Project acronym 0MSPIN
Project Spintronics based on relativistic phenomena in systems with zero magnetic moment
Researcher (PI) Tomáš Jungwirth
Host Institution (HI) FYZIKALNI USTAV AV CR V.V.I
Call Details Advanced Grant (AdG), PE3, ERC-2010-AdG_20100224
Summary The 0MSPIN project consists of an extensive integrated theoretical, experimental and device development programme of research opening a radical new approach to spintronics. Spintronics has the potential to supersede existing storage and memory applications, and to provide alternatives to current CMOS technology. Ferromagnetic matels used in all current spintronics applications may make it impractical to realise the full potential of spintronics. Metals are unsuitable for transistor and information processing applications, for opto-electronics, or for high-density integration. The 0MSPIN project aims to remove the major road-block holding back the development of spintronics in a radical way: removing the ferromagnetic component from key active parts or from the whole of the spintronic devices. This approach is based on exploiting the combination of exchange and spin-orbit coupling phenomena and material systems with zero macroscopic moment. The goal of the 0MSPIN is to provide a new paradigm by which spintronics can enter the realms of conventional semiconductors in both fundamental condensed matter research and in information technologies. In the central part of the proposal, the research towards this goal is embedded within a materials science project whose aim is to introduce into physics and microelectronics an entirely new class of semiconductors. 0MSPIN seeks to exploit three classes of material systems: (1) Antiferromagnetic bi-metallic 3d-5d alloys (e.g. Mn2Au). (2) Antiferromagnetic I-II-V semiconductors (e.g. LiMnAs). (3) Non-magnetic spin-orbit coupled semiconductors with injected spin-polarized currents (e.g. 2D III-V structures). Proof of concept devices operating at high temperatures will be fabricated to show-case new functionalities offered by zero-moment systems for sensing and memory applications, information processing, and opto-electronics technologies.
Summary
The 0MSPIN project consists of an extensive integrated theoretical, experimental and device development programme of research opening a radical new approach to spintronics. Spintronics has the potential to supersede existing storage and memory applications, and to provide alternatives to current CMOS technology. Ferromagnetic matels used in all current spintronics applications may make it impractical to realise the full potential of spintronics. Metals are unsuitable for transistor and information processing applications, for opto-electronics, or for high-density integration. The 0MSPIN project aims to remove the major road-block holding back the development of spintronics in a radical way: removing the ferromagnetic component from key active parts or from the whole of the spintronic devices. This approach is based on exploiting the combination of exchange and spin-orbit coupling phenomena and material systems with zero macroscopic moment. The goal of the 0MSPIN is to provide a new paradigm by which spintronics can enter the realms of conventional semiconductors in both fundamental condensed matter research and in information technologies. In the central part of the proposal, the research towards this goal is embedded within a materials science project whose aim is to introduce into physics and microelectronics an entirely new class of semiconductors. 0MSPIN seeks to exploit three classes of material systems: (1) Antiferromagnetic bi-metallic 3d-5d alloys (e.g. Mn2Au). (2) Antiferromagnetic I-II-V semiconductors (e.g. LiMnAs). (3) Non-magnetic spin-orbit coupled semiconductors with injected spin-polarized currents (e.g. 2D III-V structures). Proof of concept devices operating at high temperatures will be fabricated to show-case new functionalities offered by zero-moment systems for sensing and memory applications, information processing, and opto-electronics technologies.
Max ERC Funding
1 938 000 €
Duration
Start date: 2011-06-01, End date: 2016-05-31
Project acronym 1stProposal
Project An alternative development of analytic number theory and applications
Researcher (PI) ANDREW Granville
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Advanced Grant (AdG), PE1, ERC-2014-ADG
Summary The traditional (Riemann) approach to analytic number theory uses the zeros of zeta functions. This requires the associated multiplicative function, say f(n), to have special enough properties that the associated Dirichlet series may be analytically continued. In this proposal we continue to develop an approach which requires less of the multiplicative function, linking the original question with the mean value of f. Such techniques have been around for a long time but have generally been regarded as “ad hoc”. In this project we aim to show that one can develop a coherent approach to the whole subject, not only reproving all of the old results, but also many new ones that appear inaccessible to traditional methods.
