Project acronym AlgoFinance
Project Algorithmic Finance: Inquiring into the Reshaping of Financial Markets
Researcher (PI) Christian BORCH
Host Institution (HI) COPENHAGEN BUSINESS SCHOOL
Call Details Consolidator Grant (CoG), SH3, ERC-2016-COG
Summary Present-day financial markets are turning algorithmic, as market orders are increasingly being executed by fully automated computer algorithms, without any direct human intervention. Although algorithmic finance seems to fundamentally reshape the central dynamics in financial markets, and even though it prompts core sociological questions, it has not yet received any systematic attention. In a pioneering contribution to economic sociology and social studies of finance, ALGOFINANCE aims to understand how and with what consequences the turn to algorithms is changing financial markets. The overall concept and central contributions of ALGOFINANCE are the following: (1) on an intra-firm level, the project examines how the shift to algorithmic finance reshapes the ways in which trading firms operate, and does so by systematically and empirically investigating the reconfiguration of organizational structures and employee subjectivity; (2) on an inter-algorithmic level, it offers a ground-breaking methodology (agent-based modelling informed by qualitative data) to grasp how trading algorithms interact with one another in a fully digital space; and (3) on the level of market sociality, it proposes a novel theorization of how intra-firm and inter-algorithmic dynamics can be conceived of as introducing a particular form of sociality that is characteristic to algorithmic finance: a form of sociality-as-association heuristically analyzed as imitation. None of these three levels have received systematic attention in the state-of-the-art literature. Addressing them will significantly advance the understanding of present-day algorithmic finance in economic sociology. By contributing novel empirical, methodological, and theoretical understandings of the functioning and consequences of algorithms, ALGOFINANCE will pave the way for other research into digital sociology and the broader algorithmization of society.
Summary
Present-day financial markets are turning algorithmic, as market orders are increasingly being executed by fully automated computer algorithms, without any direct human intervention. Although algorithmic finance seems to fundamentally reshape the central dynamics in financial markets, and even though it prompts core sociological questions, it has not yet received any systematic attention. In a pioneering contribution to economic sociology and social studies of finance, ALGOFINANCE aims to understand how and with what consequences the turn to algorithms is changing financial markets. The overall concept and central contributions of ALGOFINANCE are the following: (1) on an intra-firm level, the project examines how the shift to algorithmic finance reshapes the ways in which trading firms operate, and does so by systematically and empirically investigating the reconfiguration of organizational structures and employee subjectivity; (2) on an inter-algorithmic level, it offers a ground-breaking methodology (agent-based modelling informed by qualitative data) to grasp how trading algorithms interact with one another in a fully digital space; and (3) on the level of market sociality, it proposes a novel theorization of how intra-firm and inter-algorithmic dynamics can be conceived of as introducing a particular form of sociality that is characteristic to algorithmic finance: a form of sociality-as-association heuristically analyzed as imitation. None of these three levels have received systematic attention in the state-of-the-art literature. Addressing them will significantly advance the understanding of present-day algorithmic finance in economic sociology. By contributing novel empirical, methodological, and theoretical understandings of the functioning and consequences of algorithms, ALGOFINANCE will pave the way for other research into digital sociology and the broader algorithmization of society.
Max ERC Funding
1 590 036 €
Duration
Start date: 2017-05-01, End date: 2021-04-30
Project acronym ALLQUANTUM
Project All-solid-state quantum electrodynamics in photonic crystals
Researcher (PI) Peter Lodahl
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), PE2, ERC-2010-StG_20091028
Summary In quantum electrodynamics a range of fundamental processes are driven by omnipresent vacuum fluctuations. Photonic crystals can control vacuum fluctuations and thereby the fundamental interaction between light and matter. We will conduct experiments on quantum dots in photonic crystals and observe novel quantum electrodynamics effects including fractional decay and the modified Lamb shift. Furthermore, photonic crystals will be explored for shielding sensitive quantum-superposition states against decoherence.
Defects in photonic crystals allow novel functionalities enabling nanocavities and waveguides. We will use the tight confinement of light in a nanocavity to entangle a quantum dot and a photon, and explore the scalability. Controlled ways of generating scalable and robust quantum entanglement is the essential missing link limiting quantum communication and quantum computing. A single quantum dot coupled to a slowly propagating mode in a photonic crystal waveguide will be used to induce large nonlinearities at the few-photon level.
Finally we will explore a novel route to enhanced light-matter interaction employing controlled disorder in photonic crystals. In disordered media multiple scattering of light takes place and can lead to the formation of Anderson-localized modes. We will explore cavity quantum electrodynamics in Anderson-localized random cavities considering disorder a resource and not a nuisance, which is the traditional view.
The main focus of the project will be on optical experiments, but fabrication of photonic crystals and detailed theory will be carried out as well. Several of the proposed experiments will constitute milestones in quantum optics and may pave the way for all-solid-state quantum communication with quantum dots in photonic crystals.
Summary
In quantum electrodynamics a range of fundamental processes are driven by omnipresent vacuum fluctuations. Photonic crystals can control vacuum fluctuations and thereby the fundamental interaction between light and matter. We will conduct experiments on quantum dots in photonic crystals and observe novel quantum electrodynamics effects including fractional decay and the modified Lamb shift. Furthermore, photonic crystals will be explored for shielding sensitive quantum-superposition states against decoherence.
Defects in photonic crystals allow novel functionalities enabling nanocavities and waveguides. We will use the tight confinement of light in a nanocavity to entangle a quantum dot and a photon, and explore the scalability. Controlled ways of generating scalable and robust quantum entanglement is the essential missing link limiting quantum communication and quantum computing. A single quantum dot coupled to a slowly propagating mode in a photonic crystal waveguide will be used to induce large nonlinearities at the few-photon level.
Finally we will explore a novel route to enhanced light-matter interaction employing controlled disorder in photonic crystals. In disordered media multiple scattering of light takes place and can lead to the formation of Anderson-localized modes. We will explore cavity quantum electrodynamics in Anderson-localized random cavities considering disorder a resource and not a nuisance, which is the traditional view.
The main focus of the project will be on optical experiments, but fabrication of photonic crystals and detailed theory will be carried out as well. Several of the proposed experiments will constitute milestones in quantum optics and may pave the way for all-solid-state quantum communication with quantum dots in photonic crystals.
Max ERC Funding
1 199 648 €
Duration
Start date: 2010-12-01, End date: 2015-11-30
Project acronym AMPLITUDES
Project Manifesting the Simplicity of Scattering Amplitudes
Researcher (PI) Jacob BOURJAILY
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), PE2, ERC-2017-STG
Summary I propose a program of research that may forever change the way that we understand and use quantum field theory to make predictions for experiment. This will be achieved through the advancement of new, constructive frameworks to determine and represent scattering amplitudes in perturbation theory in terms that depend only on observable quantities, make manifest (all) the symmetries of the theory, and which can be efficiently evaluated while minimally spoiling the underlying simplicity of predictions. My research has already led to the discovery and development of several approaches of this kind.
This proposal describes the specific steps required to extend these ideas to more general theories and to higher orders of perturbation theory. Specifically, the plan of research I propose consists of three concrete goals: to fully characterize the discontinuities of loop amplitudes (`on-shell functions') for a broad class of theories; to develop powerful new representations of loop amplitude {\it integrands}, making manifest as much simplicity as possible; and to develop new techniques for loop amplitude {integration} that are compatible with and preserve the symmetries of observable quantities.
Progress toward any one of these objectives would have important theoretical implications and valuable practical applications. In combination, this proposal has the potential to significantly advance the state of the art for both our theoretical understanding and our computational reach for making predictions for experiment.
