Project acronym MCSK
Project "Moduli of curves, sheaves, and K3 surfaces"
Researcher (PI) Rahul Vijay Pandharipande
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE1, ERC-2012-ADG_20120216
Summary "Algebraic geometry is the study of varieties -- the zero sets of polynomial equations in several variables. The subject has a central role in mathematics with connections to number theory, representation theory, and topology. Moduli questions in algebraic geometry concern the behavior of varieties as the coefficients of the defining polynomials vary. At the end of the 20th century several fundamental links between the algebraic geometry of moduli spaces and path integrals in quantum field theory were made. I propose to study the moduli spaces of curves, sheaves, and K3 surfaces. While these moduli problems have independent roots, striking new relationships between them have been found in the past decade. I will exploit the new perspectives to attack central questions concerning the algebra of tautological classes on the moduli spaces of curves, the structure of Gromov-Witten and Donaldson-Thomas invariants of 3-folds including correspondences and Virasoro constraints, the modular properties of the invariants of K3 surfaces, and the Noether-Lefschetz loci of the moduli of K3 surfaces. The proposed approach to these questions uses a mix of new geometries and new techniques. The new geometries include the moduli spaces of stable quotients and stable pairs introduced in the past few years. The new techniques involve a combination of virtual localization, degeneration, and descendent methods together with new ideas from log geometry. The directions discussed here are fundamental to the understanding of moduli spaces in mathematics and their interplay with topology,
string theory, and classical algebraic geometry."
Summary
"Algebraic geometry is the study of varieties -- the zero sets of polynomial equations in several variables. The subject has a central role in mathematics with connections to number theory, representation theory, and topology. Moduli questions in algebraic geometry concern the behavior of varieties as the coefficients of the defining polynomials vary. At the end of the 20th century several fundamental links between the algebraic geometry of moduli spaces and path integrals in quantum field theory were made. I propose to study the moduli spaces of curves, sheaves, and K3 surfaces. While these moduli problems have independent roots, striking new relationships between them have been found in the past decade. I will exploit the new perspectives to attack central questions concerning the algebra of tautological classes on the moduli spaces of curves, the structure of Gromov-Witten and Donaldson-Thomas invariants of 3-folds including correspondences and Virasoro constraints, the modular properties of the invariants of K3 surfaces, and the Noether-Lefschetz loci of the moduli of K3 surfaces. The proposed approach to these questions uses a mix of new geometries and new techniques. The new geometries include the moduli spaces of stable quotients and stable pairs introduced in the past few years. The new techniques involve a combination of virtual localization, degeneration, and descendent methods together with new ideas from log geometry. The directions discussed here are fundamental to the understanding of moduli spaces in mathematics and their interplay with topology,
string theory, and classical algebraic geometry."
Max ERC Funding
2 167 997 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym MEC
Project Macroscopic Entanglement in Crystals
Researcher (PI) Nicolas Robert Gisin
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Advanced Grant (AdG), PE2, ERC-2013-ADG
Summary "Quantum theory is often presented as the theory of the microscopic world. However, over the last decade, things have changed dramatically. Today one can envision manipulating large quantum systems, while mastering individual degrees of freedom. It is thus timely to ask entirely new questions on the quantum/classical transition and to support these by experimental investigations of large entanglement. The vision of this project is to explore conceptually, experimentally and technologically the limits of large entanglement of macroscopically distinguishable quantum states. We propose to demonstrate entanglement between two or more macroscopic crystals with hundreds of entanglement bits (e-bits), hundred of thousands of excitations and billions of ions. For this purpose, we’ll use Neodymium doped YSO crystals and our AFC (Atomic Frequency Comb) protocol for multimode quantum memories.
Since entanglement is the signature of quantumness, this project will demonstrate “macroscopic” entanglement and help sharpening the meaning of “large” and “macroscopic”. By combining theory and experiments, questions like “What is large entanglement?” and “What deserves to be called entanglement between macroscopic systems?” will receive new insightful answers. This will deepen our understanding of Nature and in particular of the intricate meaning of meso- and macroscopic.
Two further goals of this project are to demonstrate large entanglement between two crystals separated by tens of kilometres, and to teleport many qubits stored in a crystal to a distant one.
Although this project is on fundamental questions, it will also contribute to improving the quantum memories required for continental scale ultra-secure quantum communications. We expect other surprising applications, in particular the high sensitivity of large entanglement to various decoherence mechanisms can be turned positively into quantum sensors."
