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 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 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 AGEMEC
Project Age-dependent mechanisms of sporadic Alzheimer’s Disease in patient-derived neurons
Researcher (PI) Jerome Stefan MERTENS
Host Institution (HI) UNIVERSITAET INNSBRUCK
Country Austria
Call Details Starting Grant (StG), LS5, ERC-2019-STG
Summary Sporadic Alzheimer’s Disease (AD) accounts for the overwhelming majority of all AD cases and exclusively affects people at old age. However, mechanistic links between aging and AD pathology remain elusive. We recently discovered that in contrast to iPSC models, direct conversion of human fibroblasts into induced neurons (iNs) preserves signatures of aging, and we have started to develop a patient-based iN model system for AD. Our preliminary data suggests that AD iNs show a neuronal but de-differentiated transcriptome signature. In this project, we first combine cellular neuroscience assays and epigenetic landscape profiling to understand how neurons in AD fail to maintain their fully mature differentiated state, which might be key in permitting disease development. Next, using metabolome analysis including mass spec metabolite assessment, we explore a profound metabolic switch in AD iNs that shows surprisingly many aspects of aerobic glycolysis observed also in cancer. While this link might represent an interesting connection between two age-dependent and de-differentiation-associated diseases, it also opens new avenues to harness knowledge from the cancer field to better understand sporadic AD. We further focus on identifying and manipulating key metabolic regulators that appear to malfunction in an age-dependent manner, with the ultimate goal to define potential targets and treatment strategies. Finally, we will focus on early AD mechanisms by extending our model to mild cognitive impairment (MCI) patients. An agnostic transcriptome and epigenetic landscape approach of glutamatergic and serotonergic iNs will help to determine the earliest and probably most treatable disease mechanisms of AD, and to better understand the contribution of neuropsychiatric risk factors. We anticipate that this project will help to illuminate the mechanistic interface of cellular aging and the development of AD, and help to define new strategies for AD.
Summary
Sporadic Alzheimer’s Disease (AD) accounts for the overwhelming majority of all AD cases and exclusively affects people at old age. However, mechanistic links between aging and AD pathology remain elusive. We recently discovered that in contrast to iPSC models, direct conversion of human fibroblasts into induced neurons (iNs) preserves signatures of aging, and we have started to develop a patient-based iN model system for AD. Our preliminary data suggests that AD iNs show a neuronal but de-differentiated transcriptome signature. In this project, we first combine cellular neuroscience assays and epigenetic landscape profiling to understand how neurons in AD fail to maintain their fully mature differentiated state, which might be key in permitting disease development. Next, using metabolome analysis including mass spec metabolite assessment, we explore a profound metabolic switch in AD iNs that shows surprisingly many aspects of aerobic glycolysis observed also in cancer. While this link might represent an interesting connection between two age-dependent and de-differentiation-associated diseases, it also opens new avenues to harness knowledge from the cancer field to better understand sporadic AD. We further focus on identifying and manipulating key metabolic regulators that appear to malfunction in an age-dependent manner, with the ultimate goal to define potential targets and treatment strategies. Finally, we will focus on early AD mechanisms by extending our model to mild cognitive impairment (MCI) patients. An agnostic transcriptome and epigenetic landscape approach of glutamatergic and serotonergic iNs will help to determine the earliest and probably most treatable disease mechanisms of AD, and to better understand the contribution of neuropsychiatric risk factors. We anticipate that this project will help to illuminate the mechanistic interface of cellular aging and the development of AD, and help to define new strategies for AD.