To achieve these goals, I will pursue a data-driven, `phenomenological' approach—involving the construction of new computational tools, developed in pursuit of concrete computational targets. For this work, my suitability and expertise is amply demonstrated by my research. I have not only played a key role in many of the most important theoretical developments in the past decade, but I have personally built the most powerful computational tools for their
Summary
I propose a program of research that may forever change the way that we understand and use quantum field theory to make predictions for experiment. This will be achieved through the advancement of new, constructive frameworks to determine and represent scattering amplitudes in perturbation theory in terms that depend only on observable quantities, make manifest (all) the symmetries of the theory, and which can be efficiently evaluated while minimally spoiling the underlying simplicity of predictions. My research has already led to the discovery and development of several approaches of this kind.
This proposal describes the specific steps required to extend these ideas to more general theories and to higher orders of perturbation theory. Specifically, the plan of research I propose consists of three concrete goals: to fully characterize the discontinuities of loop amplitudes (`on-shell functions') for a broad class of theories; to develop powerful new representations of loop amplitude {\it integrands}, making manifest as much simplicity as possible; and to develop new techniques for loop amplitude {integration} that are compatible with and preserve the symmetries of observable quantities.
Progress toward any one of these objectives would have important theoretical implications and valuable practical applications. In combination, this proposal has the potential to significantly advance the state of the art for both our theoretical understanding and our computational reach for making predictions for experiment.
To achieve these goals, I will pursue a data-driven, `phenomenological' approach—involving the construction of new computational tools, developed in pursuit of concrete computational targets. For this work, my suitability and expertise is amply demonstrated by my research. I have not only played a key role in many of the most important theoretical developments in the past decade, but I have personally built the most powerful computational tools for their
Max ERC Funding
1 499 695 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym CRIMTANG
Project Criminal Entanglements.A new ethnographic approach to transnational organised crime.
Researcher (PI) Henrik VIGH
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Consolidator Grant (CoG), SH3, ERC-2016-COG
Summary Linked to terrorism, moral breakdown, and societal decay, Transnational Organised Crime (TOC) has come to embody current global anxieties as a figure of fear and cause of disquiet. Yet despite its central position on the social and political radar, our knowledge of it remains limited and fragmentary. Quantitative analyses may have identified the scale of the problem, but its underlying socio-cultural logic and practices remain under-researched and largely obscure. TOC is on the rise, and we need better insights into how it develops and expands, who engages in it and why, and how it is linked to and embedded in social networks that straddle countries and contexts.
CRIMTANG proposes a unique approach to the study of the social infrastructure of contemporary TOC. It develops a research strategy that is ethnographic and transnational in design and so attuned to the human flows and formations of TOC. The project comprises a trans-disciplinary research team of anthropologists, criminologists and political scientists, and builds on their prior experience of the people, regions and languages under study. It explores the illegal and overlapping flows of migrants and drugs from North-West Africa into Europe, following a key trafficking trajectory stretching from Tangiers to Barcelona, Paris and beyond.
In so doing, CRIMTANG sheds new light on the actual empirical processes in operation at different points along this trafficking route, whilst simultaneously developing new theoretical and methodological apparatuses for apprehending TOC that can be exported and applied in other regions and contexts. It reimagines the idea of social entanglement and proposes new transnational and collective fieldwork strategies. Finally, it will advance and consolidate the European research environment on TOC by creating a research hub for transnational ethnographic criminology at the University of Copenhagen.
Summary
Linked to terrorism, moral breakdown, and societal decay, Transnational Organised Crime (TOC) has come to embody current global anxieties as a figure of fear and cause of disquiet. Yet despite its central position on the social and political radar, our knowledge of it remains limited and fragmentary. Quantitative analyses may have identified the scale of the problem, but its underlying socio-cultural logic and practices remain under-researched and largely obscure. TOC is on the rise, and we need better insights into how it develops and expands, who engages in it and why, and how it is linked to and embedded in social networks that straddle countries and contexts.
CRIMTANG proposes a unique approach to the study of the social infrastructure of contemporary TOC. It develops a research strategy that is ethnographic and transnational in design and so attuned to the human flows and formations of TOC. The project comprises a trans-disciplinary research team of anthropologists, criminologists and political scientists, and builds on their prior experience of the people, regions and languages under study. It explores the illegal and overlapping flows of migrants and drugs from North-West Africa into Europe, following a key trafficking trajectory stretching from Tangiers to Barcelona, Paris and beyond.
In so doing, CRIMTANG sheds new light on the actual empirical processes in operation at different points along this trafficking route, whilst simultaneously developing new theoretical and methodological apparatuses for apprehending TOC that can be exported and applied in other regions and contexts. It reimagines the idea of social entanglement and proposes new transnational and collective fieldwork strategies. Finally, it will advance and consolidate the European research environment on TOC by creating a research hub for transnational ethnographic criminology at the University of Copenhagen.
Max ERC Funding
1 999 909 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym DropletControl
Project Controlling the orientation of molecules inside liquid helium nanodroplets
Researcher (PI) Henrik Stapelfeldt
Host Institution (HI) AARHUS UNIVERSITET
Call Details Advanced Grant (AdG), PE2, ERC-2012-ADG_20120216
Summary In this project I will develop and exploit experimental methods, based on short and intense laser pulses, to control the spatial orientation of molecules dissolved in liquid helium nanodroplets. This idea is, so far, completely unexplored but it has the potential to open a multitude of new opportunities in physics and chemistry. The main objectives are:
1) Complete control and real time monitoring of molecular rotation inside liquid helium droplets, exploring superfluidity of the droplets, the possible formation of quantum vortices, and rotational dephasing due to interaction of the dissolved molecules with the He solvent.
2) Ultrafast imaging of molecules undergoing chemical reaction dynamics inside liquid helium droplets, exploring rapid energy dissipation from reacting molecules to the helium solvent, transition between mirror forms of chiral molecules, strong laser field processes in He-solvated molecules, and structure determination of non crystalizable proteins by electron or x-ray diffraction.
I will achieve the objectives by combining liquid helium droplet technology, ultrafast laser pulse methods and advanced electron and ion imaging detection. The experiments will both rely on existing apparatus in my laboratories and on new vacuum and laser equipment to be set up during the project.
The ability to control how molecules are turned in space is of fundamental importance because interactions of molecules with other molecules, atoms or radiation depend on their spatial orientation. For isolated molecules in the gas phase laser based methods, developed over the past 12 years, now enable very refined and precise control over the spatial orientation of molecules. By contrast, orientational control of molecules in solution has not been demonstrated despite the potential of being able to do so is enormous, notably because most chemistry occurs in a solvent rather than in a gas of isolated molecules.
Summary
In this project I will develop and exploit experimental methods, based on short and intense laser pulses, to control the spatial orientation of molecules dissolved in liquid helium nanodroplets. This idea is, so far, completely unexplored but it has the potential to open a multitude of new opportunities in physics and chemistry. The main objectives are:
1) Complete control and real time monitoring of molecular rotation inside liquid helium droplets, exploring superfluidity of the droplets, the possible formation of quantum vortices, and rotational dephasing due to interaction of the dissolved molecules with the He solvent.
2) Ultrafast imaging of molecules undergoing chemical reaction dynamics inside liquid helium droplets, exploring rapid energy dissipation from reacting molecules to the helium solvent, transition between mirror forms of chiral molecules, strong laser field processes in He-solvated molecules, and structure determination of non crystalizable proteins by electron or x-ray diffraction.
I will achieve the objectives by combining liquid helium droplet technology, ultrafast laser pulse methods and advanced electron and ion imaging detection. The experiments will both rely on existing apparatus in my laboratories and on new vacuum and laser equipment to be set up during the project.
