Project acronym PREDMODSIM
Project Predictive models and simulations in nano- and biomolecular mechanics: a multiscale approach
Researcher (PI) Marino Arroyo
Host Institution (HI) UNIVERSITAT POLITECNICA DE CATALUNYA
Call Details Starting Grant (StG), PE8, ERC-2009-StG
Summary The predictive ability of current simulations of interesting systems in nano- and biomolecular mechanics is questionable due to (1) uncertainties in material behavior of continuum models, (2) severe limitations of atomistic simulations in the computationally accessible length and time scales in relation with the scales of scientific and technological interest, and (3) the limited understanding gained from terabytes of data produced in supercomputing platforms. These difficulties seriously undermine the credibility of computer simulations, as well as their real impact in scientific and technological endeavors. Examples include fundamental challenges in materials science (structure-property relations), molecular biology (sequence-structure-function of proteins), or product engineering (virtual testing for analysis, optimization, control). This proposal addresses three important topics in nano- and biomolecular mechanics, whose full understanding and technological exploitation require predictive models and simulations: (1) Mechanics of carbon nanotubes at engineering scales, (2) Mechanics of fluid membranes in eukaryotic cells and bio-inspired technologies and (3) Local-to-global conformational space exploration and free energy calculations for biomolecules. We follow a multiscale approach, which seeks to incorporate the net effect of the small-scale phenomena described by fundamental models of physics into the coarser (computable) scales at which the system or device operates. In addition to specific impact in these applications, the proposed research is expected to exemplify the potential of multiscale approaches towards predictive and quantitative science and technology, as well as contribute to the credibility and utility of large investments in supercomputing.
Summary
The predictive ability of current simulations of interesting systems in nano- and biomolecular mechanics is questionable due to (1) uncertainties in material behavior of continuum models, (2) severe limitations of atomistic simulations in the computationally accessible length and time scales in relation with the scales of scientific and technological interest, and (3) the limited understanding gained from terabytes of data produced in supercomputing platforms. These difficulties seriously undermine the credibility of computer simulations, as well as their real impact in scientific and technological endeavors. Examples include fundamental challenges in materials science (structure-property relations), molecular biology (sequence-structure-function of proteins), or product engineering (virtual testing for analysis, optimization, control). This proposal addresses three important topics in nano- and biomolecular mechanics, whose full understanding and technological exploitation require predictive models and simulations: (1) Mechanics of carbon nanotubes at engineering scales, (2) Mechanics of fluid membranes in eukaryotic cells and bio-inspired technologies and (3) Local-to-global conformational space exploration and free energy calculations for biomolecules. We follow a multiscale approach, which seeks to incorporate the net effect of the small-scale phenomena described by fundamental models of physics into the coarser (computable) scales at which the system or device operates. In addition to specific impact in these applications, the proposed research is expected to exemplify the potential of multiscale approaches towards predictive and quantitative science and technology, as well as contribute to the credibility and utility of large investments in supercomputing.
Max ERC Funding
1 462 198 €
Duration
Start date: 2009-10-01, End date: 2014-09-30
Project acronym PROGRAM-NANO
Project Programmed Nanostructuration of Organic Materials
Researcher (PI) David Gonzalez Rodriguez
Host Institution (HI) UNIVERSIDAD AUTONOMA DE MADRID
Call Details Starting Grant (StG), PE5, ERC-2011-StG_20101014
Summary “Program-Nano” aims at establishing unconventional and versatile strategies towards organic architectures whose size, composition, internal structure, and function can be rationally predesigned and controlled. In a bio-inspired manner, we will “program” functional molecules with the required information to self-assemble into unique, well-defined nanofibers or nanotubes. We want to focus on two main ambitious objectives for the application of such organic nanostructured materials.
1) The design and preparation of optoelectronic devices, such as plastic solar cells, where nanostructured fibers are integrated within the active layers. The major goal is to determine the influence of the molecular organization and the morphology at the nanoscale on the performance of the device, and to try in this way to set new records in device efficiency.
