Project acronym ABEL
Project "Alpha-helical Barrels: Exploring, Understanding and Exploiting a New Class of Protein Structure"
Researcher (PI) Derek Neil Woolfson
Host Institution (HI) UNIVERSITY OF BRISTOL
Country United Kingdom
Call Details Advanced Grant (AdG), LS9, ERC-2013-ADG
Summary "Recently through de novo peptide design, we have discovered and presented a new protein structure. This is an all-parallel, 6-helix bundle with a continuous central channel of 0.5 – 0.6 nm diameter. We posit that this is one of a broader class of protein structures that we call the alpha-helical barrels. Here, in three Work Packages, we propose to explore these structures and to develop protein functions within them. First, through a combination of computer-aided design, peptide synthesis and thorough biophysical characterization, we will examine the extents and limits of the alpha-helical-barrel structures. Whilst this is curiosity driven research, it also has practical consequences for the studies that will follow; that is, alpha-helical barrels made from increasing numbers of helices have channels or pores that increase in a predictable way. Second, we will use rational and empirical design approaches to engineer a range of functions within these cavities, including binding capabilities and enzyme-like activities. Finally, and taking the programme into another ambitious area, we will use the alpha-helical barrels to template other folds that are otherwise difficult to design and engineer, notably beta-barrels that insert into membranes to render ion-channel and sensor functions."
Summary
"Recently through de novo peptide design, we have discovered and presented a new protein structure. This is an all-parallel, 6-helix bundle with a continuous central channel of 0.5 – 0.6 nm diameter. We posit that this is one of a broader class of protein structures that we call the alpha-helical barrels. Here, in three Work Packages, we propose to explore these structures and to develop protein functions within them. First, through a combination of computer-aided design, peptide synthesis and thorough biophysical characterization, we will examine the extents and limits of the alpha-helical-barrel structures. Whilst this is curiosity driven research, it also has practical consequences for the studies that will follow; that is, alpha-helical barrels made from increasing numbers of helices have channels or pores that increase in a predictable way. Second, we will use rational and empirical design approaches to engineer a range of functions within these cavities, including binding capabilities and enzyme-like activities. Finally, and taking the programme into another ambitious area, we will use the alpha-helical barrels to template other folds that are otherwise difficult to design and engineer, notably beta-barrels that insert into membranes to render ion-channel and sensor functions."
Max ERC Funding
2 467 844 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym ADREEM
Project Adding Another Dimension – Arrays of 3D Bio-Responsive Materials
Researcher (PI) Mark Bradley
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Country United Kingdom
Call Details Advanced Grant (AdG), LS9, ERC-2013-ADG
Summary This proposal is focused in the areas of chemical medicine and chemical biology with the key drivers being the discovery and development of new materials that have practical functionality and application. The project will enable the fabrication of thousands of three-dimensional “smart-polymers” that will allow: (i). The precise and controlled release of drugs upon the addition of either a small molecule trigger or in response to disease, (ii). The discovery of materials that control and manipulate cells with the identification of scaffolds that provide the necessary biochemical cues for directing cell fate and drive tissue regeneration and (iii). The development of new classes of “smart-polymers” able, in real-time, to sense and report bacterial contamination. The newly discovered materials will find multiple biomedical applications in regenerative medicine and biotechnology ranging from 3D cell culture, bone repair and niche stabilisation to bacterial sensing/removal, while offering a new paradigm in drug delivery with biomarker triggered drug release.
Summary
This proposal is focused in the areas of chemical medicine and chemical biology with the key drivers being the discovery and development of new materials that have practical functionality and application. The project will enable the fabrication of thousands of three-dimensional “smart-polymers” that will allow: (i). The precise and controlled release of drugs upon the addition of either a small molecule trigger or in response to disease, (ii). The discovery of materials that control and manipulate cells with the identification of scaffolds that provide the necessary biochemical cues for directing cell fate and drive tissue regeneration and (iii). The development of new classes of “smart-polymers” able, in real-time, to sense and report bacterial contamination. The newly discovered materials will find multiple biomedical applications in regenerative medicine and biotechnology ranging from 3D cell culture, bone repair and niche stabilisation to bacterial sensing/removal, while offering a new paradigm in drug delivery with biomarker triggered drug release.