Max ERC Funding
1 499 565 €
Duration
Start date: 2020-02-01, End date: 2025-01-31
Project acronym AGRICON
Project Ancient genomic reconstruction of convergent evolution to agriculture
Researcher (PI) Pontus Rickard Otto Peter Skoglund
Host Institution (HI) THE FRANCIS CRICK INSTITUTE LIMITED
Country United Kingdom
Call Details Starting Grant (StG), LS8, ERC-2019-STG
Summary As global climates warmed ca. 10,000 years ago came a remarkable convergent transformation of human lifestyles that occurred independently in multiple continents and human populations. This transition from hunter-gatherer subsistence to food-production catalysed large-scale population growth, offering the opportunity for increased rates of adaptation, but also rapidly presented a large number of independent human populations with a new evolutionary challenge. This project will use ancient population genomics—the only way to directly reconstruct human genetic evolution—to study whether evolutionary processes during the agricultural transition differed in differed regions. Which genomic adaptations were associated with the agricultural transition? Did adaptation to hunter-gatherer and agricultural lifestyles act on similar genetic architecture in different instances? To which extent did adaptation in domestic dogs—the only species domesticated prior to the agricultural transition—occur in convergence with humans? To answer these questions, the project will generate ancient genomic data from pre-agricultural and early agricultural populations from multiple human- and domestic dog populations from Africa, Central America, and Southeast Asia. This will be achieved with direct sequencing as well as a new human ~850,000 SNP capture panel designed to avoid bias towards Eurasian ancestry. We will also develop new computational methods robust to the challenges posed by ancient genomes to identify adaptive admixture, analyse copy number variation, test continuous population models, and statistically assess convergence in the genomic architecture of adaptation. Leveraging cutting-edge ancient genomics and two model organisms for the genomic basis of phenotypic variation, this project aims to reconstruct the universal evolutionary phenomena underpinning a watershed evolutionary episode that shapes global biodiversity and the human condition to this day.
Summary
As global climates warmed ca. 10,000 years ago came a remarkable convergent transformation of human lifestyles that occurred independently in multiple continents and human populations. This transition from hunter-gatherer subsistence to food-production catalysed large-scale population growth, offering the opportunity for increased rates of adaptation, but also rapidly presented a large number of independent human populations with a new evolutionary challenge. This project will use ancient population genomics—the only way to directly reconstruct human genetic evolution—to study whether evolutionary processes during the agricultural transition differed in differed regions. Which genomic adaptations were associated with the agricultural transition? Did adaptation to hunter-gatherer and agricultural lifestyles act on similar genetic architecture in different instances? To which extent did adaptation in domestic dogs—the only species domesticated prior to the agricultural transition—occur in convergence with humans? To answer these questions, the project will generate ancient genomic data from pre-agricultural and early agricultural populations from multiple human- and domestic dog populations from Africa, Central America, and Southeast Asia. This will be achieved with direct sequencing as well as a new human ~850,000 SNP capture panel designed to avoid bias towards Eurasian ancestry. We will also develop new computational methods robust to the challenges posed by ancient genomes to identify adaptive admixture, analyse copy number variation, test continuous population models, and statistically assess convergence in the genomic architecture of adaptation. Leveraging cutting-edge ancient genomics and two model organisms for the genomic basis of phenotypic variation, this project aims to reconstruct the universal evolutionary phenomena underpinning a watershed evolutionary episode that shapes global biodiversity and the human condition to this day.
Max ERC Funding
1 500 000 €
Duration
Start date: 2019-11-01, End date: 2024-10-31
Project acronym AlgoHex
Project Algorithmic Hexahedral Mesh Generation
Researcher (PI) David Bommes
Host Institution (HI) UNIVERSITAET BERN
Country Switzerland
Call Details Starting Grant (StG), PE6, ERC-2019-STG
Summary "Digital geometry representations are nowadays a fundamental ingredient of many applications, as for instance CAD/CAM, fabrication, shape optimization, bio-medical engineering and numerical simulation. Among volumetric discretizations, the ""holy grail"" are hexahedral meshes, i.e. a decomposition of the domain into conforming cube-like elements. For simulations they offer accuracy and efficiency that cannot be obtained with alternatives like tetrahedral meshes, specifically when dealing with higher-order PDEs. So far, automatic hexahedral meshing of general volumetric domains is a long-standing, notoriously difficult and open problem. Our main goal is to develop algorithms for automatic hexahedral meshing of general volumetric domains that are (i) robust, (ii) scalable and (iii) offer precise control on regularity, approximation error and element sizing/anisotropy. Our approach is designed to replicate the success story of recent integer-grid map based algorithms for 2D quadrilateral meshing. The underlying methodology offers the essential global view on the problem that was lacking in previous attempts. Preliminary results of integer-grid map hexahedral meshing are promising and a breakthrough is in reach. We identified five challenges that need to be addressed in order to reach practically sufficient hexahedral mesh generation. These challenges have partly been resolved in 2D, however, the solutions do not generalize to 3D due to the increased mathematical complexity of 3D manifolds. Nevertheless, with our experience in developing and evaluating the 2D techniques, we identified the key properties that are necessary for success and accordingly propose novel volumetric counterparts that will be developed in the AlgoHex project."