Our first goal is to complete a monograph yielding a reworking of all the classical theory using these new methods and then to push forward in new directions. The most important is to extend these techniques to GL(n) L-functions, which we hope will now be feasible having found the correct framework in which to proceed. Since we rarely know how to analytically continue such L-functions this could be of great benefit to the subject.
We are developing the large sieve so that it can be used for individual moduli, and will determine a strong form of that. Also a new method to give asymptotics for mean values, when they are not too small.
We wish to incorporate techniques of analytic number theory into our theory, for example recent advances on mean values of Dirichlet polynomials. Also the recent breakthroughs on the sieve suggest strong links that need further exploration.
Additive combinatorics yields important results in many areas. There are strong analogies between its results, and those for multiplicative functions, especially in large value spectrum theory, and its applications. We hope to develop these further.
Much of this is joint work with K Soundararajan of Stanford University.
Summary
The traditional (Riemann) approach to analytic number theory uses the zeros of zeta functions. This requires the associated multiplicative function, say f(n), to have special enough properties that the associated Dirichlet series may be analytically continued. In this proposal we continue to develop an approach which requires less of the multiplicative function, linking the original question with the mean value of f. Such techniques have been around for a long time but have generally been regarded as “ad hoc”. In this project we aim to show that one can develop a coherent approach to the whole subject, not only reproving all of the old results, but also many new ones that appear inaccessible to traditional methods.
Our first goal is to complete a monograph yielding a reworking of all the classical theory using these new methods and then to push forward in new directions. The most important is to extend these techniques to GL(n) L-functions, which we hope will now be feasible having found the correct framework in which to proceed. Since we rarely know how to analytically continue such L-functions this could be of great benefit to the subject.
We are developing the large sieve so that it can be used for individual moduli, and will determine a strong form of that. Also a new method to give asymptotics for mean values, when they are not too small.
We wish to incorporate techniques of analytic number theory into our theory, for example recent advances on mean values of Dirichlet polynomials. Also the recent breakthroughs on the sieve suggest strong links that need further exploration.
Additive combinatorics yields important results in many areas. There are strong analogies between its results, and those for multiplicative functions, especially in large value spectrum theory, and its applications. We hope to develop these further.
Much of this is joint work with K Soundararajan of Stanford University.
Max ERC Funding
2 011 742 €
Duration
Start date: 2015-08-01, End date: 2020-07-31
Project acronym 4PI-SKY
Project 4 pi sky: Extreme Astrophysics with Revolutionary Radio Telescopes
Researcher (PI) Robert Philip Fender
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), PE9, ERC-2010-AdG_20100224
Summary Extreme astrophysical events such as relativistic flows, cataclysmic explosions and black hole accretion are one of the key areas for astrophysics in the 21st century. The extremes of physics experienced in these environments are beyond anything achievable in any laboratory on Earth, and provide a unique glimpse at the laws of physics operating in extraordinary regimes. All of these events are associated with transient radio emission, a tracer both of the acceleration of particles to relativistic energies, and coherent emitting regions with huge effective temperatures. By studying radio bursts from these phenomena we can pinpoint the sources of explosive events, understand the budget of kinetic feedback by explosive events in the ambient medium, and probe the physical state of the universe back to the epoch of reionisation, less than a billion years after the big bang. In seeking to push back the frontiers of extreme astrophysics, I will use a trio of revolutionary new radio telescopes, LOFAR, ASKAP and MeerKAT, pathfinders for the Square Kilometre Array, and all facilities in which I have a major role in the search for transients. I will build an infrastructure which transforms their combined operations for the discovery, classification and reporting of transient astrophysical events, over the whole sky, making them much more than the sum of their parts. This will include development of environments for the coordinated handling of extreme astrophysical events, in real time, via automated systems, as well as novel techniques for the detection of these events in a sea of noise. I will furthermore augment this program by buying in as a major partner to a rapid-response robotic optical telescope, and by cementing my relationship with an orbiting X-ray facility. This multiwavelength dimension will secure the astrophysical interpretation of our observational results and help to revolutionise high-energy astrophysics via a strong scientific exploitation program.