Max ERC Funding
2 310 884 €
Duration
Start date: 2014-11-01, End date: 2019-10-31
Project acronym AFMIDMOA
Project "Applying Fundamental Mathematics in Discrete Mathematics, Optimization, and Algorithmics"
Researcher (PI) Alexander Schrijver
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Country Netherlands
Call Details Advanced Grant (AdG), PE1, ERC-2013-ADG
Summary "This proposal aims at strengthening the connections between more fundamentally oriented areas of mathematics like algebra, geometry, analysis, and topology, and the more applied oriented and more recently emerging disciplines of discrete mathematics, optimization, and algorithmics.
The overall goal of the project is to obtain, with methods from fundamental mathematics, new effective tools to unravel the complexity of structures like graphs, networks, codes, knots, polynomials, and tensors, and to get a grip on such complex structures by new efficient characterizations, sharper bounds, and faster algorithms.
In the last few years, there have been several new developments where methods from representation theory, invariant theory, algebraic geometry, measure theory, functional analysis, and topology found new applications in discrete mathematics and optimization, both theoretically and algorithmically. Among the typical application areas are networks, coding, routing, timetabling, statistical and quantum physics, and computer science.
The project focuses in particular on:
A. Understanding partition functions with invariant theory and algebraic geometry
B. Graph limits, regularity, Hilbert spaces, and low rank approximation of polynomials
C. Reducing complexity in optimization by exploiting symmetry with representation theory
D. Reducing complexity in discrete optimization by homotopy and cohomology
These research modules are interconnected by themes like symmetry, regularity, and complexity, and by common methods from algebra, analysis, geometry, and topology."
Summary
"This proposal aims at strengthening the connections between more fundamentally oriented areas of mathematics like algebra, geometry, analysis, and topology, and the more applied oriented and more recently emerging disciplines of discrete mathematics, optimization, and algorithmics.
The overall goal of the project is to obtain, with methods from fundamental mathematics, new effective tools to unravel the complexity of structures like graphs, networks, codes, knots, polynomials, and tensors, and to get a grip on such complex structures by new efficient characterizations, sharper bounds, and faster algorithms.
In the last few years, there have been several new developments where methods from representation theory, invariant theory, algebraic geometry, measure theory, functional analysis, and topology found new applications in discrete mathematics and optimization, both theoretically and algorithmically. Among the typical application areas are networks, coding, routing, timetabling, statistical and quantum physics, and computer science.
The project focuses in particular on:
A. Understanding partition functions with invariant theory and algebraic geometry
B. Graph limits, regularity, Hilbert spaces, and low rank approximation of polynomials
C. Reducing complexity in optimization by exploiting symmetry with representation theory
D. Reducing complexity in discrete optimization by homotopy and cohomology
These research modules are interconnected by themes like symmetry, regularity, and complexity, and by common methods from algebra, analysis, geometry, and topology."
Max ERC Funding
2 001 598 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym AMAIZE
Project Atlas of leaf growth regulatory networks in MAIZE
Researcher (PI) Dirk, Gustaaf Inze
Host Institution (HI) VIB VZW
Country Belgium
Call Details Advanced Grant (AdG), LS9, ERC-2013-ADG
Summary "Understanding how organisms regulate size is one of the most fascinating open questions in biology. The aim of the AMAIZE project is to unravel how growth of maize leaves is controlled. Maize leaf development offers great opportunities to study the dynamics of growth regulatory networks, essentially because leaf development is a linear system with cell division at the leaf basis followed by cell expansion and maturation. Furthermore, the growth zone is relatively large allowing easy access of tissues at different positions. Four different perturbations of maize leaf size will be analyzed with cellular resolution: wild-type and plants having larger leaves (as a consequence of GA20OX1 overexpression), both grown under either well-watered or mild drought conditions. Firstly, a 3D cellular map of the growth zone of the fourth leaf will be made. RNA-SEQ of three different tissues (adaxial- and abaxial epidermis; mesophyll) obtained by laser dissection with an interval of 2.5 mm along the growth zone will allow for the analysis of the transcriptome with high resolution. Additionally, the composition of fifty selected growth regulatory protein complexes and DNA targets of transcription factors will be determined with an interval of 5 mm along the growth zone. Computational methods will be used to construct comprehensive integrative maps of the cellular and molecular processes occurring along the growth zone. Finally, selected regulatory nodes of the growth regulatory networks will be further functionally analyzed using a transactivation system in maize.