Summary
"Digital geometry representations are nowadays a fundamental ingredient of many applications, as for instance CAD/CAM, fabrication, shape optimization, bio-medical engineering and numerical simulation. Among volumetric discretizations, the ""holy grail"" are hexahedral meshes, i.e. a decomposition of the domain into conforming cube-like elements. For simulations they offer accuracy and efficiency that cannot be obtained with alternatives like tetrahedral meshes, specifically when dealing with higher-order PDEs. So far, automatic hexahedral meshing of general volumetric domains is a long-standing, notoriously difficult and open problem. Our main goal is to develop algorithms for automatic hexahedral meshing of general volumetric domains that are (i) robust, (ii) scalable and (iii) offer precise control on regularity, approximation error and element sizing/anisotropy. Our approach is designed to replicate the success story of recent integer-grid map based algorithms for 2D quadrilateral meshing. The underlying methodology offers the essential global view on the problem that was lacking in previous attempts. Preliminary results of integer-grid map hexahedral meshing are promising and a breakthrough is in reach. We identified five challenges that need to be addressed in order to reach practically sufficient hexahedral mesh generation. These challenges have partly been resolved in 2D, however, the solutions do not generalize to 3D due to the increased mathematical complexity of 3D manifolds. Nevertheless, with our experience in developing and evaluating the 2D techniques, we identified the key properties that are necessary for success and accordingly propose novel volumetric counterparts that will be developed in the AlgoHex project."
Max ERC Funding
1 482 156 €
Duration
Start date: 2020-02-01, End date: 2025-01-31
Project acronym AlgoQIP
Project Beyond Shannon: Algorithms for optimal information processing
Researcher (PI) Omar Fawzi
Host Institution (HI) ECOLE NORMALE SUPERIEURE DE LYON
Country France
Call Details Starting Grant (StG), PE6, ERC-2019-STG
Summary In the road towards quantum technologies capable of exploiting the revolutionary potential of quantum theory for information technology, a major bottleneck is the large overhead needed to correct errors caused by unwanted noise. Despite important research activity and great progress in designing better error correcting codes and fault-tolerant schemes, the fundamental limits of communication/computation over a quantum noisy medium are far from being understood. In fact, no satisfactory quantum analogue of Shannon’s celebrated noisy coding theorem is known.
The objective of this project is to leverage tools from mathematical optimization in order to build an algorithmic theory of optimal information processing that would go beyond the statistical approach pioneered by Shannon. Our goal will be to establish efficient algorithms that determine optimal methods for achieving a given task, rather than only characterizing the best achievable rates in the asymptotic limit in terms of entropic expressions. This approach will address three limitations — that are particularly severe in the quantum context — faced by the statistical approach: the non-additivity of entropic expressions, the asymptotic nature of the theory and the independence assumption.
Our aim is to develop efficient algorithms that take as input a description of a noise model and output a near-optimal method for reliable communication under this model. For example, our algorithms will answer: how many logical qubits can be reliably stored using 100 physical qubits that undergo depolarizing noise with parameter 5%? We will also develop generic and efficient decoding algorithms for quantum error correcting codes. These algorithms will have direct applications to the development of quantum technologies. Moreover, we will establish methods to compute the relevant uncertainty of large structured systems and apply them to obtain tight and non-asymptotic security bounds for (quantum) cryptographic protocols.
Summary
In the road towards quantum technologies capable of exploiting the revolutionary potential of quantum theory for information technology, a major bottleneck is the large overhead needed to correct errors caused by unwanted noise. Despite important research activity and great progress in designing better error correcting codes and fault-tolerant schemes, the fundamental limits of communication/computation over a quantum noisy medium are far from being understood. In fact, no satisfactory quantum analogue of Shannon’s celebrated noisy coding theorem is known.