Summary
Extreme astrophysical events such as relativistic flows, cataclysmic explosions and black hole accretion are one of the key areas for astrophysics in the 21st century. The extremes of physics experienced in these environments are beyond anything achievable in any laboratory on Earth, and provide a unique glimpse at the laws of physics operating in extraordinary regimes. All of these events are associated with transient radio emission, a tracer both of the acceleration of particles to relativistic energies, and coherent emitting regions with huge effective temperatures. By studying radio bursts from these phenomena we can pinpoint the sources of explosive events, understand the budget of kinetic feedback by explosive events in the ambient medium, and probe the physical state of the universe back to the epoch of reionisation, less than a billion years after the big bang. In seeking to push back the frontiers of extreme astrophysics, I will use a trio of revolutionary new radio telescopes, LOFAR, ASKAP and MeerKAT, pathfinders for the Square Kilometre Array, and all facilities in which I have a major role in the search for transients. I will build an infrastructure which transforms their combined operations for the discovery, classification and reporting of transient astrophysical events, over the whole sky, making them much more than the sum of their parts. This will include development of environments for the coordinated handling of extreme astrophysical events, in real time, via automated systems, as well as novel techniques for the detection of these events in a sea of noise. I will furthermore augment this program by buying in as a major partner to a rapid-response robotic optical telescope, and by cementing my relationship with an orbiting X-ray facility. This multiwavelength dimension will secure the astrophysical interpretation of our observational results and help to revolutionise high-energy astrophysics via a strong scientific exploitation program.
Max ERC Funding
2 999 847 €
Duration
Start date: 2011-07-01, End date: 2017-06-30
Project acronym ABLASE
Project Advanced Bioderived and Biocompatible Lasers
Researcher (PI) Malte Christian Gather
Host Institution (HI) THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS
Call Details Starting Grant (StG), PE3, ERC-2014-STG
Summary Naturally occurring optical phenomena attract great attention and transform our ability to study biological processes, with “the discovery and development of the green fluorescent protein (GFP)” (Nobel Prize in Chemistry 2008) being a particularly successful example. Although found only in very few species in nature, most organisms can be genetically programmed to produce the brightly fluorescent GFP molecules. Combined with modern fluorescence detection schemes, this has led to entirely new ways of monitoring biological processes. The applicant now demonstrated a biological laser – a completely novel, living source of coherent light based on a single biological cell bioengineered to produce GFP. Such a laser is intrinsically biocompatible, thus offering unique properties not shared by any existing laser. However, the physical processes involved in lasing from GFP remain poorly understood and so far biological lasers rely on bulky, impractical external resonators for optical feedback. Within this project, the applicant and his team will develop for the first time an understanding of stimulated emission in GFP and related proteins and create an unprecedented stand-alone single-cell biolaser based on intracellular optical feedback. These lasers will be deployed as microscopic and biocompatible imaging probes, thus opening in vivo microscopy to dense wavelength-multiplexing and enabling unmatched sensing of biomolecules and mechanical pressure. The evolutionarily evolved nano-structure of GFP will also enable novel ways of studying strong light-matter coupling and will bio-inspire advances of synthetic emitters. The proposed project is inter-disciplinary by its very nature, bridging photonics, genetic engineering and material science. The applicant’s previous pioneering work and synergies with work on other lasers developed at the applicant’s host institution provide an exclusive competitive edge. ERC support would transform this into a truly novel field of research.