Summary
"Quantum theory is often presented as the theory of the microscopic world. However, over the last decade, things have changed dramatically. Today one can envision manipulating large quantum systems, while mastering individual degrees of freedom. It is thus timely to ask entirely new questions on the quantum/classical transition and to support these by experimental investigations of large entanglement. The vision of this project is to explore conceptually, experimentally and technologically the limits of large entanglement of macroscopically distinguishable quantum states. We propose to demonstrate entanglement between two or more macroscopic crystals with hundreds of entanglement bits (e-bits), hundred of thousands of excitations and billions of ions. For this purpose, we’ll use Neodymium doped YSO crystals and our AFC (Atomic Frequency Comb) protocol for multimode quantum memories.
Since entanglement is the signature of quantumness, this project will demonstrate “macroscopic” entanglement and help sharpening the meaning of “large” and “macroscopic”. By combining theory and experiments, questions like “What is large entanglement?” and “What deserves to be called entanglement between macroscopic systems?” will receive new insightful answers. This will deepen our understanding of Nature and in particular of the intricate meaning of meso- and macroscopic.
Two further goals of this project are to demonstrate large entanglement between two crystals separated by tens of kilometres, and to teleport many qubits stored in a crystal to a distant one.
Although this project is on fundamental questions, it will also contribute to improving the quantum memories required for continental scale ultra-secure quantum communications. We expect other surprising applications, in particular the high sensitivity of large entanglement to various decoherence mechanisms can be turned positively into quantum sensors."
Max ERC Funding
1 693 500 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym MEDEA
Project Mechanisms of Epigenetic regulation in Development, Evolution and Adaptation
Researcher (PI) Ulrich Grossniklaus
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Advanced Grant (AdG), LS2, ERC-2009-AdG
Summary Over the last decade epigenetic gene regulation has become a major focus of scientific research as it was shown to play an important role in normal plant and animal development, but also in the ontogeny of human disease. A role of epigenetic processes in evolution, however, has found little general support to date. The goal of this project is to understand the complex interplay of epigenetic mechanisms in plant development and evolution. Many of the approaches we use rely on the recent advances in sequencing technologies, which allow the analysis of molecular characters at an unprecedented level and speed. To achieve our goal, we will focus on two epigenetic paradigms. In Program A, we will focus on dissecting the mechanisms of genomic imprinting at the MEDEA (MEA) locus in Arabidopsis, which we will investigate using genetic, molecular, and innovative biochemical approaches to gain a comprehensive picture of the complex interplay of various epigenetic pathways. In program B, we will analyze the role of epigenetic change in adaptation and evolution using (i) an experimental selection approach in Arabidopsis, where genome-wide analyses of epigenetic modifications have become possible, and (ii) a stable, heritable, epigenetic change occurring in Mimulus populations. In this system, an epigenetic switch of the pollinator syndrome leads to reproductive isolation and, therefore, has an effect on population structure and thus the evolutionary trajectory. These experimental systems each offer unique opportunities to shed light onto the underlying mechanisms controlling epigenetic states. In combination with the new methodologies used, these analyses promise to provide step change in our understanding of epigenetic processes at the level of genes, organisms, and populations.
Summary
Over the last decade epigenetic gene regulation has become a major focus of scientific research as it was shown to play an important role in normal plant and animal development, but also in the ontogeny of human disease. A role of epigenetic processes in evolution, however, has found little general support to date. The goal of this project is to understand the complex interplay of epigenetic mechanisms in plant development and evolution. Many of the approaches we use rely on the recent advances in sequencing technologies, which allow the analysis of molecular characters at an unprecedented level and speed. To achieve our goal, we will focus on two epigenetic paradigms. In Program A, we will focus on dissecting the mechanisms of genomic imprinting at the MEDEA (MEA) locus in Arabidopsis, which we will investigate using genetic, molecular, and innovative biochemical approaches to gain a comprehensive picture of the complex interplay of various epigenetic pathways. In program B, we will analyze the role of epigenetic change in adaptation and evolution using (i) an experimental selection approach in Arabidopsis, where genome-wide analyses of epigenetic modifications have become possible, and (ii) a stable, heritable, epigenetic change occurring in Mimulus populations. In this system, an epigenetic switch of the pollinator syndrome leads to reproductive isolation and, therefore, has an effect on population structure and thus the evolutionary trajectory. These experimental systems each offer unique opportunities to shed light onto the underlying mechanisms controlling epigenetic states. In combination with the new methodologies used, these analyses promise to provide step change in our understanding of epigenetic processes at the level of genes, organisms, and populations.
