Project acronym BARRAGE
Project Cell compartmentalization, individuation and diversity
Researcher (PI) Yves Barral
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), LS3, ERC-2009-AdG
Summary Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.
Summary
Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.
Max ERC Funding
2 200 000 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym BIOCARB
Project Carbonate Biomineralization in the Marine Environment: Paleo-climate proxies and the origin of vital effects
Researcher (PI) Anders Meibom
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Advanced Grant (AdG), PE10, ERC-2009-AdG
Summary This interdisciplinary proposal has the objective to greatly enhance our understanding of fundamental biomineralization processes involved in the formation of calcium carbonates by marine organisms, such as corals, foraminifera and bivalves, in order to better understand vital effects. This is essential to the application of these carbonates as proxies for global (paleo-) environmental change. The core of the proposal is an experimental capability that I have pioneered during 2008: Dynamic stable isotopic labeling during formation of carbonate skeletons, tests, and shells, combined with NanoSIMS imaging. The NanoSIMS ion microprobe is a state-of-the-art analytical technology that allows precise elemental and isotopic imaging with a spatial resolution of ~100 nanometers. NanoSIMS imaging of the isotopic label(s) in the resulting biocarbonates and in associated cell-structures will be used to uncover cellular-level transport processes, timescales of formation of different biocarbonate components, as well as trace-elemental and isotopic fractionations. This will uncover the origin of vital effects. With this proposal, I establish a new scientific frontier and guarantee European leadership. The technical and scientific developments resulting from this work are broadly applicable and will radically change scientific ideas about marine carbonate biomineralization and compositional vital effects.
Summary
This interdisciplinary proposal has the objective to greatly enhance our understanding of fundamental biomineralization processes involved in the formation of calcium carbonates by marine organisms, such as corals, foraminifera and bivalves, in order to better understand vital effects. This is essential to the application of these carbonates as proxies for global (paleo-) environmental change. The core of the proposal is an experimental capability that I have pioneered during 2008: Dynamic stable isotopic labeling during formation of carbonate skeletons, tests, and shells, combined with NanoSIMS imaging. The NanoSIMS ion microprobe is a state-of-the-art analytical technology that allows precise elemental and isotopic imaging with a spatial resolution of ~100 nanometers. NanoSIMS imaging of the isotopic label(s) in the resulting biocarbonates and in associated cell-structures will be used to uncover cellular-level transport processes, timescales of formation of different biocarbonate components, as well as trace-elemental and isotopic fractionations. This will uncover the origin of vital effects. With this proposal, I establish a new scientific frontier and guarantee European leadership. The technical and scientific developments resulting from this work are broadly applicable and will radically change scientific ideas about marine carbonate biomineralization and compositional vital effects.
Max ERC Funding
2 182 000 €
Duration
Start date: 2010-07-01, End date: 2015-06-30
Project acronym BIOGEOS
Project Bio-mediated Geo-material Strengthening for engineering applications
Researcher (PI) Lyesse LALOUI
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Advanced Grant (AdG), PE8, ERC-2017-ADG
Summary Given the increasing scarcity of suitable land for development, soil strengthening technologies have emerged in the past decade and go hand-in-hand with the implementation of the majority of foundation solutions. The goal is to alter the soil structure and its mechanical properties for ultimately securing the integrity of structures. The BIOGEOS project puts the focus on bio-mediated soil improvement, which falls within the broader framework of multi-physical processes in geo-mechanics. The goal of the project is to engineer a novel, natural material under controlled processes, for ultimately providing solutions to real problems in the geo-engineering and geo-energy fields by advancing knowledge around complex multi-physical phenomena in porous media. The bio-cemented geo-material, which is produced by carefully integrating the metabolic activity of native soil bacteria, is produced through the bio-mineralization of calcite bonds, which act as natural cementation for endowing the subsurface with real cohesion and increased resistance. A principal characteristic of the project is its multi-scale approach through advanced experimentation to identify the main physical mechanisms involved in the formation of the bio-mineralized bonds and their behaviour under mechanical loading. The development of such a bio-mediated technology will lead to innovative applications in a series of engineering problems such as the restoration of weak foundations, seismic retrofitting, erosion protection, and the enhancement of heat transfer in thermo-active geo-structures. The project foresees to adopt multiple loading conditions for its laboratory characterization and ultimately pass to the large experimental scale. BIOGEOS further aims to provide new knowledge around the way we perceive materials in relation with their micro-structure by implementing state-of-the-art inspection of the material’s structure in 3D space and subsequent prediction of their behaviour through numerical tools.