Summary
Naturally occurring optical phenomena attract great attention and transform our ability to study biological processes, with “the discovery and development of the green fluorescent protein (GFP)” (Nobel Prize in Chemistry 2008) being a particularly successful example. Although found only in very few species in nature, most organisms can be genetically programmed to produce the brightly fluorescent GFP molecules. Combined with modern fluorescence detection schemes, this has led to entirely new ways of monitoring biological processes. The applicant now demonstrated a biological laser – a completely novel, living source of coherent light based on a single biological cell bioengineered to produce GFP. Such a laser is intrinsically biocompatible, thus offering unique properties not shared by any existing laser. However, the physical processes involved in lasing from GFP remain poorly understood and so far biological lasers rely on bulky, impractical external resonators for optical feedback. Within this project, the applicant and his team will develop for the first time an understanding of stimulated emission in GFP and related proteins and create an unprecedented stand-alone single-cell biolaser based on intracellular optical feedback. These lasers will be deployed as microscopic and biocompatible imaging probes, thus opening in vivo microscopy to dense wavelength-multiplexing and enabling unmatched sensing of biomolecules and mechanical pressure. The evolutionarily evolved nano-structure of GFP will also enable novel ways of studying strong light-matter coupling and will bio-inspire advances of synthetic emitters. The proposed project is inter-disciplinary by its very nature, bridging photonics, genetic engineering and material science. The applicant’s previous pioneering work and synergies with work on other lasers developed at the applicant’s host institution provide an exclusive competitive edge. ERC support would transform this into a truly novel field of research.
Max ERC Funding
1 499 875 €
Duration
Start date: 2015-06-01, End date: 2020-05-31
Project acronym ACCI
Project Atmospheric Chemistry-Climate Interactions
Researcher (PI) John Adrian Pyle
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), PE10, ERC-2010-AdG_20100224
Summary Global change involves a large number of complex interactions between various earth system processes. In the atmosphere, one component of the earth system, there are crucial feedbacks between physical, chemical and biological processes. Thus many of the drivers of climate change depend on chemical processes in the atmosphere including, in addition to ozone and water vapour, methane, nitrous oxide, the halocarbons as well as a range of inorganic and organic aerosols. The link between chemistry and climate is two-way and changes in climate can influence atmospheric chemistry processes in a variety of ways.
Previous studies have looked at these interactions in isolation but the time is now right for more comprehensive studies. The crucial contribution that will be made here is in improving our understanding of the processes within this complex system. Process understanding has been the hallmark of my previous work. The earth system scope here will be ambitiously wide but with a similar drive to understand fundamental processes.
The ambitious programme of research is built around four interrelated questions using new state-of-the-art modelling tools: How will the composition of the stratosphere change in the future, given changes in the concentrations of ozone depleting substances and greenhouse gases? How will these changes in the stratosphere affect tropospheric composition and climate? How will the composition of the troposphere change in the future, given changes in the emissions of ozone precursors and greenhouse gases? How will these changes in the troposphere affect the troposphere-stratosphere climate system?
ACCI will break new ground in bringing all of these questions into a single modelling and diagnostic framework, enabling interrelated questions to be answered which should radically improve our overall projections for global change.
Summary
Global change involves a large number of complex interactions between various earth system processes. In the atmosphere, one component of the earth system, there are crucial feedbacks between physical, chemical and biological processes. Thus many of the drivers of climate change depend on chemical processes in the atmosphere including, in addition to ozone and water vapour, methane, nitrous oxide, the halocarbons as well as a range of inorganic and organic aerosols. The link between chemistry and climate is two-way and changes in climate can influence atmospheric chemistry processes in a variety of ways.
Previous studies have looked at these interactions in isolation but the time is now right for more comprehensive studies. The crucial contribution that will be made here is in improving our understanding of the processes within this complex system. Process understanding has been the hallmark of my previous work. The earth system scope here will be ambitiously wide but with a similar drive to understand fundamental processes.
The ambitious programme of research is built around four interrelated questions using new state-of-the-art modelling tools: How will the composition of the stratosphere change in the future, given changes in the concentrations of ozone depleting substances and greenhouse gases? How will these changes in the stratosphere affect tropospheric composition and climate? How will the composition of the troposphere change in the future, given changes in the emissions of ozone precursors and greenhouse gases? How will these changes in the troposphere affect the troposphere-stratosphere climate system?
ACCI will break new ground in bringing all of these questions into a single modelling and diagnostic framework, enabling interrelated questions to be answered which should radically improve our overall projections for global change.
Max ERC Funding
2 496 926 €
Duration
Start date: 2011-05-01, End date: 2017-04-30
Project acronym ACCORD
Project Algorithms for Complex Collective Decisions on Structured Domains
Researcher (PI) Edith Elkind
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Starting Grant (StG), PE6, ERC-2014-STG
Summary Algorithms for Complex Collective Decisions on Structured Domains.