Max ERC Funding
2 496 641 €
Duration
Start date: 2010-04-01, End date: 2015-12-31
Project acronym MODFLAT
Project "Moduli of flat connections, planar networks and associators"
Researcher (PI) Anton Alekseev
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Advanced Grant (AdG), PE1, ERC-2013-ADG
Summary "The project lies at the crossroads between three different topics in Mathematics: moduli spaces of flat connections on surfaces in Differential Geometry and Topology, the Kashiwara-Vergne problem and Drinfeld associators in Lie theory, and combinatorics of planar networks in the theory of Total Positivity.
The time is ripe to establish deep connections between these three theories. The main factors are the recent progress in the Kashiwara-Vergne theory (including the proof of the Kashiwara-Vergne conjecture by Alekseev-Meinrenken), the discovery of a link between the Horn problem on eigenvalues of sums of Hermitian matrices and planar network combinatorics, and intimate links with the Topological Quantum Field Theory shared by the three topics.
The scientific objectives of the project include answering the following questions:
1) To find a universal non-commutative volume formula for moduli of flat connections which would contain the Witten’s volume formula, the Verlinde formula, and the Moore-Nekrasov-Shatashvili formula as particular cases.
2) To show that all solutions of the Kashiwara-Vergne problem come from Drinfeld associators. If the answer is indeed positive, it will have applications to the study of the Gothendieck-Teichmüller Lie algebra grt.
3) To find a Gelfand-Zeiltin type integrable system for the symplectic group Sp(2n). This question is open since 1983.
To achieve these goals, one needs to use a multitude of techniques. Here we single out the ones developed by the author:
- Quasi-symplectic and quasi-Poisson Geometry and the theory of group valued moment maps.
- The linearization method for Poisson-Lie groups relating the additive problem z=x+y and the multiplicative problem Z=XY.
- Free Lie algebra approach to the Kashiwara-Vergne theory, including the non-commutative divergence and Jacobian cocylces.
- Non-abelian topical calculus which establishes a link between the multiplicative problem and combinatorics of planar networks."
Summary
"The project lies at the crossroads between three different topics in Mathematics: moduli spaces of flat connections on surfaces in Differential Geometry and Topology, the Kashiwara-Vergne problem and Drinfeld associators in Lie theory, and combinatorics of planar networks in the theory of Total Positivity.
The time is ripe to establish deep connections between these three theories. The main factors are the recent progress in the Kashiwara-Vergne theory (including the proof of the Kashiwara-Vergne conjecture by Alekseev-Meinrenken), the discovery of a link between the Horn problem on eigenvalues of sums of Hermitian matrices and planar network combinatorics, and intimate links with the Topological Quantum Field Theory shared by the three topics.
The scientific objectives of the project include answering the following questions:
1) To find a universal non-commutative volume formula for moduli of flat connections which would contain the Witten’s volume formula, the Verlinde formula, and the Moore-Nekrasov-Shatashvili formula as particular cases.
2) To show that all solutions of the Kashiwara-Vergne problem come from Drinfeld associators. If the answer is indeed positive, it will have applications to the study of the Gothendieck-Teichmüller Lie algebra grt.
3) To find a Gelfand-Zeiltin type integrable system for the symplectic group Sp(2n). This question is open since 1983.
To achieve these goals, one needs to use a multitude of techniques. Here we single out the ones developed by the author:
- Quasi-symplectic and quasi-Poisson Geometry and the theory of group valued moment maps.
- The linearization method for Poisson-Lie groups relating the additive problem z=x+y and the multiplicative problem Z=XY.
- Free Lie algebra approach to the Kashiwara-Vergne theory, including the non-commutative divergence and Jacobian cocylces.
- Non-abelian topical calculus which establishes a link between the multiplicative problem and combinatorics of planar networks."