AMAIZE opens up new perspectives for the identification of optimal growth regulatory networks that can be selected for by advanced breeding or for which more robust variants (e.g. reduced susceptibility to drought) can be obtained through genetic engineering. The ability to improve the growth of maize and in analogy other cereals could have a high impact in providing food security"
Summary
"Understanding how organisms regulate size is one of the most fascinating open questions in biology. The aim of the AMAIZE project is to unravel how growth of maize leaves is controlled. Maize leaf development offers great opportunities to study the dynamics of growth regulatory networks, essentially because leaf development is a linear system with cell division at the leaf basis followed by cell expansion and maturation. Furthermore, the growth zone is relatively large allowing easy access of tissues at different positions. Four different perturbations of maize leaf size will be analyzed with cellular resolution: wild-type and plants having larger leaves (as a consequence of GA20OX1 overexpression), both grown under either well-watered or mild drought conditions. Firstly, a 3D cellular map of the growth zone of the fourth leaf will be made. RNA-SEQ of three different tissues (adaxial- and abaxial epidermis; mesophyll) obtained by laser dissection with an interval of 2.5 mm along the growth zone will allow for the analysis of the transcriptome with high resolution. Additionally, the composition of fifty selected growth regulatory protein complexes and DNA targets of transcription factors will be determined with an interval of 5 mm along the growth zone. Computational methods will be used to construct comprehensive integrative maps of the cellular and molecular processes occurring along the growth zone. Finally, selected regulatory nodes of the growth regulatory networks will be further functionally analyzed using a transactivation system in maize.
AMAIZE opens up new perspectives for the identification of optimal growth regulatory networks that can be selected for by advanced breeding or for which more robust variants (e.g. reduced susceptibility to drought) can be obtained through genetic engineering. The ability to improve the growth of maize and in analogy other cereals could have a high impact in providing food security"
Max ERC Funding
2 418 429 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym AMAREC
Project Amenability, Approximation and Reconstruction
Researcher (PI) Wilhelm WINTER
Host Institution (HI) WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Country Germany
Call Details Advanced Grant (AdG), PE1, ERC-2018-ADG
Summary Algebras of operators on Hilbert spaces were originally introduced as the right framework for the mathematical description of quantum mechanics. In modern mathematics the scope has much broadened due to the highly versatile nature of operator algebras. They are particularly useful in the analysis of groups and their actions. Amenability is a finiteness property which occurs in many different contexts and which can be characterised in many different ways. We will analyse amenability in terms of approximation properties, in the frameworks of abstract C*-algebras, of topological dynamical systems, and of discrete groups. Such approximation properties will serve as bridging devices between these setups, and they will be used to systematically recover geometric information about the underlying structures. When passing from groups, and more generally from dynamical systems, to operator algebras, one loses information, but one gains new tools to isolate and analyse pertinent properties of the underlying structure. We will mostly be interested in the topological setting, and in the associated C*-algebras. Amenability of groups or of dynamical systems then translates into the completely positive approximation property. Systems of completely positive approximations store all the essential data about a C*-algebra, and sometimes one can arrange the systems so that one can directly read of such information. For transformation group C*-algebras, one can achieve this by using approximation properties of the underlying dynamics. To some extent one can even go back, and extract dynamical approximation properties from completely positive approximations of the C*-algebra. This interplay between approximation properties in topological dynamics and in noncommutative topology carries a surprisingly rich structure. It connects directly to the heart of the classification problem for nuclear C*-algebras on the one hand, and to central open questions on amenable dynamics on the other.
Summary
Algebras of operators on Hilbert spaces were originally introduced as the right framework for the mathematical description of quantum mechanics. In modern mathematics the scope has much broadened due to the highly versatile nature of operator algebras. They are particularly useful in the analysis of groups and their actions. Amenability is a finiteness property which occurs in many different contexts and which can be characterised in many different ways. We will analyse amenability in terms of approximation properties, in the frameworks of abstract C*-algebras, of topological dynamical systems, and of discrete groups. Such approximation properties will serve as bridging devices between these setups, and they will be used to systematically recover geometric information about the underlying structures. When passing from groups, and more generally from dynamical systems, to operator algebras, one loses information, but one gains new tools to isolate and analyse pertinent properties of the underlying structure. We will mostly be interested in the topological setting, and in the associated C*-algebras. Amenability of groups or of dynamical systems then translates into the completely positive approximation property. Systems of completely positive approximations store all the essential data about a C*-algebra, and sometimes one can arrange the systems so that one can directly read of such information. For transformation group C*-algebras, one can achieve this by using approximation properties of the underlying dynamics. To some extent one can even go back, and extract dynamical approximation properties from completely positive approximations of the C*-algebra. This interplay between approximation properties in topological dynamics and in noncommutative topology carries a surprisingly rich structure. It connects directly to the heart of the classification problem for nuclear C*-algebras on the one hand, and to central open questions on amenable dynamics on the other.