2) The fabrication of plastic nanoporous materials for the separation, storage or catalytic transformation of (bio)molecules in which the size, the shape ratio, and the internal functionalization of the nanopores can be custom-tailored.
Summary
“Program-Nano” aims at establishing unconventional and versatile strategies towards organic architectures whose size, composition, internal structure, and function can be rationally predesigned and controlled. In a bio-inspired manner, we will “program” functional molecules with the required information to self-assemble into unique, well-defined nanofibers or nanotubes. We want to focus on two main ambitious objectives for the application of such organic nanostructured materials.
1) The design and preparation of optoelectronic devices, such as plastic solar cells, where nanostructured fibers are integrated within the active layers. The major goal is to determine the influence of the molecular organization and the morphology at the nanoscale on the performance of the device, and to try in this way to set new records in device efficiency.
2) The fabrication of plastic nanoporous materials for the separation, storage or catalytic transformation of (bio)molecules in which the size, the shape ratio, and the internal functionalization of the nanopores can be custom-tailored.
Max ERC Funding
1 300 932 €
Duration
Start date: 2011-11-01, End date: 2016-10-31
Project acronym PURPOSE
Project Opening a new route in solid mechanics: Printed protective structures
Researcher (PI) Jose Antonio RODRÍGUEZ-MARTÍNEZ
Host Institution (HI) UNIVERSIDAD CARLOS III DE MADRID
Call Details Starting Grant (StG), PE8, ERC-2017-STG
Summary Dynamic fragmentation of metals is typically addressed within a statistical framework in which material and geometric flaws limit the energy absorption capacity of protective structures. This project is devised to challenge this idea and establish a new framework which incorporates a deterministic component within the fragmentation mechanisms.
In order to check the correctness of this new theory, I will develop a comprehensive experimental, analytical and numerical methodology to address 4 canonical fragmentation problems which respond to distinct geometric and loading conditions which make easily identifiable from a mechanical standpoint. For each canonical problem, I will investigate traditionally-machined and 3D-printed specimens manufactured with 4 different engineering metals widely used in aerospace and civilian-security applications. The goal is to elucidate whether at sufficiently high strain rates there may be a transition in the fragmentation mechanisms from defects–controlled to inertia–controlled. If the new statistical-deterministic framework is proven to be valid, defects may not play the major role in the fragmentation at high strain rates. This would bring down the entry barriers that the 3D-printing technology has found in energy absorption applications, thus reducing production transportation and repairing, energetic and economic costs of protective structures without impairing their energy absorption capacity.
It is anticipated that leading this cutting-edge research project will enable me to establish my own research team and help me to achieve career independence in the field of dynamic behaviour of ductile solids.
Summary
Dynamic fragmentation of metals is typically addressed within a statistical framework in which material and geometric flaws limit the energy absorption capacity of protective structures. This project is devised to challenge this idea and establish a new framework which incorporates a deterministic component within the fragmentation mechanisms.
In order to check the correctness of this new theory, I will develop a comprehensive experimental, analytical and numerical methodology to address 4 canonical fragmentation problems which respond to distinct geometric and loading conditions which make easily identifiable from a mechanical standpoint. For each canonical problem, I will investigate traditionally-machined and 3D-printed specimens manufactured with 4 different engineering metals widely used in aerospace and civilian-security applications. The goal is to elucidate whether at sufficiently high strain rates there may be a transition in the fragmentation mechanisms from defects–controlled to inertia–controlled. If the new statistical-deterministic framework is proven to be valid, defects may not play the major role in the fragmentation at high strain rates. This would bring down the entry barriers that the 3D-printing technology has found in energy absorption applications, thus reducing production transportation and repairing, energetic and economic costs of protective structures without impairing their energy absorption capacity.
It is anticipated that leading this cutting-edge research project will enable me to establish my own research team and help me to achieve career independence in the field of dynamic behaviour of ductile solids.