The ability to control how molecules are turned in space is of fundamental importance because interactions of molecules with other molecules, atoms or radiation depend on their spatial orientation. For isolated molecules in the gas phase laser based methods, developed over the past 12 years, now enable very refined and precise control over the spatial orientation of molecules. By contrast, orientational control of molecules in solution has not been demonstrated despite the potential of being able to do so is enormous, notably because most chemistry occurs in a solvent rather than in a gas of isolated molecules.
Max ERC Funding
2 409 773 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym DTSSCP
Project Determinants of mammalian transcription start site selection and core promoter usage
Researcher (PI) Albin Sandelin
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), LS2, ERC-2007-StG
Summary Understanding the mechanisms underlying the initiation and regulation of transcription remains one of the most fundamental questions in biology. Much of what we know about the transcription process was inferred from experiments on a handful of genes. As these experiments are not realistically scalable, corresponding computational methods building on these findings have emerged; however, these are not accurate enough for annotation of genomes. The limitations reflect that we have no accurate universal model describing transcription initiation; to a large extent, our understanding is based on case stories. Recently, high-throughput methods have been developed to chart the TSS landscape with nucleotide resolution. Using these data, I have dissected promoters at nucleotide level and found patterns that explain the transcription initiation rate for individual nucleotides. The objective for this work is to extend this to the first universal model for how cells select core promoters and associated TSSs. This will have two counterparts: i)prediction of TSSs from DNA sequence given a region of accessible DNA, and ii)prediction of DNA accessibility based on DNA sequences and dynamic epigenetic factors. Such a model will be a corner stone of future experimental and computational transcriptome and gene regulation studies.
Summary
Understanding the mechanisms underlying the initiation and regulation of transcription remains one of the most fundamental questions in biology. Much of what we know about the transcription process was inferred from experiments on a handful of genes. As these experiments are not realistically scalable, corresponding computational methods building on these findings have emerged; however, these are not accurate enough for annotation of genomes. The limitations reflect that we have no accurate universal model describing transcription initiation; to a large extent, our understanding is based on case stories. Recently, high-throughput methods have been developed to chart the TSS landscape with nucleotide resolution. Using these data, I have dissected promoters at nucleotide level and found patterns that explain the transcription initiation rate for individual nucleotides. The objective for this work is to extend this to the first universal model for how cells select core promoters and associated TSSs. This will have two counterparts: i)prediction of TSSs from DNA sequence given a region of accessible DNA, and ii)prediction of DNA accessibility based on DNA sequences and dynamic epigenetic factors. Such a model will be a corner stone of future experimental and computational transcriptome and gene regulation studies.
Max ERC Funding
812 399 €
Duration
Start date: 2008-09-01, End date: 2013-08-31
Project acronym DUB-DECODE
Project Systematic Decoding of Deubiquitylase-Regulated Signaling Networks
Researcher (PI) Chuna Ram Choudhary
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Consolidator Grant (CoG), LS2, ERC-2014-CoG
Summary Cellular processes are largely governed by sophisticated protein posttranslational modification (PTM)-dependent signaling networks, and a systematic understanding of regulatory PTM-based networks is a key goal in modern biology. Ubiquitin is a small, evolutionarily conserved signaling protein that acts as a PTM after being covalently conjugated to other proteins. Reversible ubiquitylation forms the most versatile and largest eukaryote-exclusive signaling system, and regulates the stability and function of almost all proteins in cells. Deubiquitylases (DUBs) are ubiquitin-specific proteases that remove substrate-conjugated ubiquitin, and thereby regulate virtually all ubiquitylation-dependent signaling. Because of their central role in ubiquitin signaling, DUBs have essential functions in mammalian physiology and development, and the dysregulated expression and mutation of DUBs is frequently associated with human diseases. Despite their vital functions, very little is known about the proteins and ubiquitylation sites that are regulated by DUBs and this knowledge gap is hampering our understanding of the molecular mechanisms by which DUBs control diverse biological processes. Recently, we developed a mass spectrometry-based proteomics approach that allowed unbiased and site-specific quantification of ubiquitylation on a systems-wide scale. Here we propose to comprehensively investigate DUB-regulated ubiquitin signaling in human cells. We will integrate interdisciplinary approaches to develop next-generation cell models and innovative proteomic technologies to systematically decode DUB function in human cells. This will enable a novel and detailed understanding of DUB-regulated signaling networks, and open up new avenues for further research into the mechanisms and biological functions of ubiquitylation and of ubiquitin-like modifiers.
Summary
Cellular processes are largely governed by sophisticated protein posttranslational modification (PTM)-dependent signaling networks, and a systematic understanding of regulatory PTM-based networks is a key goal in modern biology. Ubiquitin is a small, evolutionarily conserved signaling protein that acts as a PTM after being covalently conjugated to other proteins. Reversible ubiquitylation forms the most versatile and largest eukaryote-exclusive signaling system, and regulates the stability and function of almost all proteins in cells. Deubiquitylases (DUBs) are ubiquitin-specific proteases that remove substrate-conjugated ubiquitin, and thereby regulate virtually all ubiquitylation-dependent signaling. Because of their central role in ubiquitin signaling, DUBs have essential functions in mammalian physiology and development, and the dysregulated expression and mutation of DUBs is frequently associated with human diseases. Despite their vital functions, very little is known about the proteins and ubiquitylation sites that are regulated by DUBs and this knowledge gap is hampering our understanding of the molecular mechanisms by which DUBs control diverse biological processes. Recently, we developed a mass spectrometry-based proteomics approach that allowed unbiased and site-specific quantification of ubiquitylation on a systems-wide scale. Here we propose to comprehensively investigate DUB-regulated ubiquitin signaling in human cells. We will integrate interdisciplinary approaches to develop next-generation cell models and innovative proteomic technologies to systematically decode DUB function in human cells. This will enable a novel and detailed understanding of DUB-regulated signaling networks, and open up new avenues for further research into the mechanisms and biological functions of ubiquitylation and of ubiquitin-like modifiers.
Max ERC Funding
1 972 570 €
Duration
Start date: 2015-10-01, End date: 2020-09-30
Project acronym EQU
Project Exploring the Quantum Universe
Researcher (PI) Jan Ambjørn
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Advanced Grant (AdG), PE2, ERC-2011-ADG_20110209
Summary "One of the main unsolved problems in theoretical physics today is to reconcile the theories of general relativity and quantum mechanics. The starting point of this proposal is a new background-independent theory of quantum gravity, which has been constructed from first principles as a sum over space-time histories and has already passed its first non-trivial tests. The theory can be investigated analytically as well as by Monte Carlo simulations. The aim is to verify that it is a viable theory of quantum gravity. Thus we want to show that it has the correct long-distance behaviour (classical Einstein gravity) and to investigate its short-distance behaviour in detail. We expect new physics to show up at the shortest distances, physics which might help us understand the origin of our universe and why the universe looks the way we observe today."
Summary
"One of the main unsolved problems in theoretical physics today is to reconcile the theories of general relativity and quantum mechanics. The starting point of this proposal is a new background-independent theory of quantum gravity, which has been constructed from first principles as a sum over space-time histories and has already passed its first non-trivial tests. The theory can be investigated analytically as well as by Monte Carlo simulations. The aim is to verify that it is a viable theory of quantum gravity. Thus we want to show that it has the correct long-distance behaviour (classical Einstein gravity) and to investigate its short-distance behaviour in detail. We expect new physics to show up at the shortest distances, physics which might help us understand the origin of our universe and why the universe looks the way we observe today."