Max ERC Funding
2 148 211 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym NuBSM
Project From Fermi to Planck : a bottom up approach
Researcher (PI) Mikhail SHAPOSHNIKOV
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Advanced Grant (AdG), PE2, ERC-2015-AdG
Summary The Standard Model of particle physics is a hugely successful theory that has been tested in experiments at ever increasing energies, culminating in the recent discovery of the Higgs boson. Nevertheless, some major riddles cannot be addressed by the Standard Model, such as neutrino oscillations, the existence of Dark Matter, the absence of antimatter in the Universe. New fundamental principles, interactions and unknown yet particles are required to address these questions. Much of the research done during the last three decades on physics ‘beyond the Standard Model’ (BSM) has been driven by attempts to find a ‘natural’ solution of the hierarchy problem: why the Planck and the electroweak scales are so different. The most popular approaches to this problem predict new particles with the masses right above the electroweak scale.
This project explores an alternative idea that the absence of new particles with masses between the electroweak and Planck scales, supplemented by extra symmetries (such as scale invariance) may itself explain why the mass of the Higgs boson is much smaller than the Planck mass. This calls for a solution of the BSM problems by extremely feebly interacting particles with masses below the electroweak scale. Along the same lines we also explore the possibility that cosmological inflation does not require a new field, but is driven by the Higgs field of the Standard Model.
The proposed model offers solutions for BSM puzzles and is among a few ones that can be tested with existing experimental technologies and are valid even if no evidence for new physics is found at the LHC.
Constructing such a theory requires consolidated efforts in domains of high-energy theory, particle physics phenomenology, physics of the early Universe, cosmology and astrophysics as well as analyses of the available data from previous experiments and from cosmology. We will make predictions and establish the sensitivity goals for future high intensity experiments.
Summary
The Standard Model of particle physics is a hugely successful theory that has been tested in experiments at ever increasing energies, culminating in the recent discovery of the Higgs boson. Nevertheless, some major riddles cannot be addressed by the Standard Model, such as neutrino oscillations, the existence of Dark Matter, the absence of antimatter in the Universe. New fundamental principles, interactions and unknown yet particles are required to address these questions. Much of the research done during the last three decades on physics ‘beyond the Standard Model’ (BSM) has been driven by attempts to find a ‘natural’ solution of the hierarchy problem: why the Planck and the electroweak scales are so different. The most popular approaches to this problem predict new particles with the masses right above the electroweak scale.
This project explores an alternative idea that the absence of new particles with masses between the electroweak and Planck scales, supplemented by extra symmetries (such as scale invariance) may itself explain why the mass of the Higgs boson is much smaller than the Planck mass. This calls for a solution of the BSM problems by extremely feebly interacting particles with masses below the electroweak scale. Along the same lines we also explore the possibility that cosmological inflation does not require a new field, but is driven by the Higgs field of the Standard Model.
The proposed model offers solutions for BSM puzzles and is among a few ones that can be tested with existing experimental technologies and are valid even if no evidence for new physics is found at the LHC.
Constructing such a theory requires consolidated efforts in domains of high-energy theory, particle physics phenomenology, physics of the early Universe, cosmology and astrophysics as well as analyses of the available data from previous experiments and from cosmology. We will make predictions and establish the sensitivity goals for future high intensity experiments.
Max ERC Funding
2 371 132 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym NucleolusChromatin
Project Analysis of the nucleolus in genome organization and function
Researcher (PI) Raffaella SANTORO
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Advanced Grant (AdG), LS2, ERC-2017-ADG
Summary In eukaryotic cells, the higher-order organization of genomes is functionally important to ensure correct execution of gene expression programs. For instance, as cells differentiate into specialized cell types, chromosomes undergo diverse structural and organizational changes that affect gene expression and other cellular functions. However, how this process is achieved is still poorly understood. The elucidation of the mechanisms that control the spatial architecture of the genome and its contribution to gene regulation is a key open issue in molecular biology, relevant for physiological and pathological processes.
Increasing evidence indicated that large-scale folding of chromatin may affect gene expression by locating genes to specific nuclear subcompartments that are either stimulatory or inhibitory to transcription. Nuclear periphery (NP) and nucleolus are two important nuclear landmarks where repressive chromatin domains are often located. The interaction of chromosomes with NP and nucleolus is thought to contribute to a basal chromosome architecture and genome function. However, while the role of NP in genome organization has been well documented, the function of the nucleolus remains yet elusive.