The aim of this proposal is to substantially advance the field of Computational Social Choice, by developing new tools and methodologies that can be used for making complex group decisions in rich and structured environments. We consider settings where each member of a decision-making body has preferences over a finite set of alternatives, and the goal is to synthesise a collective preference over these alternatives, which may take the form of a partial order over the set of alternatives with a predefined structure: examples include selecting a fixed-size set of alternatives, a ranking of the alternatives, a winner and up to two runner-ups, etc. We will formulate desiderata that apply to such preference aggregation procedures, design specific procedures that satisfy as many of these desiderata as possible, and develop efficient algorithms for computing them. As the latter step may be infeasible on general preference domains, we will focus on identifying the least restrictive domains that enable efficient computation, and use real-life preference data to verify whether the associated restrictions are likely to be satisfied in realistic preference aggregation scenarios. Also, we will determine whether our preference aggregation procedures are computationally resistant to malicious behavior. To lower the cognitive burden on the decision-makers, we will extend our procedures to accept partial rankings as inputs. Finally, to further contribute towards bridging the gap between theory and practice of collective decision making, we will provide open-source software implementations of our procedures, and reach out to the potential users to obtain feedback on their practical applicability.
Summary
Algorithms for Complex Collective Decisions on Structured Domains.
The aim of this proposal is to substantially advance the field of Computational Social Choice, by developing new tools and methodologies that can be used for making complex group decisions in rich and structured environments. We consider settings where each member of a decision-making body has preferences over a finite set of alternatives, and the goal is to synthesise a collective preference over these alternatives, which may take the form of a partial order over the set of alternatives with a predefined structure: examples include selecting a fixed-size set of alternatives, a ranking of the alternatives, a winner and up to two runner-ups, etc. We will formulate desiderata that apply to such preference aggregation procedures, design specific procedures that satisfy as many of these desiderata as possible, and develop efficient algorithms for computing them. As the latter step may be infeasible on general preference domains, we will focus on identifying the least restrictive domains that enable efficient computation, and use real-life preference data to verify whether the associated restrictions are likely to be satisfied in realistic preference aggregation scenarios. Also, we will determine whether our preference aggregation procedures are computationally resistant to malicious behavior. To lower the cognitive burden on the decision-makers, we will extend our procedures to accept partial rankings as inputs. Finally, to further contribute towards bridging the gap between theory and practice of collective decision making, we will provide open-source software implementations of our procedures, and reach out to the potential users to obtain feedback on their practical applicability.
Max ERC Funding
1 395 933 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym ACHILLES-HEEL
Project Crop resistance improvement by mining natural and induced variation in host accessibility factors
Researcher (PI) Sebastian Schornack
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS9, ERC-2014-STG
Summary Increasing crop yield to feed the world is a grand challenge of the 21st century but it is hampered by diseases caused by filamentous plant pathogens. The arms race between pathogen and plant demands constant adjustment of crop germplasm to tackle emerging pathogen races with new virulence features. To date, most crop disease resistance has relied on specific resistance genes that are effective only against a subset of races. We cannot solely rely on classical resistance genes to keep ahead of the pathogens. There is an urgent need to develop approaches based on knowledge of the pathogen’s Achilles heel: core plant processes that are required for pathogen colonization.
Our hypothesis is that disease resistance based on manipulation of host accessibility processes has a higher probability for durability, and is best identified using a broad host-range pathogen. I will employ the filamentous pathogen Phytophthora palmivora to mine plant alleles and unravel host processes providing microbial access in roots and leaves of monocot and dicot plants.
In Aim 1 I will utilize plant symbiosis mutants and allelic variation to elucidate general mechanisms of colonization by filamentous microbes. Importantly, allelic variation will be studied in economically relevant barley and wheat to allow immediate translation into breeding programs.
In Aim 2 I will perform a comparative study of microbial colonization in monocot and dicot roots and leaves. Transcriptional profiling of pathogen and plant will highlight common and contrasting principles and illustrate the impact of differential plant anatomies.