Max ERC Funding
1 596 017 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym ANDLICA
Project Anderson Localization of Light by Cold Atoms
Researcher (PI) Robin KAISER
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Country France
Call Details Advanced Grant (AdG), PE2, ERC-2018-ADG
Summary I propose to use large clouds of cold Ytterbium atoms to observe Anderson localization of light in three dimensions, which has challenged theoreticians and experimentalists for many decades.
After the prediction by Anderson of a disorder-induced conductor to insulator transition for electrons, light has been proposed as ideal non interacting waves to explore coherent transport properties in the absence of interactions. The development in experiments and theory over the past several years have shown a route towards the experimental realization of this phase transition.
Previous studies on Anderson localization of light using semiconductor powders or dielectric particles have shown that intrinsic material properties, such as absorption or inelastic scattering of light, need to be taken into account in the interpretation of experimental signatures of Anderson localization. Laser-cooled clouds of atoms avoid the problems of samples used so far to study Anderson localization of light. Ab initio theoretical models, available for cold Ytterbium atoms, have shown that the mere high spatial density of the scattering sample is not sufficient to allow for Anderson localization of photons in three dimensions, but that an additional magnetic field or additional disorder on the level shifts can induce a phase transition in three dimensions.
The role of disorder in atom-light interactions has important consequences for the next generation of high precision atomic clocks and quantum memories. By connecting the mesoscopic physics approach to quantum optics and cooperative scattering, this project will allow better control of cold atoms as building blocks of future quantum technologies. Time-resolved transport experiments will connect super- and subradiant assisted transmission with the extended and localized eigenstates of the system.
Having pioneered studies on weak localization and cooperative scattering enables me to diagnostic strong localization of light by cold atoms.
Summary
I propose to use large clouds of cold Ytterbium atoms to observe Anderson localization of light in three dimensions, which has challenged theoreticians and experimentalists for many decades.
After the prediction by Anderson of a disorder-induced conductor to insulator transition for electrons, light has been proposed as ideal non interacting waves to explore coherent transport properties in the absence of interactions. The development in experiments and theory over the past several years have shown a route towards the experimental realization of this phase transition.
Previous studies on Anderson localization of light using semiconductor powders or dielectric particles have shown that intrinsic material properties, such as absorption or inelastic scattering of light, need to be taken into account in the interpretation of experimental signatures of Anderson localization. Laser-cooled clouds of atoms avoid the problems of samples used so far to study Anderson localization of light. Ab initio theoretical models, available for cold Ytterbium atoms, have shown that the mere high spatial density of the scattering sample is not sufficient to allow for Anderson localization of photons in three dimensions, but that an additional magnetic field or additional disorder on the level shifts can induce a phase transition in three dimensions.
The role of disorder in atom-light interactions has important consequences for the next generation of high precision atomic clocks and quantum memories. By connecting the mesoscopic physics approach to quantum optics and cooperative scattering, this project will allow better control of cold atoms as building blocks of future quantum technologies. Time-resolved transport experiments will connect super- and subradiant assisted transmission with the extended and localized eigenstates of the system.
Having pioneered studies on weak localization and cooperative scattering enables me to diagnostic strong localization of light by cold atoms.