Summary
Given the increasing scarcity of suitable land for development, soil strengthening technologies have emerged in the past decade and go hand-in-hand with the implementation of the majority of foundation solutions. The goal is to alter the soil structure and its mechanical properties for ultimately securing the integrity of structures. The BIOGEOS project puts the focus on bio-mediated soil improvement, which falls within the broader framework of multi-physical processes in geo-mechanics. The goal of the project is to engineer a novel, natural material under controlled processes, for ultimately providing solutions to real problems in the geo-engineering and geo-energy fields by advancing knowledge around complex multi-physical phenomena in porous media. The bio-cemented geo-material, which is produced by carefully integrating the metabolic activity of native soil bacteria, is produced through the bio-mineralization of calcite bonds, which act as natural cementation for endowing the subsurface with real cohesion and increased resistance. A principal characteristic of the project is its multi-scale approach through advanced experimentation to identify the main physical mechanisms involved in the formation of the bio-mineralized bonds and their behaviour under mechanical loading. The development of such a bio-mediated technology will lead to innovative applications in a series of engineering problems such as the restoration of weak foundations, seismic retrofitting, erosion protection, and the enhancement of heat transfer in thermo-active geo-structures. The project foresees to adopt multiple loading conditions for its laboratory characterization and ultimately pass to the large experimental scale. BIOGEOS further aims to provide new knowledge around the way we perceive materials in relation with their micro-structure by implementing state-of-the-art inspection of the material’s structure in 3D space and subsequent prediction of their behaviour through numerical tools.
Max ERC Funding
2 497 115 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym BIOMOL. SIMULATION
Project Development of multi-scale molecular models, force fields and computer software for biomolecular simulation
Researcher (PI) Willem Frederik Van Gunsteren
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE4, ERC-2008-AdG
Summary During the past decades the PI has helped shape the research field of computer simulation of biomolecular systems at the atomic level. He has carried out one of the first molecular dynamics (MD) simulations of proteins, and has since then contributed many different methodological improvements and developed one of the major atomic-level force fields for simulations of proteins, carbohydrates, nucleotides and lipids. Methodology and force field have been implemented in a set of programs called GROMOS (GROningen MOlecular Simulation package), which is currently used in hundreds of academic and industrial research groups from over 50 countries on all continents. It is proposed to develop a next generation of molecular models, force fields, multi-scaling simulation methodology and software for biomolecular simulations which is at least an order of magnitude more accurate in terms of energetics, and which is 1000 times more efficient through the use of coarse-grained molecular models than the currently available software and models.
Summary
During the past decades the PI has helped shape the research field of computer simulation of biomolecular systems at the atomic level. He has carried out one of the first molecular dynamics (MD) simulations of proteins, and has since then contributed many different methodological improvements and developed one of the major atomic-level force fields for simulations of proteins, carbohydrates, nucleotides and lipids. Methodology and force field have been implemented in a set of programs called GROMOS (GROningen MOlecular Simulation package), which is currently used in hundreds of academic and industrial research groups from over 50 countries on all continents. It is proposed to develop a next generation of molecular models, force fields, multi-scaling simulation methodology and software for biomolecular simulations which is at least an order of magnitude more accurate in terms of energetics, and which is 1000 times more efficient through the use of coarse-grained molecular models than the currently available software and models.
Max ERC Funding
1 320 000 €
Duration
Start date: 2008-11-01, End date: 2014-09-30
Project acronym BOTMED
Project Microrobotics and Nanomedicine
Researcher (PI) Bradley James Nelson
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE7, ERC-2010-AdG_20100224
Summary The introduction of minimally invasive surgery in the 1980’s created a paradigm shift in surgical procedures. Health care is now in a position to make a more dramatic leap by integrating newly developed wireless microrobotic technologies with nanomedicine to perform precisely targeted, localized endoluminal techniques. Devices capable of entering the human body through natural orifices or small incisions to deliver drugs, perform diagnostic procedures, and excise and repair tissue will be used. These new procedures will result in less trauma to the patient and faster recovery times, and will enable new therapies that have not yet been conceived. In order to realize this, many new technologies must be developed and synergistically integrated, and medical therapies for which the technology will prove successful must be aggressively pursued.