To fully understand how genome organization regulates chromatin and gene expression states, it is necessary to obtain a comprehensive functional map of genome compartmentalization. However, so far, only domains associating with NP (LADs) have been identified and characterized while nucleolar-associated domains (NADs) remained under-investigated. The aim of this project is to fill this gap by developing methods to identify and characterize NADs and analyse the role of the nucleolus in genome organization, moving toward the obtainment of a comprehensive functional map of genome compartmentalization for each cell state and providing novel insights into basic principles of genome organization and its role in gene expression and cell function that yet remain elusive.
Summary
In eukaryotic cells, the higher-order organization of genomes is functionally important to ensure correct execution of gene expression programs. For instance, as cells differentiate into specialized cell types, chromosomes undergo diverse structural and organizational changes that affect gene expression and other cellular functions. However, how this process is achieved is still poorly understood. The elucidation of the mechanisms that control the spatial architecture of the genome and its contribution to gene regulation is a key open issue in molecular biology, relevant for physiological and pathological processes.
Increasing evidence indicated that large-scale folding of chromatin may affect gene expression by locating genes to specific nuclear subcompartments that are either stimulatory or inhibitory to transcription. Nuclear periphery (NP) and nucleolus are two important nuclear landmarks where repressive chromatin domains are often located. The interaction of chromosomes with NP and nucleolus is thought to contribute to a basal chromosome architecture and genome function. However, while the role of NP in genome organization has been well documented, the function of the nucleolus remains yet elusive.
To fully understand how genome organization regulates chromatin and gene expression states, it is necessary to obtain a comprehensive functional map of genome compartmentalization. However, so far, only domains associating with NP (LADs) have been identified and characterized while nucleolar-associated domains (NADs) remained under-investigated. The aim of this project is to fill this gap by developing methods to identify and characterize NADs and analyse the role of the nucleolus in genome organization, moving toward the obtainment of a comprehensive functional map of genome compartmentalization for each cell state and providing novel insights into basic principles of genome organization and its role in gene expression and cell function that yet remain elusive.
Max ERC Funding
2 500 000 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym PDECP
Project Partial differential equations of Classical Physics
Researcher (PI) Demetrios Christodoulou
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE1, ERC-2009-AdG
Summary I shall pursue two projects both of which belong to the fields of partial differential equations, geometric analysis and mathematical physics. The first project, ``the shock development problem", belongs also to the field of fluid dynamics and aims at a full understanding of how, in the real world of 3 spatial dimensions, hydrodynamic shocks evolve, my previous work having analyzed in detail how they form. The second project, ``the formation of electromagnetic shocks in nonlinear media" aims at establishing how electromagnetic shocks form by the focusing of incoming electromagnetic wave pulses in a nonlinear medium. The case of an isotropic nonlinear dielectric will be studied first, to be followed by the case of a general isotropic medium. The methods of geometric analysis introduced in my previous work shall be employed, in particular the ``short pulse method" introduced in my work on the formation of black holes by the focusing of incoming gravitational waves in general relativity. The application of these methods to the problem for a general isotropic medium will require the development of new geometric structures. My three Ph. D. students shall purse the following three projects, belonging also to the fields of partial differential equations, geometric analysis and mathematical physics. The first project is in nonlinear elasticity. It is the study of the equilibrium configurations, in free space, of a crystalline solid in which a continuous distribution of dislocations is present, and aims at analyzing the relationship between the dislocation distribution and the resulting internal stress field. The second is in general relativity and aims at a theoretical understanding of the phenomena discovered by M. Choptuik in his numerical study of the gravitational collapse of a self-gravitating scalar field in spherical symmetry. The third is the study of hydrodynamic shock interactions and focusing in spherical symmetry.
Summary
I shall pursue two projects both of which belong to the fields of partial differential equations, geometric analysis and mathematical physics. The first project, ``the shock development problem", belongs also to the field of fluid dynamics and aims at a full understanding of how, in the real world of 3 spatial dimensions, hydrodynamic shocks evolve, my previous work having analyzed in detail how they form. The second project, ``the formation of electromagnetic shocks in nonlinear media" aims at establishing how electromagnetic shocks form by the focusing of incoming electromagnetic wave pulses in a nonlinear medium. The case of an isotropic nonlinear dielectric will be studied first, to be followed by the case of a general isotropic medium. The methods of geometric analysis introduced in my previous work shall be employed, in particular the ``short pulse method" introduced in my work on the formation of black holes by the focusing of incoming gravitational waves in general relativity. The application of these methods to the problem for a general isotropic medium will require the development of new geometric structures. My three Ph. D. students shall purse the following three projects, belonging also to the fields of partial differential equations, geometric analysis and mathematical physics. The first project is in nonlinear elasticity. It is the study of the equilibrium configurations, in free space, of a crystalline solid in which a continuous distribution of dislocations is present, and aims at analyzing the relationship between the dislocation distribution and the resulting internal stress field. The second is in general relativity and aims at a theoretical understanding of the phenomena discovered by M. Choptuik in his numerical study of the gravitational collapse of a self-gravitating scalar field in spherical symmetry. The third is the study of hydrodynamic shock interactions and focusing in spherical symmetry.