The objective of this project is to leverage tools from mathematical optimization in order to build an algorithmic theory of optimal information processing that would go beyond the statistical approach pioneered by Shannon. Our goal will be to establish efficient algorithms that determine optimal methods for achieving a given task, rather than only characterizing the best achievable rates in the asymptotic limit in terms of entropic expressions. This approach will address three limitations — that are particularly severe in the quantum context — faced by the statistical approach: the non-additivity of entropic expressions, the asymptotic nature of the theory and the independence assumption.
Our aim is to develop efficient algorithms that take as input a description of a noise model and output a near-optimal method for reliable communication under this model. For example, our algorithms will answer: how many logical qubits can be reliably stored using 100 physical qubits that undergo depolarizing noise with parameter 5%? We will also develop generic and efficient decoding algorithms for quantum error correcting codes. These algorithms will have direct applications to the development of quantum technologies. Moreover, we will establish methods to compute the relevant uncertainty of large structured systems and apply them to obtain tight and non-asymptotic security bounds for (quantum) cryptographic protocols.
Max ERC Funding
1 492 733 €
Duration
Start date: 2021-01-01, End date: 2025-12-31
Project acronym ALPHA
Project Assessing Legacies of Past Human Activities in Amazonia
Researcher (PI) Crystal MCMICHAEL
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Country Netherlands
Call Details Starting Grant (StG), LS8, ERC-2019-STG
Summary Amazon forests contribute vital ecosystem services, including maintaining biodiversity (>10,000 tree species) and storing large amounts of carbon. Amazonia also features prominently in global climate, carbon, and vegetation models, which assume tropical forests are effectively pristine and that past human disturbance mimicked natural processes. It is now evident that recurrent human disturbance of Amazonia, like fire and deforestation, were significant in some areas. Since those disturbances likely modify subsequent vegetation dynamics - including temporarily increasing forest capacity to absorb carbon - the emerging paradigm of human disturbance is a challenge to global ecological understanding. The focus of my project is thus to reliably determine whether human disturbances occurred in locations that form the basis of global models. A key expected outcome is to either legitimize or force revision to these models of carbon sequestration potential in Amazonia.
I will innovatively integrate ecological, paleoecological, archaeological, chemical and biogeographic analyses to assess the degree to which past human disturbance drives the diversity patterns and carbon dynamics observed in modern Amazonian forests. For key long-term sites across Amazonia, I will quantify the: i) time since the last fire, ii) past fire frequency, extent and intensity, iii) past vegetation change in the presence and absence of human activity, and iv) continuity of past human activity over the last 1000 years. My results will provide the first quantification of local-scale recovery processes exceeding 100 years in tropical forests, and will determine if observed forest dynamics are driven by disturbances that occurred before modern ecological surveys began. I will then quantify the extent to which past disturbances create an overestimation of carbon storage potential, driving a profound reexamination of carbon sequestration and biodiversity patterns in Amazonia.
Summary
Amazon forests contribute vital ecosystem services, including maintaining biodiversity (>10,000 tree species) and storing large amounts of carbon. Amazonia also features prominently in global climate, carbon, and vegetation models, which assume tropical forests are effectively pristine and that past human disturbance mimicked natural processes. It is now evident that recurrent human disturbance of Amazonia, like fire and deforestation, were significant in some areas. Since those disturbances likely modify subsequent vegetation dynamics - including temporarily increasing forest capacity to absorb carbon - the emerging paradigm of human disturbance is a challenge to global ecological understanding. The focus of my project is thus to reliably determine whether human disturbances occurred in locations that form the basis of global models. A key expected outcome is to either legitimize or force revision to these models of carbon sequestration potential in Amazonia.
I will innovatively integrate ecological, paleoecological, archaeological, chemical and biogeographic analyses to assess the degree to which past human disturbance drives the diversity patterns and carbon dynamics observed in modern Amazonian forests. For key long-term sites across Amazonia, I will quantify the: i) time since the last fire, ii) past fire frequency, extent and intensity, iii) past vegetation change in the presence and absence of human activity, and iv) continuity of past human activity over the last 1000 years. My results will provide the first quantification of local-scale recovery processes exceeding 100 years in tropical forests, and will determine if observed forest dynamics are driven by disturbances that occurred before modern ecological surveys began. I will then quantify the extent to which past disturbances create an overestimation of carbon storage potential, driving a profound reexamination of carbon sequestration and biodiversity patterns in Amazonia.
