims at establishing a radically new approach for polymer material design, rethinking AM on both material and process level. Here, functionality will be already
embedded at the building block level to emerge into larger scales. The exact methodology relies on polymer microparticles as a novel material basis with arbitrary geometry, function, mechanics and responsiveness.
These microparticulate formulations will serve as predefined, voxel-like building blocks in AM yielding hierarchical assemblies with spatially defined voxel position and programmable, adaptive properties, which clearly go beyond existing functional material classes. With that, 3DPartForm will address the current lack of additive manufacturing providing multifunctional, stimuli-responsive materials, in which not only strongly different, but most importantly functional building blocks with intrinsic time axis will be processed into true 4D-polymer multimaterials. Products emerging from this approach will reach a previously unknown level of system integration, where optical transparency, electric and thermal conductivity as well as diffusivity and mechanical rigidity will become spatiotemporally tunable at single-voxel level. Coupled sensing and actuation operations will be realized by processing, transforming and manipulating single or combined input stimuli within these materials in the focus of 3DPartform, and platforms for biomimetics and cell-free biotechnology will be implemented as a long-term goal.
Summary
New polymer materials are necessary to match the demand for highly integrated, multifunctional, responsive systems for sensing, information processing, soft robotics or multi-parametric implants. Both established
material design concepts based on lithography, and emerging engineering efforts based on additive manufacturing (AM) are currently not able to fully address the need for topologically complex, multifunctional
and stimuli-responsive polymer materials. This proposal aims at establishing a radically new approach for polymer material design, rethinking AM on both material and process level. Here, functionality will be already
embedded at the building block level to emerge into larger scales. The exact methodology relies on polymer microparticles as a novel material basis with arbitrary geometry, function, mechanics and responsiveness.
These microparticulate formulations will serve as predefined, voxel-like building blocks in AM yielding hierarchical assemblies with spatially defined voxel position and programmable, adaptive properties, which clearly go beyond existing functional material classes. With that, 3DPartForm will address the current lack of additive manufacturing providing multifunctional, stimuli-responsive materials, in which not only strongly different, but most importantly functional building blocks with intrinsic time axis will be processed into true 4D-polymer multimaterials. Products emerging from this approach will reach a previously unknown level of system integration, where optical transparency, electric and thermal conductivity as well as diffusivity and mechanical rigidity will become spatiotemporally tunable at single-voxel level. Coupled sensing and actuation operations will be realized by processing, transforming and manipulating single or combined input stimuli within these materials in the focus of 3DPartform, and platforms for biomimetics and cell-free biotechnology will be implemented as a long-term goal.
Max ERC Funding
1 474 125 €
Duration
Start date: 2020-04-01, End date: 2025-03-31
Project acronym 3DPBio
Project Computational Models of Motion for Fabrication-aware Design of Bioinspired Systems
Researcher (PI) Stelian Coros
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Consolidator Grant (CoG), PE6, ERC-2019-COG
Summary "Bridging the fields of Computer Animation and Computational Fabrication, this proposal will establish the foundations for algorithmic design of physical structures that can generate lifelike movements. Driven by embedded actuators, these types of structures will enable an abundance of possibilities for a wide array of real-world technologies: animatronic characters whose organic motions will enhance their ability to awe, entertain and educate; soft robotic creatures that are both skilled and safe to be around; patient-specific prosthetics and wearable devices that match the soft touch of the human body, etc. Recent advances in additive manufacturing (AM) technologies are particularly exciting in this context, as they allow us to create designs of unparalleled geometric complexity using a constantly expanding range of materials. And if past developments are an indication, within the next decade we will be able to fabricate physical structures that approach, at least at the macro scale, the functional sophistication of their biological counterparts. However, while this unprecedented capability enables fascinating opportunities, it also leads to an explosion in the dimensionality of the space that must be explored during the design process. As AM technologies keep evolving, the gap between ""what we can produce"" and ""what we can design"" is therefore rapidly growing.
To effectively leverage the extraordinary design possibilities enabled by AM, 3DPBio will develop the computational and mathematical foundations required to study a fundamental scientific question: how are physical deformations, mechanical movements and overall functional capabilities governed by geometric shape features, material compositions and the design of compliant actuation systems? By enabling computers to reason about this question, our work will establish new ways to algorithmically create digital designs that can be turned into mechanical lifeforms at the push of a button."