Max ERC Funding
2 187 286 €
Duration
Start date: 2012-07-01, End date: 2017-06-30
Project acronym Extinction Genomics
Project Exploring and exploiting the potential of extinct genome sequencing
Researcher (PI) Marcus Thomas Pius Gilbert
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Consolidator Grant (CoG), LS2, ERC-2015-CoG
Summary Palaeogenomics is the nascent discipline concerned with sequencing and analysis of genome-scale information from historic, ancient, and even extinct samples. While once inconceivable due to the challenges of DNA damage, contamination, and the technical limitations of PCR-based Sanger sequencing, following the dawn of the second-generation sequencing revolution, it has rapidly become a reality. Indeed, so much so, that popular perception has moved away from if extinct species’ genomes can be sequenced, to when it will happen - and even, when will the first extinct animals be regenerated. Unfortunately this view is naïve, and does not account for the financial and technical challenges that face such attempts. I propose an exploration of exactly what the limits on genome reconstruction from extinct or otherwise historic/ancient material are. This will be achieved through new laboratory and bioinformatic developments aimed at decreasing the cost, while concomitantly increasing the quality of genome reconstruction from poor quality materials. In doing so I aim to build a scientifically-grounded framework against which the possibilities and limitations of extinct genome reconstruction can be assessed. Subsequently genomic information will be generated from a range of extinct and near-extinct avian and mammalian species, in order to showcase the potential of reconstructed genomes across research questions spanning at least three different streams of research: De-extinction, Evolutionary Genomics, and Conservation Genomics. Ultimately, achievement of these goals requires formation of a dedicated, closely knit team, focusing on both the methodological challenges as well as their bigger picture application to high-risk high-gain ventures. With ERC funding this can become a reality, and enable palaeogenomics to be pushed to the limits possible under modern technology.
Summary
Palaeogenomics is the nascent discipline concerned with sequencing and analysis of genome-scale information from historic, ancient, and even extinct samples. While once inconceivable due to the challenges of DNA damage, contamination, and the technical limitations of PCR-based Sanger sequencing, following the dawn of the second-generation sequencing revolution, it has rapidly become a reality. Indeed, so much so, that popular perception has moved away from if extinct species’ genomes can be sequenced, to when it will happen - and even, when will the first extinct animals be regenerated. Unfortunately this view is naïve, and does not account for the financial and technical challenges that face such attempts. I propose an exploration of exactly what the limits on genome reconstruction from extinct or otherwise historic/ancient material are. This will be achieved through new laboratory and bioinformatic developments aimed at decreasing the cost, while concomitantly increasing the quality of genome reconstruction from poor quality materials. In doing so I aim to build a scientifically-grounded framework against which the possibilities and limitations of extinct genome reconstruction can be assessed. Subsequently genomic information will be generated from a range of extinct and near-extinct avian and mammalian species, in order to showcase the potential of reconstructed genomes across research questions spanning at least three different streams of research: De-extinction, Evolutionary Genomics, and Conservation Genomics. Ultimately, achievement of these goals requires formation of a dedicated, closely knit team, focusing on both the methodological challenges as well as their bigger picture application to high-risk high-gain ventures. With ERC funding this can become a reality, and enable palaeogenomics to be pushed to the limits possible under modern technology.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-04-01, End date: 2021-03-31
Project acronym HBAR12
Project Spectroscopy of Trapped Antihydrogen
Researcher (PI) Jeffrey Scott Hangst
Host Institution (HI) AARHUS UNIVERSITET
Call Details Advanced Grant (AdG), PE2, ERC-2012-ADG_20120216
Summary Antihydrogen is the only stable, neutral antimatter system available for laboratory study. Recently, the ALPHA Collaboration at CERN has succeeded in synthesizing and trapping antihydrogen atoms, storing them for up to 1000 s, and performing the first resonant spectroscopy, using microwaves, on trapped antihydrogen. This last, historic result paves the way for precision microwave and laser spectroscopic measurements using small numbers of trapped antihydrogen atoms. Because of the breakthroughs made in our collaboration, it is now possible, for the first time, to design antimatter spectroscopic experiments that have achievable milestones of precision. These measurements require a next-generation apparatus, known as ALPHA-2, which is the subject of this proposal. The items sought are hardware components and radiation sources to help us to test CPT (charge conjugation, parity, time reversal) symmetry invariance by comparing the spectrum of antihydrogen to that of hydrogen. More generally, we will address the very fundamental question: do matter and antimatter obey the same laws of physics? The Standard Model says that they must, but mystery continues to cloud our understanding of antimatter - as evidenced by the unexplained baryon asymmetry in the universe. ALPHA's experiments offer a unique, high precision, model-independent view into the internal workings of antimatter.
Summary
Antihydrogen is the only stable, neutral antimatter system available for laboratory study. Recently, the ALPHA Collaboration at CERN has succeeded in synthesizing and trapping antihydrogen atoms, storing them for up to 1000 s, and performing the first resonant spectroscopy, using microwaves, on trapped antihydrogen. This last, historic result paves the way for precision microwave and laser spectroscopic measurements using small numbers of trapped antihydrogen atoms. Because of the breakthroughs made in our collaboration, it is now possible, for the first time, to design antimatter spectroscopic experiments that have achievable milestones of precision. These measurements require a next-generation apparatus, known as ALPHA-2, which is the subject of this proposal. The items sought are hardware components and radiation sources to help us to test CPT (charge conjugation, parity, time reversal) symmetry invariance by comparing the spectrum of antihydrogen to that of hydrogen. More generally, we will address the very fundamental question: do matter and antimatter obey the same laws of physics? The Standard Model says that they must, but mystery continues to cloud our understanding of antimatter - as evidenced by the unexplained baryon asymmetry in the universe. ALPHA's experiments offer a unique, high precision, model-independent view into the internal workings of antimatter.
Max ERC Funding
2 136 888 €
Duration
Start date: 2013-05-01, End date: 2018-12-31
Project acronym Interface
Project Quantum Optical Interfaces for Atoms and Nano-electro-mechanical Systems
Researcher (PI) Eugene Polzik
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Advanced Grant (AdG), PE2, ERC-2011-ADG_20110209
Summary Quantum interfaces capable of transferring quantum states and generating entanglement between fields and matter are set to play a growing role in the development of science and technology. Development of such interfaces has been a crucial component in quantum information processing and communication. In the past decade quantum interfaces between atoms and optical photons have been extensively explored by a number of leading groups. Quantum state transfer between light and atoms, such as quantum memory and quantum teleportation, entanglement of massive objects, as well as measurements and sensing beyond standard quantum limits have been demonstrated by the group of the PI.
We propose to develop a robust, integrated and scalable atom-light interface and to incorporate it into a hybrid multi-facet quantum network with other relevant quantum systems, such as nano-mechanical oscillators and electronic circuits.
Towards this ambitious goal we will develop room temperature atomic quantum memories in spin protecting micro-cells (mu-cells) and opto-mechanical and electromechanical strongly coupled systems. Interfacing atoms, electronic circuits and nano-mechanical oscillators we will perform ultrasensitive quantum limited field and force measurements and quantum teleportation of states across the range of these systems.
In the fundamental sense, this research program will further broaden the horizons of quantum physics and quantum information processing by expanding it into new and unexplored macroscopic domains.
Summary
Quantum interfaces capable of transferring quantum states and generating entanglement between fields and matter are set to play a growing role in the development of science and technology. Development of such interfaces has been a crucial component in quantum information processing and communication. In the past decade quantum interfaces between atoms and optical photons have been extensively explored by a number of leading groups. Quantum state transfer between light and atoms, such as quantum memory and quantum teleportation, entanglement of massive objects, as well as measurements and sensing beyond standard quantum limits have been demonstrated by the group of the PI.
We propose to develop a robust, integrated and scalable atom-light interface and to incorporate it into a hybrid multi-facet quantum network with other relevant quantum systems, such as nano-mechanical oscillators and electronic circuits.