Max ERC Funding
1 497 507 €
Duration
Start date: 2018-03-01, End date: 2023-02-28
Project acronym RACCOON
Project A Rigorous Approach to Consistency in Cloud Databases
Researcher (PI) Alexey Gotsman
Host Institution (HI) FUNDACION IMDEA SOFTWARE
Call Details Starting Grant (StG), PE6, ERC-2016-STG
Summary Modern Internet services store data in novel cloud databases, which partition and replicate the data across a large number of machines and a wide geographical span. To achieve high availability and scalability, cloud databases need to maximise the parallelism of data processing. Unfortunately, this leads them to weaken the guarantees they provide about data consistency to applications. The resulting programming models are very challenging to use correctly, and we currently do not have advanced methods and tools that would help programmers in this task.
The goal of the project is to develop a synergy of novel reasoning methods, static analysis tools and database implementation techniques that maximally exploit parallelism inside cloud databases, while enabling application programmers to ensure correctness. We intend to achieve this by first developing methods for reasoning formally about how weakening the consistency guarantees provided by cloud databases affects application correctness and the parallelism allowed inside the databases. This will build on techniques from the areas of programming languages and software verification. The resulting theory will then serve as a basis for practical implementation techniques and tools that harness database parallelism, but only to the extent such that its side effects do not compromise application correctness.
The proposed project is high-risk, because it aims not only to develop a rigorous theory of consistency in cloud databases, but also to apply it to practical systems design. The project is also high-gain, since it will push the envelope in availability, scalability and cost-effectiveness of cloud databases.
Summary
Modern Internet services store data in novel cloud databases, which partition and replicate the data across a large number of machines and a wide geographical span. To achieve high availability and scalability, cloud databases need to maximise the parallelism of data processing. Unfortunately, this leads them to weaken the guarantees they provide about data consistency to applications. The resulting programming models are very challenging to use correctly, and we currently do not have advanced methods and tools that would help programmers in this task.
The goal of the project is to develop a synergy of novel reasoning methods, static analysis tools and database implementation techniques that maximally exploit parallelism inside cloud databases, while enabling application programmers to ensure correctness. We intend to achieve this by first developing methods for reasoning formally about how weakening the consistency guarantees provided by cloud databases affects application correctness and the parallelism allowed inside the databases. This will build on techniques from the areas of programming languages and software verification. The resulting theory will then serve as a basis for practical implementation techniques and tools that harness database parallelism, but only to the extent such that its side effects do not compromise application correctness.
The proposed project is high-risk, because it aims not only to develop a rigorous theory of consistency in cloud databases, but also to apply it to practical systems design. The project is also high-gain, since it will push the envelope in availability, scalability and cost-effectiveness of cloud databases.
Max ERC Funding
1 498 312 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym RASPA
Project Towards more efficient materials for technological processes
Researcher (PI) Sofia Calero Diaz
Host Institution (HI) UNIVERSIDAD PABLO DE OLAVIDE
Call Details Starting Grant (StG), PE8, ERC-2011-StG_20101014
Summary With the increasing need for efficient, energy-saving, and environmentally friendly procedures, adsorbents with tailored structures and tunable surface properties have to be found. To make an informed choice of material for a given application, one must first have knowledge of its adsorption behaviour as a function of molecular composition and morphology. My aim is to provide new insights for material design with a computational investigation of adsorption and diffusion processes in porous materials. As adsorbents I will focus on zeolites because of their high stability and on MOFs because of their structural diversity and versatility. As adsorbates I am interested on chiral molecules such as ibuprofen or limonene (separation of chiral enantiomers), volatile organic compounds –VOCs- (control of VOCs emissions from industrial processes), water, alcohols (solvent dehydration), carbon dioxide and methane (production of cheap and clean fuel from natural gas).
The central focus of this research is that computer simulations can be used not only as a screening tool for known structures, but they can also provide structural design guides even before experimental synthesis. My approach is to perform a classical simulation study to identify the effect of the geometry and the chemical composition of the material on storage/release of molecules and on separation of mixtures. The fundamental information that I am planning to obtain from this study will provide the underlying knowledge from a molecular point of view that may guide to the development of more efficient processes, to fine-tune materials for a particular application and also to steer the experimental effort in successful directions.