Summary
"Bridging the fields of Computer Animation and Computational Fabrication, this proposal will establish the foundations for algorithmic design of physical structures that can generate lifelike movements. Driven by embedded actuators, these types of structures will enable an abundance of possibilities for a wide array of real-world technologies: animatronic characters whose organic motions will enhance their ability to awe, entertain and educate; soft robotic creatures that are both skilled and safe to be around; patient-specific prosthetics and wearable devices that match the soft touch of the human body, etc. Recent advances in additive manufacturing (AM) technologies are particularly exciting in this context, as they allow us to create designs of unparalleled geometric complexity using a constantly expanding range of materials. And if past developments are an indication, within the next decade we will be able to fabricate physical structures that approach, at least at the macro scale, the functional sophistication of their biological counterparts. However, while this unprecedented capability enables fascinating opportunities, it also leads to an explosion in the dimensionality of the space that must be explored during the design process. As AM technologies keep evolving, the gap between ""what we can produce"" and ""what we can design"" is therefore rapidly growing.
To effectively leverage the extraordinary design possibilities enabled by AM, 3DPBio will develop the computational and mathematical foundations required to study a fundamental scientific question: how are physical deformations, mechanical movements and overall functional capabilities governed by geometric shape features, material compositions and the design of compliant actuation systems? By enabling computers to reason about this question, our work will establish new ways to algorithmically create digital designs that can be turned into mechanical lifeforms at the push of a button."
Max ERC Funding
2 000 000 €
Duration
Start date: 2020-02-01, End date: 2025-01-31
Project acronym 3DScavengers
Project Three-dimensional nanoscale design for the all-in-one solution to environmental multisource energy scavenging
Researcher (PI) Ana Isabel BORRAS MARTOS
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Country Spain
Call Details Starting Grant (StG), PE8, ERC-2019-STG
Summary Imagine a technology for powering your smart devices by recovering energy from lights in your office, the random movements of your body while reading these lines or from small changes in temperature when you breathe or go out for a walk. This very technology will provide energy for wireless sensor networks monitoring the air in your city or the structural stability of buildings and large constructions remotely and sustainably, avoiding battery recharging or even replacing them. These are the challenges in micro energy harvesting from (local) ambient sources.
Kinetic, thermal and solar energies are ubiquitous at our surroundings under diverse forms, but their relatively low intensity and intermittent availability limit their potential recovery by microscale devices. These restrictions call for multi-source energy harvesters working under two principles: 1) combining different single-source harvesters in one device, or 2) using multifunctional materials capable of simultaneously converting various energy sources into electricity. In 1), efficiency per unit volume can decrease compared to the individual counterparts; in 2), materials as semiconductors, polymeric and oxide ferroelectrics and hybrid perovskites may act as multisource harvesters but huge advances are required to optimize their functionalities and sustainable fabrication at large scale.
I propose to fill the gap between these approaches offering an all-in-one solution to multisource energy scavenging, based on the nanoscale design of multifunctional three-dimensional materials. The demonstration of an industrially scalable one-reactor plasma/vacuum method will be crucial to integrate hybrid-scavenging components and to provide 3DScavengers materials with tailored microstructure-enhanced performance.
My ultimate goal is to build nanoarchitectures for simultaneous and enhanced individual scavenging applying photovoltaic, piezo- and pyro-electric effects, minimizing the environmental cost of their synthesis
Summary
Imagine a technology for powering your smart devices by recovering energy from lights in your office, the random movements of your body while reading these lines or from small changes in temperature when you breathe or go out for a walk. This very technology will provide energy for wireless sensor networks monitoring the air in your city or the structural stability of buildings and large constructions remotely and sustainably, avoiding battery recharging or even replacing them. These are the challenges in micro energy harvesting from (local) ambient sources.
Kinetic, thermal and solar energies are ubiquitous at our surroundings under diverse forms, but their relatively low intensity and intermittent availability limit their potential recovery by microscale devices. These restrictions call for multi-source energy harvesters working under two principles: 1) combining different single-source harvesters in one device, or 2) using multifunctional materials capable of simultaneously converting various energy sources into electricity. In 1), efficiency per unit volume can decrease compared to the individual counterparts; in 2), materials as semiconductors, polymeric and oxide ferroelectrics and hybrid perovskites may act as multisource harvesters but huge advances are required to optimize their functionalities and sustainable fabrication at large scale.