We will challenge our findings by testing beneficial fungi to assess commonalities and differences between mutualist and pathogen colonization. We will use genetics, cell biology and genomics to find suitable resistance alleles highly relevant to crop production and global food security. At the completion of the project, I expect to have a set of genes for resistance breeding.
Summary
Increasing crop yield to feed the world is a grand challenge of the 21st century but it is hampered by diseases caused by filamentous plant pathogens. The arms race between pathogen and plant demands constant adjustment of crop germplasm to tackle emerging pathogen races with new virulence features. To date, most crop disease resistance has relied on specific resistance genes that are effective only against a subset of races. We cannot solely rely on classical resistance genes to keep ahead of the pathogens. There is an urgent need to develop approaches based on knowledge of the pathogen’s Achilles heel: core plant processes that are required for pathogen colonization.
Our hypothesis is that disease resistance based on manipulation of host accessibility processes has a higher probability for durability, and is best identified using a broad host-range pathogen. I will employ the filamentous pathogen Phytophthora palmivora to mine plant alleles and unravel host processes providing microbial access in roots and leaves of monocot and dicot plants.
In Aim 1 I will utilize plant symbiosis mutants and allelic variation to elucidate general mechanisms of colonization by filamentous microbes. Importantly, allelic variation will be studied in economically relevant barley and wheat to allow immediate translation into breeding programs.
In Aim 2 I will perform a comparative study of microbial colonization in monocot and dicot roots and leaves. Transcriptional profiling of pathogen and plant will highlight common and contrasting principles and illustrate the impact of differential plant anatomies.
We will challenge our findings by testing beneficial fungi to assess commonalities and differences between mutualist and pathogen colonization. We will use genetics, cell biology and genomics to find suitable resistance alleles highly relevant to crop production and global food security. At the completion of the project, I expect to have a set of genes for resistance breeding.
Max ERC Funding
1 991 054 €
Duration
Start date: 2015-09-01, End date: 2021-08-31
Project acronym ACMO
Project Systematic dissection of molecular machines and neural circuits coordinating C. elegans aggregation behaviour
Researcher (PI) Mario De Bono
Host Institution (HI) MEDICAL RESEARCH COUNCIL
Call Details Advanced Grant (AdG), LS5, ERC-2010-AdG_20100317
Summary Elucidating how neural circuits coordinate behaviour, and how molecules underpin the properties of individual neurons are major goals of neuroscience. Optogenetics and neural imaging combined with the powerful genetics and well-described nervous system of C. elegans offer special opportunities to address these questions. Previously, we identified a series of sensory neurons that modulate aggregation of C. elegans. These include neurons that respond to O2, CO2, noxious cues, satiety state, and pheromones. We propose to take our analysis to the next level by dissecting how, in mechanistic molecular terms, these distributed inputs modify the activity of populations of interneurons and motoneurons to coordinate group formation. Our strategy is to develop new, highly parallel approaches to replace the traditional piecemeal analysis.
We propose to:
1) Harness next generation sequencing (NGS) to forward genetics, rapidly to identify a molecular ¿parts list¿ for aggregation. Much of the genetics has been done: we have identified almost 200 mutations that inhibit or enhance aggregation but otherwise show no overt phenotype. A pilot study of 50 of these mutations suggests they identify dozens of genes not previously implicated in aggregation. NGS will allow us to molecularly identify these genes in a few months, providing multiple entry points to study molecular and circuitry mechanisms for behaviour.
2) Develop new methods to image the activity of populations of neurons in immobilized and freely moving animals, using genetically encoded indicators such as the calcium sensor cameleon and the voltage indicator mermaid.
This will be the first time a complex behaviour has been dissected in this way. We expect to identify novel conserved molecular and circuitry mechanisms.
Summary
Elucidating how neural circuits coordinate behaviour, and how molecules underpin the properties of individual neurons are major goals of neuroscience. Optogenetics and neural imaging combined with the powerful genetics and well-described nervous system of C. elegans offer special opportunities to address these questions. Previously, we identified a series of sensory neurons that modulate aggregation of C. elegans. These include neurons that respond to O2, CO2, noxious cues, satiety state, and pheromones. We propose to take our analysis to the next level by dissecting how, in mechanistic molecular terms, these distributed inputs modify the activity of populations of interneurons and motoneurons to coordinate group formation. Our strategy is to develop new, highly parallel approaches to replace the traditional piecemeal analysis.