Summary
With the increasing need for efficient, energy-saving, and environmentally friendly procedures, adsorbents with tailored structures and tunable surface properties have to be found. To make an informed choice of material for a given application, one must first have knowledge of its adsorption behaviour as a function of molecular composition and morphology. My aim is to provide new insights for material design with a computational investigation of adsorption and diffusion processes in porous materials. As adsorbents I will focus on zeolites because of their high stability and on MOFs because of their structural diversity and versatility. As adsorbates I am interested on chiral molecules such as ibuprofen or limonene (separation of chiral enantiomers), volatile organic compounds –VOCs- (control of VOCs emissions from industrial processes), water, alcohols (solvent dehydration), carbon dioxide and methane (production of cheap and clean fuel from natural gas).
The central focus of this research is that computer simulations can be used not only as a screening tool for known structures, but they can also provide structural design guides even before experimental synthesis. My approach is to perform a classical simulation study to identify the effect of the geometry and the chemical composition of the material on storage/release of molecules and on separation of mixtures. The fundamental information that I am planning to obtain from this study will provide the underlying knowledge from a molecular point of view that may guide to the development of more efficient processes, to fine-tune materials for a particular application and also to steer the experimental effort in successful directions.
Max ERC Funding
1 369 080 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym REFORMED
Project Reforming Schools Globally: A Multi-Scalar Analysis of Autonomy and Accountability Policies in the Education Sector
Researcher (PI) Antoni Verger Planells
Host Institution (HI) UNIVERSITAT AUTONOMA DE BARCELONA
Call Details Starting Grant (StG), SH2, ERC-2015-STG
Summary Most countries in the world are facing reform pressures to make their education systems more effective and responsive to the new challenges generated by the global economy. In this scenario, managerial policy ideas such as school autonomy and accountability, which aim to modernize public education and strengthen its performance, are spreading broadly. To date, a wide range of countries with different administrative traditions and levels of development have adopted school autonomy with accountability (SAWA) policies, whilst the most active international organizations in the education sector, like the OECD, are strongly promoting them globally.
Constituting SAWA as a global model of education reform generates two main questions. First, why and how are SAWA policies disseminating globally, and to what extent does this reform model generate international policy convergence in education? Secondly, how and under what particular contextual and institutional circumstances do SAWA policies work and for whom? The fact that existing scholarly research has achieved inconclusive and mixed findings concerning the SAWA effects on learning outcomes and equity makes this second question especially relevant.
To address these gaps in existing literature, REFORMED develops a comprehensive research approach that scrutinizes the different, but mutually constitutive stages of global education policy, from the inception in global agendas stage to their operationalization and effects in multiple contexts. Specifically, the project analyzes how and why SAWA policies are being adopted and re-formulated by policy actors operating at different scales (from international bureaucrats to teachers), and inquires into the institutional frameworks and policy enactment processes that explain the different effects of SAWA at the school level. A robust and multi-scalar methodological strategy that combines quantitative and qualitative methods will contribute to advancing such an innovative approach.
Summary
Most countries in the world are facing reform pressures to make their education systems more effective and responsive to the new challenges generated by the global economy. In this scenario, managerial policy ideas such as school autonomy and accountability, which aim to modernize public education and strengthen its performance, are spreading broadly. To date, a wide range of countries with different administrative traditions and levels of development have adopted school autonomy with accountability (SAWA) policies, whilst the most active international organizations in the education sector, like the OECD, are strongly promoting them globally.
Constituting SAWA as a global model of education reform generates two main questions. First, why and how are SAWA policies disseminating globally, and to what extent does this reform model generate international policy convergence in education? Secondly, how and under what particular contextual and institutional circumstances do SAWA policies work and for whom? The fact that existing scholarly research has achieved inconclusive and mixed findings concerning the SAWA effects on learning outcomes and equity makes this second question especially relevant.
To address these gaps in existing literature, REFORMED develops a comprehensive research approach that scrutinizes the different, but mutually constitutive stages of global education policy, from the inception in global agendas stage to their operationalization and effects in multiple contexts. Specifically, the project analyzes how and why SAWA policies are being adopted and re-formulated by policy actors operating at different scales (from international bureaucrats to teachers), and inquires into the institutional frameworks and policy enactment processes that explain the different effects of SAWA at the school level. A robust and multi-scalar methodological strategy that combines quantitative and qualitative methods will contribute to advancing such an innovative approach.