I propose to fill the gap between these approaches offering an all-in-one solution to multisource energy scavenging, based on the nanoscale design of multifunctional three-dimensional materials. The demonstration of an industrially scalable one-reactor plasma/vacuum method will be crucial to integrate hybrid-scavenging components and to provide 3DScavengers materials with tailored microstructure-enhanced performance.
My ultimate goal is to build nanoarchitectures for simultaneous and enhanced individual scavenging applying photovoltaic, piezo- and pyro-electric effects, minimizing the environmental cost of their synthesis
Max ERC Funding
1 498 414 €
Duration
Start date: 2020-03-01, End date: 2025-02-28
Project acronym AccelOnChip
Project Attosecond physics, free electron quantum optics, photon generation and radiation biology with the accelerator on a photonic chip
Researcher (PI) Peter HOMMELHOFF
Host Institution (HI) FRIEDRICH-ALEXANDER-UNIVERSITAET ERLANGEN-NUERNBERG
Country Germany
Call Details Advanced Grant (AdG), PE2, ERC-2019-ADG
Summary Resting on our demonstration of laser-driven nanophotonics-based particle acceleration, we propose to build a miniature particle accelerator on a photonic chip, comprising high gradient acceleration and fully optical field-based electron control. The resulting electron beam has outstanding space-time properties: It is bunched on sub-femtosecond timescales, is nanometres wide and coherent. We aim at utilizing this new form of all-optical free electron control in a broad research program with five exciting objectives:
(1) Build a 5 MeV accelerator on a photonic chip in a shoebox-sized vessel,
(2) Perform ultrafast diffraction with attosecond and even zeptosecond electron pulses,
(3) Generate photons on chip at various wavelengths (IR to x-ray),
(4) Couple quantum-coherently electron wavepackets and light in multiple interaction zones, and
(5) Conduct radiobiological experiments, akin to the new FLASH radiotherapy and Microbeam cell treat-ment.
AccelOnChip will enable five science objectives potentially shifting the horizons of today’s knowledge and capabilities around ultrafast electron imaging, photon generation, (quantum) electron-light coupling, and radiotherapy dramatically. Moreover, AccelOnChip promises to democratize accelerators: the accelerator on a chip will be based on inexpensive nanofabrication technology. We foresee that every university lab can have access to particle and light sources, today only accessible at large facilities. Last, AccelOnChip will take decisive steps towards an ultracompact electron beam radiation device to be put into the tip of a catheter, a potentially disruptive radiation therapy device facilitating new treatment forms. AccelOnChip is a cross-disciplinary high risk/high return project combining and benefiting nanophotonics, accelerator science, ultra-fast physics, materials science, coherent light-matter coupling, light generation, and radiology - and is based on my group’s unique expertise acquired in recent years.
Summary
Resting on our demonstration of laser-driven nanophotonics-based particle acceleration, we propose to build a miniature particle accelerator on a photonic chip, comprising high gradient acceleration and fully optical field-based electron control. The resulting electron beam has outstanding space-time properties: It is bunched on sub-femtosecond timescales, is nanometres wide and coherent. We aim at utilizing this new form of all-optical free electron control in a broad research program with five exciting objectives:
(1) Build a 5 MeV accelerator on a photonic chip in a shoebox-sized vessel,
(2) Perform ultrafast diffraction with attosecond and even zeptosecond electron pulses,
(3) Generate photons on chip at various wavelengths (IR to x-ray),
(4) Couple quantum-coherently electron wavepackets and light in multiple interaction zones, and
(5) Conduct radiobiological experiments, akin to the new FLASH radiotherapy and Microbeam cell treat-ment.
AccelOnChip will enable five science objectives potentially shifting the horizons of today’s knowledge and capabilities around ultrafast electron imaging, photon generation, (quantum) electron-light coupling, and radiotherapy dramatically. Moreover, AccelOnChip promises to democratize accelerators: the accelerator on a chip will be based on inexpensive nanofabrication technology. We foresee that every university lab can have access to particle and light sources, today only accessible at large facilities. Last, AccelOnChip will take decisive steps towards an ultracompact electron beam radiation device to be put into the tip of a catheter, a potentially disruptive radiation therapy device facilitating new treatment forms. AccelOnChip is a cross-disciplinary high risk/high return project combining and benefiting nanophotonics, accelerator science, ultra-fast physics, materials science, coherent light-matter coupling, light generation, and radiology - and is based on my group’s unique expertise acquired in recent years.
Max ERC Funding
2 498 508 €
Duration
Start date: 2020-10-01, End date: 2025-09-30
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 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