This proposed project will result in the realization of animal trials in which wireless microrobotic devices will be used to investigate a variety of extremely delicate ophthalmic therapies. The therapies to be pursued include the delivery of tissue plasminogen activator (t-PA) to blocked retinal veins, the peeling of epiretinal membranes from the retina, and the development of diagnostic procedures based on mapping oxygen concentration at the vitreous-retina interface. With successful animal trials, a path to human trials and commercialization will follow. Clearly, many systems in the body have the potential to benefit from the endoluminal technologies that this project considers, including the digestive system, the circulatory system, the urinary system, the central nervous system, the respiratory system, the female reproductive system and even the fetus. Microrobotic retinal therapies will greatly illuminate the potential that the integration of microrobotics and nanomedicine holds for society, and greatly accelerate this trend in Europe.
Summary
The introduction of minimally invasive surgery in the 1980’s created a paradigm shift in surgical procedures. Health care is now in a position to make a more dramatic leap by integrating newly developed wireless microrobotic technologies with nanomedicine to perform precisely targeted, localized endoluminal techniques. Devices capable of entering the human body through natural orifices or small incisions to deliver drugs, perform diagnostic procedures, and excise and repair tissue will be used. These new procedures will result in less trauma to the patient and faster recovery times, and will enable new therapies that have not yet been conceived. In order to realize this, many new technologies must be developed and synergistically integrated, and medical therapies for which the technology will prove successful must be aggressively pursued.
This proposed project will result in the realization of animal trials in which wireless microrobotic devices will be used to investigate a variety of extremely delicate ophthalmic therapies. The therapies to be pursued include the delivery of tissue plasminogen activator (t-PA) to blocked retinal veins, the peeling of epiretinal membranes from the retina, and the development of diagnostic procedures based on mapping oxygen concentration at the vitreous-retina interface. With successful animal trials, a path to human trials and commercialization will follow. Clearly, many systems in the body have the potential to benefit from the endoluminal technologies that this project considers, including the digestive system, the circulatory system, the urinary system, the central nervous system, the respiratory system, the female reproductive system and even the fetus. Microrobotic retinal therapies will greatly illuminate the potential that the integration of microrobotics and nanomedicine holds for society, and greatly accelerate this trend in Europe.
Max ERC Funding
2 498 044 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym BRAINCOMPATH
Project Mesoscale Brain Dynamics: Computing with Neuronal Pathways
Researcher (PI) Fritjof Helmchen
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Advanced Grant (AdG), LS5, ERC-2014-ADG
Summary Brain computations rely on proper signal flow through the complex network of connected brain regions. Despite a wealth of anatomical and functional data – from microscopic to macroscopic scale – we still poorly understand the principles of how signal flow is routed through neuronal networks to generate appropriate behavior. Brain dynamics on the 'mesoscopic' scale, the intermediate level where local microcircuits communicate via axonal pathways, has remained a particular blind spot of research as it has been difficult to access under in vivo conditions. Here, I propose to tackle the mesoscopic level of brain dynamics both experimentally and theoretically, adopting a fresh perspective centered on neuronal pathway dynamics. Experimentally, we will utilize and further advance state-of-the-art genetic and optical techniques to create a toolbox for measuring and manipulating signal flow in pathway networks across a broad range of temporal scales. In particular, we will improve fiber-optic based methods for probing the activity of either individual or multiple neuronal pathways with high specificity. Using these tools we will set out to reveal mesoscopic brain dynamics across relevant cortical and subcortical regions in awake, behaving mice. Specifically, we will investigate sensorimotor learning for a reward-based texture discrimination task and rapid sensorimotor control during skilled locomotion. Moreover, by combining fiber-optic methods with two-photon microscopy and fMRI, respectively, we will start linking the meso-level to the micro- and macro-levels. Throughout the project, experiments will be complemented by computational approaches to analyse data, model pathway dynamics, and conceptualize a formal theory of mesoscopic dynamics. This project may transform the field by bridging the hierarchical brain levels and opening significant new avenues to assess physiological as well as pathological signal flow in the brain.