Max ERC Funding
1 002 307 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym RESTRICTION
Project Restriction of the Fourier transform with applications to the Schrödinger and wave equations
Researcher (PI) Keith Mckenzie Rogers
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Starting Grant (StG), PE1, ERC-2011-StG_20101014
Summary In 1967, Stein proved that the Fourier transform of functions in L^p could be meaningfully restricted to the sphere for certain p>1. The restriction conjecture, which asserts the maximal range of such p, was solved by Fefferman in two dimensions, but the conjecture remains open in higher dimensions. Strichartz considered the same question but with the sphere replaced by the paraboloid or the cone, and a great deal of progress has been made in the last two decades by Bourgain, Wolff and Tao, among others. Due to the fact that the adjoint operators of the restriction operators to the paraboloid and cone correspond to the Schrödinger and wave evolution operators, respectively, this work has been hugely influential. The main goal of this proposal is to improve the state of the art for the mixed norm analogues of these conjectures.
Summary
In 1967, Stein proved that the Fourier transform of functions in L^p could be meaningfully restricted to the sphere for certain p>1. The restriction conjecture, which asserts the maximal range of such p, was solved by Fefferman in two dimensions, but the conjecture remains open in higher dimensions. Strichartz considered the same question but with the sphere replaced by the paraboloid or the cone, and a great deal of progress has been made in the last two decades by Bourgain, Wolff and Tao, among others. Due to the fact that the adjoint operators of the restriction operators to the paraboloid and cone correspond to the Schrödinger and wave evolution operators, respectively, this work has been hugely influential. The main goal of this proposal is to improve the state of the art for the mixed norm analogues of these conjectures.
Max ERC Funding
950 000 €
Duration
Start date: 2011-09-01, End date: 2017-08-31
Project acronym RIVERS
Project Water/human rights beyond the human?Indigenous water ontologies, plurilegal encounters and interlegal translation
Researcher (PI) Lieselotte VIAENE
Host Institution (HI) UNIVERSIDAD CARLOS III DE MADRID
Call Details Starting Grant (StG), SH2, ERC-2018-STG
Summary RIVERS’s main challenge is to produce ground-breaking knowledge, from an empirical, interdisciplinary and dialoguing perspective, about the contentions and challenges intrinsic to reconceptualising human rights with different ways of understanding and relating to water. Worldwide, indigenous peoples are mobilising against the neoliberalisation of nature, demonstrating radically different ways of knowing, being and living. At the same time, in 2010 the UN acknowledged water as a human right, while in 2017 New Zealand, India and Colombia established ground-breaking legal precedents by granting rivers human rights. RIVERS’s overarching research question is: To what extent can international human rights law come to grips with plurilegal water realities? This project engages with one of the most pressing questions of this century: the relationship between humans and nature. RIVERS tackles two intertwined core objectives: 1) analysing different ways of knowing and relating to water and life among indigenous peoples and their understanding of its (potential) violation by extractive projects; 2) discussing the contributions, challenges and pitfalls of interlegal translation of differing water natures in plurilegal encounters at domestic and international levels. RIVERS will develop a multi-sited analysis and empirical case-studies in three contexts: Colombia, Nepal and the UN human rights protection system. Through the lens of legal pluralism, this will foreground competing political and legal water realities that interrogate dominant understandings of the modern world. RIVERS will address two interrelated research challenges: 1) indigenous visions/practices: beyond water as a natural resource and human right; 2) the UN human rights system: towards counter-hegemonic water knowledge production. This project will pioneer new ways of thinking about water beyond the modern divides of nature/culture, providing clues about future paths towards reconceptualising human rights.