We propose to:
1) Harness next generation sequencing (NGS) to forward genetics, rapidly to identify a molecular ¿parts list¿ for aggregation. Much of the genetics has been done: we have identified almost 200 mutations that inhibit or enhance aggregation but otherwise show no overt phenotype. A pilot study of 50 of these mutations suggests they identify dozens of genes not previously implicated in aggregation. NGS will allow us to molecularly identify these genes in a few months, providing multiple entry points to study molecular and circuitry mechanisms for behaviour.
2) Develop new methods to image the activity of populations of neurons in immobilized and freely moving animals, using genetically encoded indicators such as the calcium sensor cameleon and the voltage indicator mermaid.
This will be the first time a complex behaviour has been dissected in this way. We expect to identify novel conserved molecular and circuitry mechanisms.
Max ERC Funding
2 439 996 €
Duration
Start date: 2011-04-01, End date: 2017-03-31
Project acronym ACTINONSRF
Project MAL: an actin-regulated SRF transcriptional coactivator
Researcher (PI) Richard Treisman
Host Institution (HI) THE FRANCIS CRICK INSTITUTE LIMITED
Call Details Advanced Grant (AdG), LS1, ERC-2010-AdG_20100317
Summary MAL: an actin-regulated SRF transcriptional coactivator
Recent years have seen a revitalised interest in the role of actin in nuclear processes, but the molecular mechanisms involved remain largely unexplored. We will elucidate the molecular basis for the actin-based control of the SRF transcriptional coactivator, MAL. SRF controls transcription through two families of coactivators, the actin-binding MRTFs (MAL, Mkl2), which couple its activity to cytoskeletal dynamics, and the ERK-regulated TCFs (Elk-1, SAP-1, Net). MAL subcellular localisation and transcriptional activity responds to signal-induced changes in G-actin concentration, which are sensed by its actin-binding N-terminal RPEL domain. Members of a second family of RPEL proteins, the Phactrs, also exhibit actin-regulated nucleocytoplasmic shuttling. The proposal addresses the following novel features of actin biology:
¿ Actin as a transcriptional regulator
¿ Actin as a signalling molecule
¿ Actin-binding proteins as targets for regulation by actin, rather than regulators of actin function
We will analyse the sequences and proteins involved in actin-regulated nucleocytoplasmic shuttling, using structural biology and biochemistry to analyse its control by changes in actin-RPEL domain interactions. We will characterise the dynamics of shuttling, and develop reporters for changes in actin-MAL interaction for analysis of pathway activation in vivo. We will identify genes controlling MAL itself, and the balance between the nuclear and cytoplasmic actin pools. The mechanism by which actin represses transcriptional activation by MAL in the nucleus, and its relation to MAL phosphorylation, will be elucidated. Finally, we will map MRTF and TCF cofactor recruitment to SRF targets on a genome-wide scale, and identify the steps in transcription controlled by actin-MAL interaction.
Summary
MAL: an actin-regulated SRF transcriptional coactivator
Recent years have seen a revitalised interest in the role of actin in nuclear processes, but the molecular mechanisms involved remain largely unexplored. We will elucidate the molecular basis for the actin-based control of the SRF transcriptional coactivator, MAL. SRF controls transcription through two families of coactivators, the actin-binding MRTFs (MAL, Mkl2), which couple its activity to cytoskeletal dynamics, and the ERK-regulated TCFs (Elk-1, SAP-1, Net). MAL subcellular localisation and transcriptional activity responds to signal-induced changes in G-actin concentration, which are sensed by its actin-binding N-terminal RPEL domain. Members of a second family of RPEL proteins, the Phactrs, also exhibit actin-regulated nucleocytoplasmic shuttling. The proposal addresses the following novel features of actin biology:
¿ Actin as a transcriptional regulator
¿ Actin as a signalling molecule
¿ Actin-binding proteins as targets for regulation by actin, rather than regulators of actin function
We will analyse the sequences and proteins involved in actin-regulated nucleocytoplasmic shuttling, using structural biology and biochemistry to analyse its control by changes in actin-RPEL domain interactions. We will characterise the dynamics of shuttling, and develop reporters for changes in actin-MAL interaction for analysis of pathway activation in vivo. We will identify genes controlling MAL itself, and the balance between the nuclear and cytoplasmic actin pools. The mechanism by which actin represses transcriptional activation by MAL in the nucleus, and its relation to MAL phosphorylation, will be elucidated. Finally, we will map MRTF and TCF cofactor recruitment to SRF targets on a genome-wide scale, and identify the steps in transcription controlled by actin-MAL interaction.