Towards this ambitious goal we will develop room temperature atomic quantum memories in spin protecting micro-cells (mu-cells) and opto-mechanical and electromechanical strongly coupled systems. Interfacing atoms, electronic circuits and nano-mechanical oscillators we will perform ultrasensitive quantum limited field and force measurements and quantum teleportation of states across the range of these systems.
In the fundamental sense, this research program will further broaden the horizons of quantum physics and quantum information processing by expanding it into new and unexplored macroscopic domains.
Max ERC Funding
2 493 000 €
Duration
Start date: 2012-07-01, End date: 2017-06-30
Project acronym KINOMEDRIFT
Project Specificity Drift in The Kinome During Cancer Development and Evolution
Researcher (PI) Rune Linding Raun
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), LS2, ERC-2012-StG_20111109
Summary "Cellular signaling networks have evolved to enable swift and accurate responses, even in the face of genetic or environmental perturbation. While we can readily assess dynamics in phosphorylation sites, our ability to model and predict the associated networks of kinases are hampered by the fact that we lack information on catalytic specificity for around 60% of the 538 human protein kinases (kinome). This translates into an even bigger gap in kinase-substrate relationships, where a phosphorylating kinase is only known for 20% of all known phosphorylation sites. The importance of closing these gaps is underlined by the fact that kinases are the target of about 75% of current world-wide drug development programs, and it is increasingly evident that they must be targeted in combinations, as elucidated by network models.
While genomic studies are revealing large numbers of mutations in kinases in most cancers, algorithms that can assess which of these are important for tumor growth and disease progression are missing. Thus, there is a critical need for algorithms that can predict how such lesions affect the catalytic specificity of kinases. These challenges must be resolved before we can predict how combinations of genetic alterations affect networks and thereby drive complex phenotypes and diseases.
The main objective of this grant is to explore the specificity space of kinases through a combination of experimental and computational approaches. We shall investigate how specificity in cellular signaling systems may be altered during both natural evolution and cancer development. We will develop a new generation of network biology algorithms to enable interpretation of mutations in the kinase domain. In combination with semi-automated specificity and mass-spectrometry interaction screening of hundreds of kinases, we shall deploy these algorithms to specifically identify drift in natural selection of kinase specificity as well as in fast evolving cancer genomes."
Summary
"Cellular signaling networks have evolved to enable swift and accurate responses, even in the face of genetic or environmental perturbation. While we can readily assess dynamics in phosphorylation sites, our ability to model and predict the associated networks of kinases are hampered by the fact that we lack information on catalytic specificity for around 60% of the 538 human protein kinases (kinome). This translates into an even bigger gap in kinase-substrate relationships, where a phosphorylating kinase is only known for 20% of all known phosphorylation sites. The importance of closing these gaps is underlined by the fact that kinases are the target of about 75% of current world-wide drug development programs, and it is increasingly evident that they must be targeted in combinations, as elucidated by network models.
While genomic studies are revealing large numbers of mutations in kinases in most cancers, algorithms that can assess which of these are important for tumor growth and disease progression are missing. Thus, there is a critical need for algorithms that can predict how such lesions affect the catalytic specificity of kinases. These challenges must be resolved before we can predict how combinations of genetic alterations affect networks and thereby drive complex phenotypes and diseases.
The main objective of this grant is to explore the specificity space of kinases through a combination of experimental and computational approaches. We shall investigate how specificity in cellular signaling systems may be altered during both natural evolution and cancer development. We will develop a new generation of network biology algorithms to enable interpretation of mutations in the kinase domain. In combination with semi-automated specificity and mass-spectrometry interaction screening of hundreds of kinases, we shall deploy these algorithms to specifically identify drift in natural selection of kinase specificity as well as in fast evolving cancer genomes."
Max ERC Funding
1 700 000 €
Duration
Start date: 2012-11-01, End date: 2016-10-31
Project acronym LimitMDR
Project Utilizing evolutionary interactions to limit multidrug resistance
Researcher (PI) Morten Otto Alexander Sommer
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Starting Grant (StG), LS2, ERC-2014-STG
Summary Drug resistance is limiting our ability to treat most infectious diseases and forms of cancer. Indeed this relentless evolution is the major driver of treatment failure for diseases that are responsible for over half of the global disease related mortality. Yet, the underlying principles that guide this evolutionary response are poorly understood, in particular with regards to understanding the impact of multidrug treatment.
LimitMDR will characterize evolutionary trajectories leading to multidrug resistance in response to individual and combination drug treatment through the execution of large-scale adaptive evolution experiment with two bacterial pathogens followed by genome sequencing and phenotyping. This effort will enable testing of contrasting hypotheses regarding the evolution of multidrug resistance in response to combination treatment.
We will characterize the cause-and-effect of resistance and sensitivity mutations identified in our global data set and map comprehensive fitness landscapes of mutations accumulated during drug resistance evolution to understand the evolutionary dynamics underlying resistance evolution. To accomplish these bold goals we shall develop novel multiplexed methodologies enabling unprecedented scale of construction and phenotypic testing of identified mutations. While genetic epistasis is considered of key importance to resistance evolution most studies focus on mutations within an individual gene. Through the development of a novel experimental approach we shall elucidate complex epistatic interaction networks between mutations accumulated during resistance evolution.
Finally, we will conduct mechanistic studies to uncover the mechanisms of collateral sensitivity. These studies will shed light on this underappreciated phenomenon, which is of critical relevance to drug discovery and the evolution of drug resistance. In conclusion LimitMDR will develop groundbreaking novel methodologies and scientific insights that will c
Summary
Drug resistance is limiting our ability to treat most infectious diseases and forms of cancer. Indeed this relentless evolution is the major driver of treatment failure for diseases that are responsible for over half of the global disease related mortality. Yet, the underlying principles that guide this evolutionary response are poorly understood, in particular with regards to understanding the impact of multidrug treatment.
LimitMDR will characterize evolutionary trajectories leading to multidrug resistance in response to individual and combination drug treatment through the execution of large-scale adaptive evolution experiment with two bacterial pathogens followed by genome sequencing and phenotyping. This effort will enable testing of contrasting hypotheses regarding the evolution of multidrug resistance in response to combination treatment.
We will characterize the cause-and-effect of resistance and sensitivity mutations identified in our global data set and map comprehensive fitness landscapes of mutations accumulated during drug resistance evolution to understand the evolutionary dynamics underlying resistance evolution. To accomplish these bold goals we shall develop novel multiplexed methodologies enabling unprecedented scale of construction and phenotypic testing of identified mutations. While genetic epistasis is considered of key importance to resistance evolution most studies focus on mutations within an individual gene. Through the development of a novel experimental approach we shall elucidate complex epistatic interaction networks between mutations accumulated during resistance evolution.
Finally, we will conduct mechanistic studies to uncover the mechanisms of collateral sensitivity. These studies will shed light on this underappreciated phenomenon, which is of critical relevance to drug discovery and the evolution of drug resistance. In conclusion LimitMDR will develop groundbreaking novel methodologies and scientific insights that will c
Max ERC Funding
1 492 453 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym LOBENA
Project Long Beamtime Experiments for Nuclear Astrophysics
Researcher (PI) Hans Otto Uldall Fynbo
Host Institution (HI) AARHUS UNIVERSITET
Call Details Starting Grant (StG), PE2, ERC-2012-StG_20111012
Summary The goal of LOBENA is to measure key properties needed for understanding nuclear processes in the Cosmos. Nuclear Astrophysics plays a key role in our quest to understand the origin and distribution of the chemical elements in our galaxy. Nuclear processes are crucial for understanding the energy production in the universe and are essential for describing the creation of chemical elements from the ashes of the Big Bang. Uncertainties in the nuclear physics can therefore influence our understanding of many astrophysical processes, both those involving stable stellar burning phases and explosive phenomena such as X-ray bursts, gamma-ray bursts and supernovae.