Summary
RIVERS’s main challenge is to produce ground-breaking knowledge, from an empirical, interdisciplinary and dialoguing perspective, about the contentions and challenges intrinsic to reconceptualising human rights with different ways of understanding and relating to water. Worldwide, indigenous peoples are mobilising against the neoliberalisation of nature, demonstrating radically different ways of knowing, being and living. At the same time, in 2010 the UN acknowledged water as a human right, while in 2017 New Zealand, India and Colombia established ground-breaking legal precedents by granting rivers human rights. RIVERS’s overarching research question is: To what extent can international human rights law come to grips with plurilegal water realities? This project engages with one of the most pressing questions of this century: the relationship between humans and nature. RIVERS tackles two intertwined core objectives: 1) analysing different ways of knowing and relating to water and life among indigenous peoples and their understanding of its (potential) violation by extractive projects; 2) discussing the contributions, challenges and pitfalls of interlegal translation of differing water natures in plurilegal encounters at domestic and international levels. RIVERS will develop a multi-sited analysis and empirical case-studies in three contexts: Colombia, Nepal and the UN human rights protection system. Through the lens of legal pluralism, this will foreground competing political and legal water realities that interrogate dominant understandings of the modern world. RIVERS will address two interrelated research challenges: 1) indigenous visions/practices: beyond water as a natural resource and human right; 2) the UN human rights system: towards counter-hegemonic water knowledge production. This project will pioneer new ways of thinking about water beyond the modern divides of nature/culture, providing clues about future paths towards reconceptualising human rights.
Max ERC Funding
1 498 446 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym SeeSuper
Project Probing nanoscale and femtosecond fluctuations in high temperature superconductors
Researcher (PI) Simon Wall
Host Institution (HI) FUNDACIO INSTITUT DE CIENCIES FOTONIQUES
Call Details Starting Grant (StG), PE3, ERC-2017-STG
Summary One of the major outstanding challenges in condensed matter physics is the origin of high temperature superconductivity. Low temperature BCS superconductivity is mediated by the electron-phonon interaction, but this interaction is believed to be too weak to explain high temperature superconductivity. Instead electron interactions are considered responsible, but experimental proof has been difficult to obtain. Despite over thirty years of research, the mechanism responsible for generating the superconducting state still remains unknown.
SeeSuper aims to break this deadlock by applying new experimental techniques to study the superconducting state. Our strategy is to probe high temperature superconductors through their nanoscale and femtosecond fluctuations. We will focus on three key parameters in superconductors: phonons, spins and nanoscale phase separation, with the aim of revealing the coupling mechanism.
Our approach combines transient optical spectroscopy and time-resolved diffuse X-ray scattering to measure the lattice response to large amplitude coherent vibrations, time-resolved non-linear optical spectroscopy to directly probe spin dynamics, and resonant soft X-ray holography to image dynamics on the nanoscale.
We will use these cutting edge techniques to prove our hypothesis, that lattice anharmonicity is the key missing ingredient to explain the origins of high temperature superconductivity. If demonstrated, the impact of such a result will lead to a step-change in our understanding of how superconductivity at high temperature occurs, help guide the search for materials with higher transition temperatures, and influence how we view and understand a much broader class of materials. Furthermore, the experimental techniques that we will develop can be applied to understand a range of materials and will, therefore, have an impact also on the broader field of condensed matter physics.
Summary
One of the major outstanding challenges in condensed matter physics is the origin of high temperature superconductivity. Low temperature BCS superconductivity is mediated by the electron-phonon interaction, but this interaction is believed to be too weak to explain high temperature superconductivity. Instead electron interactions are considered responsible, but experimental proof has been difficult to obtain. Despite over thirty years of research, the mechanism responsible for generating the superconducting state still remains unknown.
SeeSuper aims to break this deadlock by applying new experimental techniques to study the superconducting state. Our strategy is to probe high temperature superconductors through their nanoscale and femtosecond fluctuations. We will focus on three key parameters in superconductors: phonons, spins and nanoscale phase separation, with the aim of revealing the coupling mechanism.
Our approach combines transient optical spectroscopy and time-resolved diffuse X-ray scattering to measure the lattice response to large amplitude coherent vibrations, time-resolved non-linear optical spectroscopy to directly probe spin dynamics, and resonant soft X-ray holography to image dynamics on the nanoscale.