Max ERC Funding
1 278 000 €
Duration
Start date: 2010-03-01, End date: 2015-02-28
Project acronym PertQCD
Project Automatization of perturbative QCD at very high orders.
Researcher (PI) Charalampos ANASTASIOU
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), PE2, ERC-2015-AdG
Summary In recent months, we broke new ground in perturbative Quantum Chromodynamics computing for the first time a physical cross-section of a hadron collider process - Higgs production - at the fourth order in the strong coupling constant expansion. This breakthrough improved the perturbative precision of a fundamental cross-section by a factor of four, paving the way for a very precise testing of the Standard Model theory against LHC data.
The aim of our proposal is to fully automate all calculations which are needed for LHC and future collider physics at similarly high perturbative orders. Our work will improve the precision of theoretical predictions across the spectrum of LHC phenomenology, matching or superseding the accuracy of
experimental measurements. In turn, we will be able to draw firm conclusions about the validity of theories which aspire to describe nature at TeV energies and search confidently for signals of new physics through precision measurements at the LHC.
Summary
In recent months, we broke new ground in perturbative Quantum Chromodynamics computing for the first time a physical cross-section of a hadron collider process - Higgs production - at the fourth order in the strong coupling constant expansion. This breakthrough improved the perturbative precision of a fundamental cross-section by a factor of four, paving the way for a very precise testing of the Standard Model theory against LHC data.
The aim of our proposal is to fully automate all calculations which are needed for LHC and future collider physics at similarly high perturbative orders. Our work will improve the precision of theoretical predictions across the spectrum of LHC phenomenology, matching or superseding the accuracy of
experimental measurements. In turn, we will be able to draw firm conclusions about the validity of theories which aspire to describe nature at TeV energies and search confidently for signals of new physics through precision measurements at the LHC.
Max ERC Funding
2 045 095 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym PROTEOMICS V3.0
Project Proteomics v3.0: Development, Implementation and Dissemination of a Third Generation Proteomics Technology
Researcher (PI) Rudolf Aebersold
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), LS2, ERC-2008-AdG
Summary Quantitative proteomics is a key technology for the life sciences in general and for systems biology in particular. So far, however, technical limitations have made it impossible to analyze the complete proteome of any species. It is the general goal of this proposal to develop, implement, apply and disseminate a new proteomic strategy that has the potential to generate quantitative proteomic datasets at an unprecedented depth, throughput, accuracy and robustness. Specifically, the new technology will identify and quantify every protein in a proteome. The title of the project Proteomics v3.0 was chosen to indicate the transformation of proteomics into its third phase, after 2D gel electrophoresis and LC-MS/MS based shotgun proteomics. Proteomics v3.0 is based on two sequential steps, emulating the strategy that has been immensely successful in the genomic sciences. In the first step the proteomic space is completely mapped out to generate a proteomic resource that is akin to the genomic sequence database. In the second step rapid and accurate assays will be developed to unambiguously identify and quantify any protein of the respective proteome in a multitude of samples. These assays will be made publicly accessible to support quantitative proteomic studies in the respective species. The strategy will first be implemented and tested in the yeast S. cerevisiae. In a later stage of the project it will be extended to the more complicated human proteome and include the development of assays that also probe the state of modification, splice forms and other types of protein variants generated by a specific open reading frame. Overall, the project will transform quantitative proteomics from a highly specialized technology practiced at a high level in a few laboratories worldwide into a commodity technology accessible, in principle to every group.