In LOBENA (LOng Beamtime Experiments for Nuclear Astrophysics) I will initiate a series of studies in Nuclear Astrophysics, which have in common the need for long beam times and the use of complete kinematics detection of several particles emitted in reactions. The core of the project will focus on the systems 8Be, 12C and 16O where today key open questions of great importance remain to answered. These questions can be addressed by reactions induced by low energy (<5MeV) beams of protons and 3He on light targets such as 6,7Li, 9Be, 10,11B and 19F using a newly developed complete kinematics detection procedure. The department of Physics and Astronomy in Aarhus provides a unique scene for doing these measurements since it provides accelerators where long beam time can be guarantied. LOBENA will also include complimentary experiments at international user facilities such as ISOLDE (CERN), KVI (Groningen), JYFL and (Jyväskylä).
With this ERC starting grant proposal I wish to start up my own group around Nuclear Astrophysics experiments in house and at international user facilities. With two Post Doc.s and a Ph.D. I will be much better able to fully exploit the scientific potential of the proposed research, which will also help to consolidate my own research career and give me more independence.
Summary
The goal of LOBENA is to measure key properties needed for understanding nuclear processes in the Cosmos. Nuclear Astrophysics plays a key role in our quest to understand the origin and distribution of the chemical elements in our galaxy. Nuclear processes are crucial for understanding the energy production in the universe and are essential for describing the creation of chemical elements from the ashes of the Big Bang. Uncertainties in the nuclear physics can therefore influence our understanding of many astrophysical processes, both those involving stable stellar burning phases and explosive phenomena such as X-ray bursts, gamma-ray bursts and supernovae.
In LOBENA (LOng Beamtime Experiments for Nuclear Astrophysics) I will initiate a series of studies in Nuclear Astrophysics, which have in common the need for long beam times and the use of complete kinematics detection of several particles emitted in reactions. The core of the project will focus on the systems 8Be, 12C and 16O where today key open questions of great importance remain to answered. These questions can be addressed by reactions induced by low energy (<5MeV) beams of protons and 3He on light targets such as 6,7Li, 9Be, 10,11B and 19F using a newly developed complete kinematics detection procedure. The department of Physics and Astronomy in Aarhus provides a unique scene for doing these measurements since it provides accelerators where long beam time can be guarantied. LOBENA will also include complimentary experiments at international user facilities such as ISOLDE (CERN), KVI (Groningen), JYFL and (Jyväskylä).
With this ERC starting grant proposal I wish to start up my own group around Nuclear Astrophysics experiments in house and at international user facilities. With two Post Doc.s and a Ph.D. I will be much better able to fully exploit the scientific potential of the proposed research, which will also help to consolidate my own research career and give me more independence.
Max ERC Funding
1 476 075 €
Duration
Start date: 2012-11-01, End date: 2018-10-31
Project acronym LONGEVITYBYCAUSE
Project Cause of Death Contribution to Longevity: Modeling Time Trends
Researcher (PI) Vladimir Canudas Romo
Host Institution (HI) SYDDANSK UNIVERSITET
Call Details Starting Grant (StG), SH3, ERC-2009-StG
Summary Since the mid-nineteen century life expectancy in developed countries has doubled, increasing from levels around 40 years to above 80 years. This research project is motivated by the need to further explore how societies have achieved the current levels of longevity, in terms of life expectancy and modal age at death. To achieve this, age-patterns and time-trends in cause of death contribution to longevity are assessed. This historical analysis is carried out in fifty developed and developing countries/areas. It is expected that the cause of death contribution to the advancement of longevity is country/region specific. However, the hypothesis to be tested is that there are common cause-specific time-trends across countries which can be described by a model of cause of death contribution to longevity. Several purposes for such a model can be listed: it will allow us to study expected future mortality directions in developed nations that are currently still facing high levels of some particular causes of death, e.g. the Netherlands and United States. It could also help investigating the retrocession in mortality observed in some transitional countries/areas, particularly in Eastern Europe. Finally, the accelerated epidemiological transition in developing countries is compared to the slower trend in the developed world at earlier times, model results versus observed cause-contribution. The interest in the latter comparison is to foresee the increase in the prevalence of chronic disease in low-income countries predicted by the WHO and the World Bank. Furthermore, one in every three countries in the world has adequate cause-specific mortality data. The proposed model could facilitate estimating the current cause of death status in developing countries. This project addresses a significant question concerning the mechanisms (age and cause of death) that direct reductions in mortality.
Summary
Since the mid-nineteen century life expectancy in developed countries has doubled, increasing from levels around 40 years to above 80 years. This research project is motivated by the need to further explore how societies have achieved the current levels of longevity, in terms of life expectancy and modal age at death. To achieve this, age-patterns and time-trends in cause of death contribution to longevity are assessed. This historical analysis is carried out in fifty developed and developing countries/areas. It is expected that the cause of death contribution to the advancement of longevity is country/region specific. However, the hypothesis to be tested is that there are common cause-specific time-trends across countries which can be described by a model of cause of death contribution to longevity. Several purposes for such a model can be listed: it will allow us to study expected future mortality directions in developed nations that are currently still facing high levels of some particular causes of death, e.g. the Netherlands and United States. It could also help investigating the retrocession in mortality observed in some transitional countries/areas, particularly in Eastern Europe. Finally, the accelerated epidemiological transition in developing countries is compared to the slower trend in the developed world at earlier times, model results versus observed cause-contribution. The interest in the latter comparison is to foresee the increase in the prevalence of chronic disease in low-income countries predicted by the WHO and the World Bank. Furthermore, one in every three countries in the world has adequate cause-specific mortality data. The proposed model could facilitate estimating the current cause of death status in developing countries. This project addresses a significant question concerning the mechanisms (age and cause of death) that direct reductions in mortality.
Max ERC Funding
300 380 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym MECTRL
Project Measurement-based dynamic control of mesoscopic many-body systems
Researcher (PI) Jacob Friis Sherson
Host Institution (HI) AARHUS UNIVERSITET
Call Details Starting Grant (StG), PE2, ERC-2014-STG
Summary Quantum control is an ambitious framework for steering dynamics from initial states to arbitrary desired final states. It has over the past decade been used extensively with immense success for control of low- dimensional systems in as varied fields as molecular dynamics and quantum computation. Only recently have efforts been initiated to extend this to higher-dimensional many-body systems. Most generic quantum control schemes to date, however, put quite heavy requirements on the controllability of either the system Hamiltonian or a set of measurement operators. This will in many realistic scenarios prohibit an efficient realization.
Within this proposal, I will develop a new quantum control scheme, which is minimalistic on system requirements and therefore ideally suited for the efficient and reliable optimization of many-body control problems. The fundamentally new ingredient is the total quantum evolution dictated by a combination of fixed many-body time evolution and the precise knowledge of the quantum back-action due to repeated quantum non-destruction (QND) measurements of a single projection operator.
The main focus of this proposal is theoretical and experimental quantum engineering of the dynamics in systems, which are sufficiently small to calculate the measurement back-action exactly and sufficiently large to have interesting many-body properties.
Recent experimental advances in single site manipulation of bosons in optical lattices have enabled the high fidelity preparation exactly such mesoscopic samples of atoms (5-50). This forms an ideal starting point for many-body quantum control, and we will i.a. demonstrate engineering of quantum phase transitions and preparation of highly non-classical Schödinger cat states.