Max ERC Funding
1 481 378 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym ANIMATE
Project Adaptive Immunity in Human Atherosclerosis: Understanding its Cellular Basis to Define Novel Immunomodulatory Therapies
Researcher (PI) Dennis Wolf
Host Institution (HI) UNIVERSITAETSKLINIKUM FREIBURG
Country Germany
Call Details Starting Grant (StG), LS4, ERC-2019-STG
Summary Atherosclerosis is a chronic immune disease of arteries that causes vessel-narrowing atherosclerotic plaques. Its acute complications, myocardial infarction and stroke, are the leading causes of death worldwide. Atherosclerosis is accompanied by an inflammatory and autoimmune response with CD4+ T-helper cells that recognize self-antigens, including ApoB-100 (ApoB), the main protein in low-density lipoprotein (LDL) cholesterol. Although their existence has been inferred from indirect evidence, the existence and function of atherosclerosis-specific, self-reactive CD4+ T cells on a single-cell level remains elusive. In particular, it is unclear whether these are pro- or anti-inflammatory.
Preliminary data suggest the existence of a natural pool of ApoB-reactive T-helper cells that share properties with atheroprotective T-regulatory cells but transform into pathogenic T-effector cells in the natural course of disease. This proposal aims to explore this loss of protective immunity on a cellular and function level. It employs novel tools to detect antigen-specific T cells in vivo by MHC-II multimers, mass cytometry (CyTOF), single cell RNA-sequencing (scRNA-seq), lineage-tracing mouse models, and live cell imaging. Based on the anticipated findings, this study will define a map of auto-reactive T-helper cell phenotypes in a temporal, spatial, and functional dimension. These insights will be used to identify novel immunomodulatory strategies to therapeutically stabilize the population of protective ApoB-specific T-helper cells, or to prevent their transformation into pathogenic T cell phenotypes by adoptive cells transfers, vaccination, or cytokine-blockade. In clinical association studies, a direct correlation of auto-immunity and clinical atherosclerosis will be tested.
This proposal will decipher traits of protective immunity in atherosclerosis and help to build the conceptual framework to define novel therapeutic strategies for patients.
Summary
Atherosclerosis is a chronic immune disease of arteries that causes vessel-narrowing atherosclerotic plaques. Its acute complications, myocardial infarction and stroke, are the leading causes of death worldwide. Atherosclerosis is accompanied by an inflammatory and autoimmune response with CD4+ T-helper cells that recognize self-antigens, including ApoB-100 (ApoB), the main protein in low-density lipoprotein (LDL) cholesterol. Although their existence has been inferred from indirect evidence, the existence and function of atherosclerosis-specific, self-reactive CD4+ T cells on a single-cell level remains elusive. In particular, it is unclear whether these are pro- or anti-inflammatory.
Preliminary data suggest the existence of a natural pool of ApoB-reactive T-helper cells that share properties with atheroprotective T-regulatory cells but transform into pathogenic T-effector cells in the natural course of disease. This proposal aims to explore this loss of protective immunity on a cellular and function level. It employs novel tools to detect antigen-specific T cells in vivo by MHC-II multimers, mass cytometry (CyTOF), single cell RNA-sequencing (scRNA-seq), lineage-tracing mouse models, and live cell imaging. Based on the anticipated findings, this study will define a map of auto-reactive T-helper cell phenotypes in a temporal, spatial, and functional dimension. These insights will be used to identify novel immunomodulatory strategies to therapeutically stabilize the population of protective ApoB-specific T-helper cells, or to prevent their transformation into pathogenic T cell phenotypes by adoptive cells transfers, vaccination, or cytokine-blockade. In clinical association studies, a direct correlation of auto-immunity and clinical atherosclerosis will be tested.
This proposal will decipher traits of protective immunity in atherosclerosis and help to build the conceptual framework to define novel therapeutic strategies for patients.
Max ERC Funding
1 499 946 €
Duration
Start date: 2020-01-01, End date: 2024-12-31