Summary
Quantitative proteomics is a key technology for the life sciences in general and for systems biology in particular. So far, however, technical limitations have made it impossible to analyze the complete proteome of any species. It is the general goal of this proposal to develop, implement, apply and disseminate a new proteomic strategy that has the potential to generate quantitative proteomic datasets at an unprecedented depth, throughput, accuracy and robustness. Specifically, the new technology will identify and quantify every protein in a proteome. The title of the project Proteomics v3.0 was chosen to indicate the transformation of proteomics into its third phase, after 2D gel electrophoresis and LC-MS/MS based shotgun proteomics. Proteomics v3.0 is based on two sequential steps, emulating the strategy that has been immensely successful in the genomic sciences. In the first step the proteomic space is completely mapped out to generate a proteomic resource that is akin to the genomic sequence database. In the second step rapid and accurate assays will be developed to unambiguously identify and quantify any protein of the respective proteome in a multitude of samples. These assays will be made publicly accessible to support quantitative proteomic studies in the respective species. The strategy will first be implemented and tested in the yeast S. cerevisiae. In a later stage of the project it will be extended to the more complicated human proteome and include the development of assays that also probe the state of modification, splice forms and other types of protein variants generated by a specific open reading frame. Overall, the project will transform quantitative proteomics from a highly specialized technology practiced at a high level in a few laboratories worldwide into a commodity technology accessible, in principle to every group.
Max ERC Funding
2 400 000 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
Project acronym PROTEOMICS4D
Project Proteomics 4D: The proteome in context
Researcher (PI) Rudolf Aebersold
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Advanced Grant (AdG), LS2, ERC-2014-ADG
Summary Elements operating in the context of a system generate results that are different from the simple addition of the results of each element. This notion is one of the basic tenants of systems science. In systems biology/medicine complex (disease) phenotypes arise from multiple interacting factors, specifically proteins. Yet, the biochemical and mechanistic base of complex phenotypes remain elusive.
An array of powerful genomic technologies including GWAS, WGS, transcriptomics, epigenetic analyses and proteomics have identified numerous factors that contribute to complex phenotypes. It can be expected that over the next few years, genetic factors contributing to specific complex phenotypes will be comprehensively identified, while their interactions will remain elusive.
The project “Proteomics 4D: The proteome in context “explores the concept, that complex phenotypes arise from the perturbation of modules of interacting proteins and that these modules integrate seemingly independent genomic variants into a single biochemical response. We will develop and apply a generic technology to directly measure the composition, topology and structure of wild type and genetically perturbed protein modules and relate structural changes to their functional output.
This will be achieved by a the integration of quantitative proteomic and phosphoproteomic technologies determining molecular phenotypes, and hybrid structural methods consisting of chemical cross-linking and mass spectrometry, cryoEM and computational data integration to probe structural perturbations.
The project will focus initially on the structural and functional effects of cancer associated mutations in protein kinase modules and then generalize to study perturbed modules in any tissue and disease state. The resources supporting this technology will be disseminated to catalyze a broad transformation of biology and molecular medicine towards the analysis of the proteome as a modular entity, the proteome in context.
Summary
Elements operating in the context of a system generate results that are different from the simple addition of the results of each element. This notion is one of the basic tenants of systems science. In systems biology/medicine complex (disease) phenotypes arise from multiple interacting factors, specifically proteins. Yet, the biochemical and mechanistic base of complex phenotypes remain elusive.
An array of powerful genomic technologies including GWAS, WGS, transcriptomics, epigenetic analyses and proteomics have identified numerous factors that contribute to complex phenotypes. It can be expected that over the next few years, genetic factors contributing to specific complex phenotypes will be comprehensively identified, while their interactions will remain elusive.
The project “Proteomics 4D: The proteome in context “explores the concept, that complex phenotypes arise from the perturbation of modules of interacting proteins and that these modules integrate seemingly independent genomic variants into a single biochemical response. We will develop and apply a generic technology to directly measure the composition, topology and structure of wild type and genetically perturbed protein modules and relate structural changes to their functional output.
This will be achieved by a the integration of quantitative proteomic and phosphoproteomic technologies determining molecular phenotypes, and hybrid structural methods consisting of chemical cross-linking and mass spectrometry, cryoEM and computational data integration to probe structural perturbations.
The project will focus initially on the structural and functional effects of cancer associated mutations in protein kinase modules and then generalize to study perturbed modules in any tissue and disease state. The resources supporting this technology will be disseminated to catalyze a broad transformation of biology and molecular medicine towards the analysis of the proteome as a modular entity, the proteome in context.
Max ERC Funding
2 208 150 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