Finally, using the results from an online graphical interface allowing users of the internet to solve quantum problems we will attempt to build next-generation optimization computer algorithms with a higher level of cognition built in.
Summary
Quantum control is an ambitious framework for steering dynamics from initial states to arbitrary desired final states. It has over the past decade been used extensively with immense success for control of low- dimensional systems in as varied fields as molecular dynamics and quantum computation. Only recently have efforts been initiated to extend this to higher-dimensional many-body systems. Most generic quantum control schemes to date, however, put quite heavy requirements on the controllability of either the system Hamiltonian or a set of measurement operators. This will in many realistic scenarios prohibit an efficient realization.
Within this proposal, I will develop a new quantum control scheme, which is minimalistic on system requirements and therefore ideally suited for the efficient and reliable optimization of many-body control problems. The fundamentally new ingredient is the total quantum evolution dictated by a combination of fixed many-body time evolution and the precise knowledge of the quantum back-action due to repeated quantum non-destruction (QND) measurements of a single projection operator.
The main focus of this proposal is theoretical and experimental quantum engineering of the dynamics in systems, which are sufficiently small to calculate the measurement back-action exactly and sufficiently large to have interesting many-body properties.
Recent experimental advances in single site manipulation of bosons in optical lattices have enabled the high fidelity preparation exactly such mesoscopic samples of atoms (5-50). This forms an ideal starting point for many-body quantum control, and we will i.a. demonstrate engineering of quantum phase transitions and preparation of highly non-classical Schödinger cat states.
Finally, using the results from an online graphical interface allowing users of the internet to solve quantum problems we will attempt to build next-generation optimization computer algorithms with a higher level of cognition built in.
Max ERC Funding
1 499 406 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym Micromecca
Project Molecular mechanisms underlying plant miRNA action
Researcher (PI) Anders Peter Brodersen
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), LS2, ERC-2011-StG_20101109
Summary MicroRNAs (miRNAs) are 20-22 nt non-coding RNAs that regulate gene expression post transcriptionally via base pairing to complementary target mRNAs. They have fundamental importance for development and stress adaptation in plants and animals. Although a molecular frame work for miRNA biogenesis, degradation and action has been established, many aspects of this important gene regulatory pathway remain unknown. This project explores four main points. First, we propose to use genetic approaches to identify factors required for translational repression by miRNAs in plants. This mode of action was until recently thought to occur only exceptionally in plants. My post doctoral work showed that it occurs in many miRNA-target interactions. The mechanism remains unknown, however, leaving open a fertile area of investigation. Second, we wish to test specific hypotheses regarding the in vivo role of miRNA mediated endonucleolysis of mRNA targets. Long believed to serve exclusively as a degradation mechanism, we propose to test whether this process could have important functions in biogenesis of long non-coding RNA derived from mRNAs.
Third, my postdoctoral work has provided unique material to use molecular genetics to explore pathways responsible for miRNA degradation, an aspect of miRNA biology that only now is emerging as being of major importance. Finally, our unpublished results show that plant miRNAs and their associated effector protein Argonaute (AGO) are associated with membranes and that membrane association is crucial for function. This is in line with similar data recently obtained from different animal systems. We propose to use genetic, biochemical and cell biological approaches to clarify to which membrane compartment AGO and miRNAs are associated, how they are recruited to this compartment, and what the precise function of membrane association is.
These innovative approaches promise to give fundamental new insights into the inner workings of the pathway.
Summary
MicroRNAs (miRNAs) are 20-22 nt non-coding RNAs that regulate gene expression post transcriptionally via base pairing to complementary target mRNAs. They have fundamental importance for development and stress adaptation in plants and animals. Although a molecular frame work for miRNA biogenesis, degradation and action has been established, many aspects of this important gene regulatory pathway remain unknown. This project explores four main points. First, we propose to use genetic approaches to identify factors required for translational repression by miRNAs in plants. This mode of action was until recently thought to occur only exceptionally in plants. My post doctoral work showed that it occurs in many miRNA-target interactions. The mechanism remains unknown, however, leaving open a fertile area of investigation. Second, we wish to test specific hypotheses regarding the in vivo role of miRNA mediated endonucleolysis of mRNA targets. Long believed to serve exclusively as a degradation mechanism, we propose to test whether this process could have important functions in biogenesis of long non-coding RNA derived from mRNAs.
Third, my postdoctoral work has provided unique material to use molecular genetics to explore pathways responsible for miRNA degradation, an aspect of miRNA biology that only now is emerging as being of major importance. Finally, our unpublished results show that plant miRNAs and their associated effector protein Argonaute (AGO) are associated with membranes and that membrane association is crucial for function. This is in line with similar data recently obtained from different animal systems. We propose to use genetic, biochemical and cell biological approaches to clarify to which membrane compartment AGO and miRNAs are associated, how they are recruited to this compartment, and what the precise function of membrane association is.
These innovative approaches promise to give fundamental new insights into the inner workings of the pathway.
Max ERC Funding
1 459 011 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym PATHORISC
Project Reprogramming of small RNA function in plant-pathogen interactions
Researcher (PI) Anders Peter BRODERSEN
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Consolidator Grant (CoG), LS2, ERC-2016-COG
Summary RNA silencing relies on small RNAs that act in RNA induced silencing complexes (RISCs). RISCs use base pairing to select mRNAs or invading nucleic acids such as viruses for repression. RNA silencing may facilitate gene expression changes, for example in host-pathogen interactions. Such changes require reprogramming of RISC, since a different set of RNAs must be rapidly repressed upon pathogen perception. RISC reprogramming is non-trivial: new small RNAs must be produced and be rapidly incorporated into RISC, while unwanted repression by pre-existing RISCs must be eliminated. This project focuses on understanding three central aspects of RISC reprogramming in plant-pathogen interactions. First, we will define mechanisms that allow invading RNA, but not self-RNA, to engage in positive feedback loops for small RNA synthesis, and we will investigate the specific importance of these positive feedback loops in antiviral defense. Second, we will explore how rapid proteolysis of the central RISC component ARGONAUTE1 (AGO1) governs rapid incorporation of newly synthesized small RNA. We will also explore the hypothesis that non-RNA bound AGO1 is degraded to minimize vulnerability to pathogens that use small RNAs as virulence factors to repress host immune signaling. The relevance of these mechanisms of AGO1 proteolysis in plant immunity will be investigated. These studies take advantage of our recent discovery of proteins required specifically for turnover of AGO1. Finally, we explore the hypothesis that rapid chemical modification of mRNA by N6-adenosine methylation (m6A) may bring mRNAs with poor small RNA binding sites under RISC repression. This scenario is supported by interactions between m6A reader proteins and AGO1 discovered in current work in the group. This mechanism may enable reprogramming of RISC specificity rather than composition upon pathogen perception. Our project will fill gaps in knowledge on RNA silencing and elucidate their importance in plant immunity.
Summary
RNA silencing relies on small RNAs that act in RNA induced silencing complexes (RISCs). RISCs use base pairing to select mRNAs or invading nucleic acids such as viruses for repression. RNA silencing may facilitate gene expression changes, for example in host-pathogen interactions. Such changes require reprogramming of RISC, since a different set of RNAs must be rapidly repressed upon pathogen perception. RISC reprogramming is non-trivial: new small RNAs must be produced and be rapidly incorporated into RISC, while unwanted repression by pre-existing RISCs must be eliminated. This project focuses on understanding three central aspects of RISC reprogramming in plant-pathogen interactions. First, we will define mechanisms that allow invading RNA, but not self-RNA, to engage in positive feedback loops for small RNA synthesis, and we will investigate the specific importance of these positive feedback loops in antiviral defense. Second, we will explore how rapid proteolysis of the central RISC component ARGONAUTE1 (AGO1) governs rapid incorporation of newly synthesized small RNA. We will also explore the hypothesis that non-RNA bound AGO1 is degraded to minimize vulnerability to pathogens that use small RNAs as virulence factors to repress host immune signaling. The relevance of these mechanisms of AGO1 proteolysis in plant immunity will be investigated. These studies take advantage of our recent discovery of proteins required specifically for turnover of AGO1. Finally, we explore the hypothesis that rapid chemical modification of mRNA by N6-adenosine methylation (m6A) may bring mRNAs with poor small RNA binding sites under RISC repression. This scenario is supported by interactions between m6A reader proteins and AGO1 discovered in current work in the group. This mechanism may enable reprogramming of RISC specificity rather than composition upon pathogen perception. Our project will fill gaps in knowledge on RNA silencing and elucidate their importance in plant immunity.