We will use these cutting edge techniques to prove our hypothesis, that lattice anharmonicity is the key missing ingredient to explain the origins of high temperature superconductivity. If demonstrated, the impact of such a result will lead to a step-change in our understanding of how superconductivity at high temperature occurs, help guide the search for materials with higher transition temperatures, and influence how we view and understand a much broader class of materials. Furthermore, the experimental techniques that we will develop can be applied to understand a range of materials and will, therefore, have an impact also on the broader field of condensed matter physics.
Max ERC Funding
1 789 165 €
Duration
Start date: 2017-11-01, End date: 2022-10-31
Project acronym SM-DNA-REPAIR
Project New single-molecule techniques and their application in the study of DNA break repair
Researcher (PI) Fernando Moreno Herrero
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Call Details Starting Grant (StG), PE3, ERC-2007-StG
Summary Unrepaired DNA breaks can lead to genomic instability or cell death. They occur frequently during normal cellular metabolism and are caused, for example, by the collapse or stalling of the replication fork in response to DNA damage. Proper DNA-end processing and handling are essential for the survival of the cell and prevention of carcinogenesis. Cells possess robust mechanisms to repair DNA breaks. One such DNA repair mechanism is homologous recombination where the sister chromatid is used as a template for the faithful repair of the DNA break. In Bacteria, this pathway is initiated when a DNA end is processed to a 3-ssDNA overhang terminated at a recombination hotspot (Chi) sequence. This is a substrate for formation of a RecA nucleoprotein filament that catalyses strand exchange to promote repair. Recent data implicate the AddAB helicase-nuclease and the SMC (Structural Maintenance of Chromosomes) complex in the DNA break processing mechanism of the model organism Bacillus subtilis. Interaction between these machines provides a molecular link between DNA dynamics and the initiation of DNA break processing that may co-ordinate replication fork collapse and DNA repair. Single-molecule manipulation and imaging techniques offer huge potential to investigate DNA break repair reactions in completely new ways, providing information that is inaccessible to conventional ensemble experiments. The aim of this project is two-fold: firstly, to develop novel biophysical instruments for fast Atomic Force Microscopy imaging in liquid and a combined Optical and Magnetic Tweezers setup; and secondly, to monitor and characterize the real-time dynamics of these DNA-repair processes using these new and complementary biophysical approaches. Single-molecule investigation will be supported by statistical analysis of the data and conventional bulk biochemical techniques.
Summary
Unrepaired DNA breaks can lead to genomic instability or cell death. They occur frequently during normal cellular metabolism and are caused, for example, by the collapse or stalling of the replication fork in response to DNA damage. Proper DNA-end processing and handling are essential for the survival of the cell and prevention of carcinogenesis. Cells possess robust mechanisms to repair DNA breaks. One such DNA repair mechanism is homologous recombination where the sister chromatid is used as a template for the faithful repair of the DNA break. In Bacteria, this pathway is initiated when a DNA end is processed to a 3-ssDNA overhang terminated at a recombination hotspot (Chi) sequence. This is a substrate for formation of a RecA nucleoprotein filament that catalyses strand exchange to promote repair. Recent data implicate the AddAB helicase-nuclease and the SMC (Structural Maintenance of Chromosomes) complex in the DNA break processing mechanism of the model organism Bacillus subtilis. Interaction between these machines provides a molecular link between DNA dynamics and the initiation of DNA break processing that may co-ordinate replication fork collapse and DNA repair. Single-molecule manipulation and imaging techniques offer huge potential to investigate DNA break repair reactions in completely new ways, providing information that is inaccessible to conventional ensemble experiments. The aim of this project is two-fold: firstly, to develop novel biophysical instruments for fast Atomic Force Microscopy imaging in liquid and a combined Optical and Magnetic Tweezers setup; and secondly, to monitor and characterize the real-time dynamics of these DNA-repair processes using these new and complementary biophysical approaches. Single-molecule investigation will be supported by statistical analysis of the data and conventional bulk biochemical techniques.
Max ERC Funding
1 624 230 €
Duration
Start date: 2008-08-01, End date: 2013-07-31