Max ERC Funding
2 490 717 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym ANOBEST
Project Structure function and pharmacology of calcium-activated chloride channels: Anoctamins and Bestrophins
Researcher (PI) Raimund Dutzler
Host Institution (HI) University of Zurich
Country Switzerland
Call Details Advanced Grant (AdG), LS1, ERC-2013-ADG
Summary Calcium-activated chloride channels (CaCCs) play key roles in a range of physiological processes such as the control of membrane excitability, photoreception and epithelial secretion. Although the importance of these channels has been recognized for more than 30 years their molecular identity remained obscure. The recent discovery of two protein families encoding for CaCCs, Anoctamins and Bestrophins, was a scientific breakthrough that has provided first insight into two novel ion channel architectures. Within this proposal we aim to determine the first high resolution structures of members of both families and study their functional behavior by an interdisciplinary approach combining biochemistry, X-ray crystallography and electrophysiology. The structural investigation of eukaryotic membrane proteins is extremely challenging and will require us to investigate large numbers of candidates to single out family members with superior biochemical properties. During the last year we have made large progress in this direction. By screening numerous eukaryotic Anoctamins and prokaryotic Bestrophins we have identified well-behaved proteins for both families, which were successfully scaled-up and purified. Additional family members will be identified within the course of the project. For these stable proteins we plan to grow crystals diffracting to high resolution and to proceed with structure determination. With first structural information in hand we will perform detailed functional studies using electrophysiology and complementary biophysical techniques to gain mechanistic insight into ion permeation and gating. As the pharmacology of both families is still in its infancy we will in later stages also engage in the identification and characterization of inhibitors and activators of Anoctamins and Bestrophins to open up a field that may ultimately lead to the discovery of novel therapeutic strategies targeting calcium-activated chloride channels.
Summary
Calcium-activated chloride channels (CaCCs) play key roles in a range of physiological processes such as the control of membrane excitability, photoreception and epithelial secretion. Although the importance of these channels has been recognized for more than 30 years their molecular identity remained obscure. The recent discovery of two protein families encoding for CaCCs, Anoctamins and Bestrophins, was a scientific breakthrough that has provided first insight into two novel ion channel architectures. Within this proposal we aim to determine the first high resolution structures of members of both families and study their functional behavior by an interdisciplinary approach combining biochemistry, X-ray crystallography and electrophysiology. The structural investigation of eukaryotic membrane proteins is extremely challenging and will require us to investigate large numbers of candidates to single out family members with superior biochemical properties. During the last year we have made large progress in this direction. By screening numerous eukaryotic Anoctamins and prokaryotic Bestrophins we have identified well-behaved proteins for both families, which were successfully scaled-up and purified. Additional family members will be identified within the course of the project. For these stable proteins we plan to grow crystals diffracting to high resolution and to proceed with structure determination. With first structural information in hand we will perform detailed functional studies using electrophysiology and complementary biophysical techniques to gain mechanistic insight into ion permeation and gating. As the pharmacology of both families is still in its infancy we will in later stages also engage in the identification and characterization of inhibitors and activators of Anoctamins and Bestrophins to open up a field that may ultimately lead to the discovery of novel therapeutic strategies targeting calcium-activated chloride channels.
Max ERC Funding
2 176 000 €
Duration
Start date: 2014-02-01, End date: 2020-01-31
Project acronym ARGO
Project The Quest of the Argonautes - from Myth to Reality
Researcher (PI) JOHN VAN DER OOST
Host Institution (HI) WAGENINGEN UNIVERSITY
Country Netherlands
Call Details Advanced Grant (AdG), LS1, ERC-2018-ADG
Summary Argonaute nucleases are key players of the eukaryotic RNA interference (RNAi) system. Using small RNA guides, these Argonaute (Ago) proteins specifically target complementary RNA molecules, resulting in regulation of a wide range of crucial processes, including chromosome organization, gene expression and anti-virus defence. Since 2010, my research team has studied closely-related prokaryotic Argonaute (pAgo) variants. This has revealed spectacular mechanistic variations: several thermophilic pAgos catalyse DNA-guided cleavage of double stranded DNA, but only at elevated temperatures. Interestingly, a recently discovered mesophilic Argonaute (CbAgo) can generate double strand DNA breaks at moderate temperatures, providing an excellent basis for this ARGO project. In addition, genome analysis has revealed many distantly-related Argonaute variants, often with unique domain architectures. Hence, the currently known Argonaute homologs are just the tip of the iceberg, and the stage is set for making a big leap in the exploration of the Argonaute family. Initially we will dissect the molecular basis of functional and mechanistic features of uncharacterized natural Argonaute variants, both in eukaryotes (the presence of an Ago-like subunit in the Mediator complex, strongly suggests a regulatory role of an elusive non-coding RNA ligand) and in prokaryotes (selected Ago variants possess distinct domains indicating novel functionalities). After their thorough biochemical characterization, I aim at engineering the functionality of the aforementioned CbAgo through an integrated rational & random approach, i.e. by tinkering of domains, and by an unprecedented in vitro laboratory evolution approach. Eventually, natural & synthetic Argonautes will be selected for their exploitation, and used for developing original genome editing applications (from silencing to base editing). Embarking on this ambitious ARGO expedition will lead us to many exciting discoveries.