Summary
Brain computations rely on proper signal flow through the complex network of connected brain regions. Despite a wealth of anatomical and functional data – from microscopic to macroscopic scale – we still poorly understand the principles of how signal flow is routed through neuronal networks to generate appropriate behavior. Brain dynamics on the 'mesoscopic' scale, the intermediate level where local microcircuits communicate via axonal pathways, has remained a particular blind spot of research as it has been difficult to access under in vivo conditions. Here, I propose to tackle the mesoscopic level of brain dynamics both experimentally and theoretically, adopting a fresh perspective centered on neuronal pathway dynamics. Experimentally, we will utilize and further advance state-of-the-art genetic and optical techniques to create a toolbox for measuring and manipulating signal flow in pathway networks across a broad range of temporal scales. In particular, we will improve fiber-optic based methods for probing the activity of either individual or multiple neuronal pathways with high specificity. Using these tools we will set out to reveal mesoscopic brain dynamics across relevant cortical and subcortical regions in awake, behaving mice. Specifically, we will investigate sensorimotor learning for a reward-based texture discrimination task and rapid sensorimotor control during skilled locomotion. Moreover, by combining fiber-optic methods with two-photon microscopy and fMRI, respectively, we will start linking the meso-level to the micro- and macro-levels. Throughout the project, experiments will be complemented by computational approaches to analyse data, model pathway dynamics, and conceptualize a formal theory of mesoscopic dynamics. This project may transform the field by bridging the hierarchical brain levels and opening significant new avenues to assess physiological as well as pathological signal flow in the brain.
Max ERC Funding
2 498 915 €
Duration
Start date: 2016-02-01, End date: 2021-01-31
Project acronym BRIDGES
Project Bridging Non-Equilibrium Problems: From the Fourier Law to Gene Expression
Researcher (PI) Jean-Pierre Eckmann
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Advanced Grant (AdG), PE1, ERC-2011-ADG_20110209
Summary My goal is to study several important open mathematical problems in non-equilibrium (NEQ) systems and to build a bridge between these problems and NEQ aspects of soft sciences, in particular biological questions. Traffic on this bridge is going to be two-way, the mathematics carrying a long history as a language of science towards the soft sciences, and the soft sciences fruitfully asking new questions and building new paradigms for mathematical research.
Out-of-equilibrium systems pose several fascinating problems: The Fourier law which says that resistance of a wire is proportional to its length is still presenting hard problems for research, and even the existence and the convergence to a NEQ steady state are continuously posing new puzzles, as do questions of smoothness and correlations of such states. These will be addressed with stochastic differential equations, and with particlescatterer systems, both canonical and grand-canonical. The latter are extensions of the well-known Lorentz gas and the study of hyperbolic billiards.
Another field where NEQ plays an important role is the study of glassy systems. They were studied with molecular dynamics (MD) but I have used a topological variant, which mimics astonishingly well what happens in MD simulations. The aim is to extend this to 3 dimensions, where new problems appear.
Finally, I will apply the NEQ studies to biological systems: How a system copes with the varying environment,adapting in this way to a novel type of NEQ. I will study networks of communication among neurons,which are like random graphs with the additional property of being embedded, and the arrangement of genes on chromosomes in such a way as to optimize the adaptation to the different cell types which must be produced using the same genetic information.
I will answer such questions with students and collaborators, who will specialize in the subprojects but will interact with my help across the common bridge.
Summary
My goal is to study several important open mathematical problems in non-equilibrium (NEQ) systems and to build a bridge between these problems and NEQ aspects of soft sciences, in particular biological questions. Traffic on this bridge is going to be two-way, the mathematics carrying a long history as a language of science towards the soft sciences, and the soft sciences fruitfully asking new questions and building new paradigms for mathematical research.
Out-of-equilibrium systems pose several fascinating problems: The Fourier law which says that resistance of a wire is proportional to its length is still presenting hard problems for research, and even the existence and the convergence to a NEQ steady state are continuously posing new puzzles, as do questions of smoothness and correlations of such states. These will be addressed with stochastic differential equations, and with particlescatterer systems, both canonical and grand-canonical. The latter are extensions of the well-known Lorentz gas and the study of hyperbolic billiards.
Another field where NEQ plays an important role is the study of glassy systems. They were studied with molecular dynamics (MD) but I have used a topological variant, which mimics astonishingly well what happens in MD simulations. The aim is to extend this to 3 dimensions, where new problems appear.
Finally, I will apply the NEQ studies to biological systems: How a system copes with the varying environment,adapting in this way to a novel type of NEQ. I will study networks of communication among neurons,which are like random graphs with the additional property of being embedded, and the arrangement of genes on chromosomes in such a way as to optimize the adaptation to the different cell types which must be produced using the same genetic information.
I will answer such questions with students and collaborators, who will specialize in the subprojects but will interact with my help across the common bridge.