Max ERC Funding
1 987 811 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym PUNCTUATION
Project Pervasive Upstream Non-Coding Transcription Underpinning Adaptation
Researcher (PI) Andreas Sebastian Marquardt
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), LS2, ERC-2017-STG
Summary Genomic DNA represents the blueprint of life: it instructs solutions to challenges during life cycles of organisms. Curiously DNA in higher organisms is mostly non-protein coding (e.g. 97% in human). The popular “junk-DNA” hypothesis postulates that this non-coding DNA is non-functional. However, high-throughput transcriptomics indicates that this may be an over-simplification as most non-coding DNA is transcribed. This pervasive transcription yields two molecular events that may be functional: 1.) resulting long non-coding RNA (lncRNA) molecules, and 2.) the act of pervasive transcription itself. Whereas lncRNA sequences and functions differ on a case-by-case basis, RNA polymerase II (Pol II) transcribes most lncRNA. Pol II activity leaves molecular marks that specify transcription stages. The profiles of stage-specific activities instruct separation and fidelity of transcription units (genomic punctuation). Pervasive transcription affects genomic punctuation: upstream lncRNA transcription over gene promoters can repress downstream gene expression, also referred to as tandem Transcriptional Interference (tTI). Even though tTI was first reported decades ago a systematic characterization of tTI is lacking. Guided by my expertise in lncRNA transcription I recently identified the genetic material to dissect tTI in plants as an independent group leader. My planned research promises to reveal the genetic architecture and the molecular hallmarks defining tTI in higher organisms. Environmental lncRNA transcription variability may trigger tTI to promote organismal responses to changing conditions. We will address the roles of tTI in plant cold response to test this hypothesis. I anticipate our findings to inform on the fraction of pervasive transcription engaging in tTI. My proposal promises to advance our understanding of genomes by reconciling how the transcription of variable non-coding DNA sequences can elicit equivalent functions.
Summary
Genomic DNA represents the blueprint of life: it instructs solutions to challenges during life cycles of organisms. Curiously DNA in higher organisms is mostly non-protein coding (e.g. 97% in human). The popular “junk-DNA” hypothesis postulates that this non-coding DNA is non-functional. However, high-throughput transcriptomics indicates that this may be an over-simplification as most non-coding DNA is transcribed. This pervasive transcription yields two molecular events that may be functional: 1.) resulting long non-coding RNA (lncRNA) molecules, and 2.) the act of pervasive transcription itself. Whereas lncRNA sequences and functions differ on a case-by-case basis, RNA polymerase II (Pol II) transcribes most lncRNA. Pol II activity leaves molecular marks that specify transcription stages. The profiles of stage-specific activities instruct separation and fidelity of transcription units (genomic punctuation). Pervasive transcription affects genomic punctuation: upstream lncRNA transcription over gene promoters can repress downstream gene expression, also referred to as tandem Transcriptional Interference (tTI). Even though tTI was first reported decades ago a systematic characterization of tTI is lacking. Guided by my expertise in lncRNA transcription I recently identified the genetic material to dissect tTI in plants as an independent group leader. My planned research promises to reveal the genetic architecture and the molecular hallmarks defining tTI in higher organisms. Environmental lncRNA transcription variability may trigger tTI to promote organismal responses to changing conditions. We will address the roles of tTI in plant cold response to test this hypothesis. I anticipate our findings to inform on the fraction of pervasive transcription engaging in tTI. My proposal promises to advance our understanding of genomes by reconciling how the transcription of variable non-coding DNA sequences can elicit equivalent functions.
Max ERC Funding
1 499 952 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym Q-CEOM
Project Quantum Cavity Electro- and Opto-Mechanics
Researcher (PI) Albert Schliesser
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), PE2, ERC-2014-STG
Summary Nanomechanical oscillators have recently been realised in the quantum regime, by coupling them to a single mode of the electromagnetic field. Platforms using both superconducting microwave circuits and optical cavities have been employed—separately—for this purpose. Based on the PI's extensive contributions to these developments, we propose to explore the intriguing conceptual and experimental prospects of hybrid multimode systems involving microwave, mechanical and optical modes in the quantum regime, thus unifying the fields of quantum cavity optomechanics and electromechanics.
To reach this ambitious goal, an optomechanical system involving two optical modes and one mechanical mode will serve as testbed for quantum conversion and tripartite entanglement protocols. Particular attention will be devoted to the evasion of mechanical thermal noise through noise-resilient schemes, relying, for example, on mechanically dark Bogoliubov modes. This will enable the conservation of quantum coherence in spite of the inevitable coupling of the mechanical device to a thermal environment. The protocols, once established, will be transferred to a hybrid multimode system, consisting of a superconducting microwave resonator, a nanomechanical oscillator, and an optical cavity mode. In this system, we will explore unprecedented opportunities to transduce, entangle and amplify microwave and optical modes through a mechanical device.
The specific implementation proposed here opens new avenues for the ultralow-noise processing of microwave signals, with potential applications in radio astronomy or magnetic resonance imaging. In the quantum sciences, it bears great promise to overcome the dichotomy between superconducting circuit platforms for information processing, and flying optical photons for its communication. More generally, the schemes studied here can serve as a blueprint for mechanical transducers—coupling to spin, charge, and fields alike—in hybrid quantum systems.
Summary
Nanomechanical oscillators have recently been realised in the quantum regime, by coupling them to a single mode of the electromagnetic field. Platforms using both superconducting microwave circuits and optical cavities have been employed—separately—for this purpose. Based on the PI's extensive contributions to these developments, we propose to explore the intriguing conceptual and experimental prospects of hybrid multimode systems involving microwave, mechanical and optical modes in the quantum regime, thus unifying the fields of quantum cavity optomechanics and electromechanics.
To reach this ambitious goal, an optomechanical system involving two optical modes and one mechanical mode will serve as testbed for quantum conversion and tripartite entanglement protocols. Particular attention will be devoted to the evasion of mechanical thermal noise through noise-resilient schemes, relying, for example, on mechanically dark Bogoliubov modes. This will enable the conservation of quantum coherence in spite of the inevitable coupling of the mechanical device to a thermal environment. The protocols, once established, will be transferred to a hybrid multimode system, consisting of a superconducting microwave resonator, a nanomechanical oscillator, and an optical cavity mode. In this system, we will explore unprecedented opportunities to transduce, entangle and amplify microwave and optical modes through a mechanical device.
The specific implementation proposed here opens new avenues for the ultralow-noise processing of microwave signals, with potential applications in radio astronomy or magnetic resonance imaging. In the quantum sciences, it bears great promise to overcome the dichotomy between superconducting circuit platforms for information processing, and flying optical photons for its communication. More generally, the schemes studied here can serve as a blueprint for mechanical transducers—coupling to spin, charge, and fields alike—in hybrid quantum systems.
Max ERC Funding
1 495 073 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