Summary
Argonaute nucleases are key players of the eukaryotic RNA interference (RNAi) system. Using small RNA guides, these Argonaute (Ago) proteins specifically target complementary RNA molecules, resulting in regulation of a wide range of crucial processes, including chromosome organization, gene expression and anti-virus defence. Since 2010, my research team has studied closely-related prokaryotic Argonaute (pAgo) variants. This has revealed spectacular mechanistic variations: several thermophilic pAgos catalyse DNA-guided cleavage of double stranded DNA, but only at elevated temperatures. Interestingly, a recently discovered mesophilic Argonaute (CbAgo) can generate double strand DNA breaks at moderate temperatures, providing an excellent basis for this ARGO project. In addition, genome analysis has revealed many distantly-related Argonaute variants, often with unique domain architectures. Hence, the currently known Argonaute homologs are just the tip of the iceberg, and the stage is set for making a big leap in the exploration of the Argonaute family. Initially we will dissect the molecular basis of functional and mechanistic features of uncharacterized natural Argonaute variants, both in eukaryotes (the presence of an Ago-like subunit in the Mediator complex, strongly suggests a regulatory role of an elusive non-coding RNA ligand) and in prokaryotes (selected Ago variants possess distinct domains indicating novel functionalities). After their thorough biochemical characterization, I aim at engineering the functionality of the aforementioned CbAgo through an integrated rational & random approach, i.e. by tinkering of domains, and by an unprecedented in vitro laboratory evolution approach. Eventually, natural & synthetic Argonautes will be selected for their exploitation, and used for developing original genome editing applications (from silencing to base editing). Embarking on this ambitious ARGO expedition will lead us to many exciting discoveries.
Max ERC Funding
2 177 158 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym AtomicGaugeSimulator
Project Classical and Atomic Quantum Simulation of Gauge Theories in Particle and Condensed Matter Physics
Researcher (PI) Uwe-Jens Richard Christian Wiese
Host Institution (HI) UNIVERSITAET BERN
Country Switzerland
Call Details Advanced Grant (AdG), PE2, ERC-2013-ADG
Summary Gauge theories play a central role in particle and condensed matter physics. Heavy-ion collisions explore the strong dynamics of quarks and gluons, which also governs the deep interior of neutron stars, while strongly correlated electrons determine the physics of high-temperature superconductors and spin liquids. Numerical simulations of such systems are often hindered by sign problems. In quantum link models - an alternative formulation of gauge theories developed by the applicant - gauge fields emerge from discrete quantum variables. In the past year, in close collaboration with atomic physicists, we have established quantum link models as a framework for the atomic quantum simulation of dynamical gauge fields. Abelian gauge theories can be realized with Bose-Fermi mixtures of ultracold atoms in an optical lattice, while non-Abelian gauge fields arise from fermionic constituents embodied by alkaline-earth atoms. Quantum simulators, which do not suffer from the sign problem, shall be constructed to address non-trivial dynamics, including quantum phase transitions in spin liquids, the real-time dynamics of confining strings as well as of chiral symmetry restoration at finite temperature and baryon density, baryon superfluidity, or color-flavor locking. New classical simulation algorithms shall be developed in order to solve severe sign problems, to investigate confining gauge theories, and to validate the proposed quantum simulators. Starting from U(1) and SU(2) gauge theories, an atomic physics tool box shall be developed for quantum simulation of gauge theories of increasing complexity, ultimately aiming at 4-d Quantum Chromodynamics (QCD). This project is based on innovative ideas from particle, condensed matter, and computational physics, and requires an interdisciplinary team of researchers. It has the potential to drastically increase the power of simulations and to address very challenging problems that cannot be solved with classical simulation methods.