Max ERC Funding
2 135 385 €
Duration
Start date: 2012-04-01, End date: 2017-07-31
Project acronym BROADimmune
Project Structural, genetic and functional analyses of broadly neutralizing antibodies against human pathogens
Researcher (PI) Antonio Lanzavecchia
Host Institution (HI) FONDAZIONE PER L'ISTITUTO DI RICERC A IN BIOMEDICINA
Call Details Advanced Grant (AdG), LS6, ERC-2014-ADG
Summary The overall goal of this project is to understand the molecular mechanisms that lead to the generation of potent and broadly neutralizing antibodies against medically relevant pathogens, and to identify the factors that limit their production in response to infection or vaccination with current vaccines. We will use high-throughput cellular screens to isolate from immune donors clonally related antibodies to different sites of influenza hemagglutinin, which will be fully characterized and sequenced in order to reconstruct their developmental pathways. Using this approach, we will ask fundamental questions with regards to the role of somatic mutations in affinity maturation and intraclonal diversification, which in some cases may lead to the generation of autoantibodies. We will combine crystallography and long time-scale molecular dynamics simulation to understand how mutations can increase affinity and broaden antibody specificity. By mapping the B and T cell response to all sites and conformations of influenza hemagglutinin, we will uncover the factors, such as insufficient T cell help or the instability of the pre-fusion hemagglutinin, that may limit the generation of broadly neutralizing antibodies. We will also perform a broad analysis of the antibody response to erythrocytes infected by P. falciparum to identify conserved epitopes on the parasite and to unravel the role of an enigmatic V gene that appears to be involved in response to blood-stage parasites. The hypotheses tested are strongly supported by preliminary observations from our own laboratory. While these studies will contribute to our understanding of B cell biology, the results obtained will also have translational implications for the development of potent and broad-spectrum antibodies, for the definition of correlates of protection, and for improving vaccine design.
Summary
The overall goal of this project is to understand the molecular mechanisms that lead to the generation of potent and broadly neutralizing antibodies against medically relevant pathogens, and to identify the factors that limit their production in response to infection or vaccination with current vaccines. We will use high-throughput cellular screens to isolate from immune donors clonally related antibodies to different sites of influenza hemagglutinin, which will be fully characterized and sequenced in order to reconstruct their developmental pathways. Using this approach, we will ask fundamental questions with regards to the role of somatic mutations in affinity maturation and intraclonal diversification, which in some cases may lead to the generation of autoantibodies. We will combine crystallography and long time-scale molecular dynamics simulation to understand how mutations can increase affinity and broaden antibody specificity. By mapping the B and T cell response to all sites and conformations of influenza hemagglutinin, we will uncover the factors, such as insufficient T cell help or the instability of the pre-fusion hemagglutinin, that may limit the generation of broadly neutralizing antibodies. We will also perform a broad analysis of the antibody response to erythrocytes infected by P. falciparum to identify conserved epitopes on the parasite and to unravel the role of an enigmatic V gene that appears to be involved in response to blood-stage parasites. The hypotheses tested are strongly supported by preliminary observations from our own laboratory. While these studies will contribute to our understanding of B cell biology, the results obtained will also have translational implications for the development of potent and broad-spectrum antibodies, for the definition of correlates of protection, and for improving vaccine design.
Max ERC Funding
1 867 500 €
Duration
Start date: 2015-10-01, End date: 2020-09-30
Project acronym BSMOXFORD
Project Physics Beyond the Standard Model at the LHC and with Atom Interferometers
Researcher (PI) Savas Dimopoulos
Host Institution (HI) EUROPEAN ORGANIZATION FOR NUCLEAR RESEARCH
Call Details Advanced Grant (AdG), PE2, ERC-2008-AdG
Summary Elementary particle physics is entering a spectacular new era in which experiments at the Large Hadron Collider (LHC) at CERN will soon start probing some of the deepest questions in physics, such as: Why is gravity so weak? Do elementary particles have substructure? What is the origin of mass? Are there new dimensions? Can we produce black holes in the lab? Could there be other universes with different physical laws? While the LHC pushes the energy frontier, the unprecedented precision of Atom Interferometry, has pointed me to a new tool for fundamental physics. These experiments based on the quantum interference of atoms can test General Relativity on the surface of the Earth, detect gravity waves, and test short-distance gravity, charge quantization, and quantum mechanics with unprecedented precision in the next decade. This ERC Advanced grant proposal is aimed at setting up a world-leading European center for development of a deeper theory of fundamental physics. The next 10 years is the optimal time for such studies to benefit from the wealth of new data that will emerge from the LHC, astrophysical observations and atom interferometry. This is a once-in-a-generation opportunity for making ground-breaking progress, and will open up many new research horizons.
Summary
Elementary particle physics is entering a spectacular new era in which experiments at the Large Hadron Collider (LHC) at CERN will soon start probing some of the deepest questions in physics, such as: Why is gravity so weak? Do elementary particles have substructure? What is the origin of mass? Are there new dimensions? Can we produce black holes in the lab? Could there be other universes with different physical laws? While the LHC pushes the energy frontier, the unprecedented precision of Atom Interferometry, has pointed me to a new tool for fundamental physics. These experiments based on the quantum interference of atoms can test General Relativity on the surface of the Earth, detect gravity waves, and test short-distance gravity, charge quantization, and quantum mechanics with unprecedented precision in the next decade. This ERC Advanced grant proposal is aimed at setting up a world-leading European center for development of a deeper theory of fundamental physics. The next 10 years is the optimal time for such studies to benefit from the wealth of new data that will emerge from the LHC, astrophysical observations and atom interferometry. This is a once-in-a-generation opportunity for making ground-breaking progress, and will open up many new research horizons.
Max ERC Funding
2 200 000 €
Duration
Start date: 2009-05-01, End date: 2014-04-30
Project acronym CausalStats
Project Statistics, Prediction and Causality for Large-Scale Data
Researcher (PI) Peter Lukas Bühlmann
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE1, ERC-2017-ADG
Summary Understanding cause-effect relationships between variables is of great interest in many fields of science. However, causal inference from data is much more ambitious and difficult than inferring (undirected) measures of association such as correlations, partial correlations or multivariate regression coefficients, mainly because of fundamental identifiability
problems. A main objective of the proposal is to exploit advantages from large-scale heterogeneous data for causal inference where heterogeneity arises from different experimental conditions or different unknown sub-populations. A key idea is to consider invariance or stability across different experimental conditions of certain conditional probability distributions: the invariants correspond on the one hand to (properly defined) causal variables which are of main interest in causality; andon the other hand, they correspond to the features for constructing powerful predictions for new scenarios which are unobserved in the data (new probability distributions). This opens novel perspectives: causal inference
can be phrased as a prediction problem of a certain kind, and vice versa, new prediction methods which work well across different scenarios (unobserved in the data) should be based on or regularized towards causal variables. Fundamental identifiability limits will become weaker with increased degree of heterogeneity, as we expect in large-scale data. The topic is essentially unexplored, yet it opens new avenues for causal inference, structural equation and graphical modeling, and robust prediction based on large-scale complex data. We will develop mathematical theory, statistical methodology and efficient algorithms; and we will also work and collaborate on major application problems such as inferring causal effects (i.e., total intervention effects) from gene knock-out or RNA interference perturbation experiments, genome-wide association studies and novel prediction tasks in economics.
Summary
Understanding cause-effect relationships between variables is of great interest in many fields of science. However, causal inference from data is much more ambitious and difficult than inferring (undirected) measures of association such as correlations, partial correlations or multivariate regression coefficients, mainly because of fundamental identifiability
problems. A main objective of the proposal is to exploit advantages from large-scale heterogeneous data for causal inference where heterogeneity arises from different experimental conditions or different unknown sub-populations. A key idea is to consider invariance or stability across different experimental conditions of certain conditional probability distributions: the invariants correspond on the one hand to (properly defined) causal variables which are of main interest in causality; andon the other hand, they correspond to the features for constructing powerful predictions for new scenarios which are unobserved in the data (new probability distributions). This opens novel perspectives: causal inference
can be phrased as a prediction problem of a certain kind, and vice versa, new prediction methods which work well across different scenarios (unobserved in the data) should be based on or regularized towards causal variables. Fundamental identifiability limits will become weaker with increased degree of heterogeneity, as we expect in large-scale data. The topic is essentially unexplored, yet it opens new avenues for causal inference, structural equation and graphical modeling, and robust prediction based on large-scale complex data. We will develop mathematical theory, statistical methodology and efficient algorithms; and we will also work and collaborate on major application problems such as inferring causal effects (i.e., total intervention effects) from gene knock-out or RNA interference perturbation experiments, genome-wide association studies and novel prediction tasks in economics.
Max ERC Funding
2 184 375 €
Duration
Start date: 2018-10-01, End date: 2023-09-30