Summary
Gauge theories play a central role in particle and condensed matter physics. Heavy-ion collisions explore the strong dynamics of quarks and gluons, which also governs the deep interior of neutron stars, while strongly correlated electrons determine the physics of high-temperature superconductors and spin liquids. Numerical simulations of such systems are often hindered by sign problems. In quantum link models - an alternative formulation of gauge theories developed by the applicant - gauge fields emerge from discrete quantum variables. In the past year, in close collaboration with atomic physicists, we have established quantum link models as a framework for the atomic quantum simulation of dynamical gauge fields. Abelian gauge theories can be realized with Bose-Fermi mixtures of ultracold atoms in an optical lattice, while non-Abelian gauge fields arise from fermionic constituents embodied by alkaline-earth atoms. Quantum simulators, which do not suffer from the sign problem, shall be constructed to address non-trivial dynamics, including quantum phase transitions in spin liquids, the real-time dynamics of confining strings as well as of chiral symmetry restoration at finite temperature and baryon density, baryon superfluidity, or color-flavor locking. New classical simulation algorithms shall be developed in order to solve severe sign problems, to investigate confining gauge theories, and to validate the proposed quantum simulators. Starting from U(1) and SU(2) gauge theories, an atomic physics tool box shall be developed for quantum simulation of gauge theories of increasing complexity, ultimately aiming at 4-d Quantum Chromodynamics (QCD). This project is based on innovative ideas from particle, condensed matter, and computational physics, and requires an interdisciplinary team of researchers. It has the potential to drastically increase the power of simulations and to address very challenging problems that cannot be solved with classical simulation methods.
Max ERC Funding
1 975 242 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym BIRTOACTION
Project From birth to action: regulation of gene expression through transcription complex biogenesis
Researcher (PI) Laszlo Tora
Host Institution (HI) CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE
Country France
Call Details Advanced Grant (AdG), LS1, ERC-2013-ADG
Summary "Transcriptional regulation of protein coding genes in eukaryotic cells requires a complex interplay of sequence-specific DNA-binding factors, co-activators, general transcription factors (GTFs), RNA polymerase II and the epigenetic status of target sequences. Nuclear transcription complexes function as large multiprotein assemblies and are often composed of functional modules. The regulated decision-making that exists in cells governing the assembly and the allocation of factors to different transcription complexes to regulate distinct gene expression pathways is not yet understood. To tackle this fundamental question, we will systematically analyse the regulated biogenesis of transcription complexes from their sites of translation in the cytoplasm, through their assembly intermediates and nuclear import, to their site of action in the nucleus. The project will have four main Aims to decipher the biogenesis of transcription complexes:
I) Investigate their co-translation-driven assembly
II) Determine their cytoplasmic intermediates and factors required for their assembly pathways
III) Uncover their nuclear import
IV) Understand at the single molecule level their nuclear assembly, dynamics and action at target genes
To carry out these aims we propose a combination of multidisciplinary and cutting edge approaches, out of which some of them will be high-risk taking, while others will utilize methods routinely run by the group. The project builds on several complementary expertise and knowledge either already existing in the group or that will be implemented during the project. At the end of the proposed project we will obtain novel results extensively describing the different steps of the regulatory mechanisms that control the assembly and the consequent gene regulatory function of transcription complexes. Thus, we anticipate that the results of our research will have a major impact on the field and will lead to a new paradigm for contemporary metazoan transcription."
Summary
"Transcriptional regulation of protein coding genes in eukaryotic cells requires a complex interplay of sequence-specific DNA-binding factors, co-activators, general transcription factors (GTFs), RNA polymerase II and the epigenetic status of target sequences. Nuclear transcription complexes function as large multiprotein assemblies and are often composed of functional modules. The regulated decision-making that exists in cells governing the assembly and the allocation of factors to different transcription complexes to regulate distinct gene expression pathways is not yet understood. To tackle this fundamental question, we will systematically analyse the regulated biogenesis of transcription complexes from their sites of translation in the cytoplasm, through their assembly intermediates and nuclear import, to their site of action in the nucleus. The project will have four main Aims to decipher the biogenesis of transcription complexes:
I) Investigate their co-translation-driven assembly
II) Determine their cytoplasmic intermediates and factors required for their assembly pathways
III) Uncover their nuclear import
IV) Understand at the single molecule level their nuclear assembly, dynamics and action at target genes
To carry out these aims we propose a combination of multidisciplinary and cutting edge approaches, out of which some of them will be high-risk taking, while others will utilize methods routinely run by the group. The project builds on several complementary expertise and knowledge either already existing in the group or that will be implemented during the project. At the end of the proposed project we will obtain novel results extensively describing the different steps of the regulatory mechanisms that control the assembly and the consequent gene regulatory function of transcription complexes. Thus, we anticipate that the results of our research will have a major impact on the field and will lead to a new paradigm for contemporary metazoan transcription."
Max ERC Funding
2 500 000 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