Max ERC Funding
1 889 995 €
Duration
Start date: 2011-10-01, End date: 2017-09-30
Project acronym ACTOMYOSIN RING
Project Understanding Cytokinetic Actomyosin Ring Assembly Through Genetic Code Expansion, Click Chemistry, DNA origami, and in vitro Reconstitution
Researcher (PI) Mohan Balasubramanian
Host Institution (HI) THE UNIVERSITY OF WARWICK
Call Details Advanced Grant (AdG), LS3, ERC-2014-ADG
Summary The mechanism of cell division is conserved in many eukaryotes, from yeast to man. A contractile ring of filamentous actin and myosin II motors generates the force to bisect a mother cell into two daughters. The actomyosin ring is among the most complex cellular machines, comprising over 150 proteins. Understanding how these proteins organize themselves into a functional ring with appropriate contractile properties remains one of the great challenges in cell biology. Efforts to generate a comprehensive understanding of the mechanism of actomyosin ring assembly have been hampered by the lack of structural information on the arrangement of actin, myosin II, and actin modulators in the ring in its native state. Fundamental questions such as how actin filaments are assembled and organized into a ring remain actively debated. This project will investigate key issues pertaining to cytokinesis in the fission yeast Schizosaccharomyces pombe, which divides employing an actomyosin based contractile ring, using the methods of genetics, biochemistry, cellular imaging, DNA origami, genetic code expansion, and click chemistry. Specifically, we will (1) attempt to visualize actin filament assembly in live cells expressing fluorescent actin generated through synthetic biological approaches, including genetic code expansion and click chemistry (2) decipher actin filament polarity in the actomyosin ring using total internal reflection fluorescence microscopy of labelled dimeric and multimeric myosins V and VI generated through DNA origami approaches (3) address when, where, and how actin filaments for cytokinesis are assembled and organized into a ring and (4) reconstitute actin filament and functional actomyosin ring assembly in permeabilized spheroplasts and in supported bilayers. Success in the project will provide major insight into the mechanism of actomyosin ring assembly and illuminate principles behind cytoskeletal self-organization.
Summary
The mechanism of cell division is conserved in many eukaryotes, from yeast to man. A contractile ring of filamentous actin and myosin II motors generates the force to bisect a mother cell into two daughters. The actomyosin ring is among the most complex cellular machines, comprising over 150 proteins. Understanding how these proteins organize themselves into a functional ring with appropriate contractile properties remains one of the great challenges in cell biology. Efforts to generate a comprehensive understanding of the mechanism of actomyosin ring assembly have been hampered by the lack of structural information on the arrangement of actin, myosin II, and actin modulators in the ring in its native state. Fundamental questions such as how actin filaments are assembled and organized into a ring remain actively debated. This project will investigate key issues pertaining to cytokinesis in the fission yeast Schizosaccharomyces pombe, which divides employing an actomyosin based contractile ring, using the methods of genetics, biochemistry, cellular imaging, DNA origami, genetic code expansion, and click chemistry. Specifically, we will (1) attempt to visualize actin filament assembly in live cells expressing fluorescent actin generated through synthetic biological approaches, including genetic code expansion and click chemistry (2) decipher actin filament polarity in the actomyosin ring using total internal reflection fluorescence microscopy of labelled dimeric and multimeric myosins V and VI generated through DNA origami approaches (3) address when, where, and how actin filaments for cytokinesis are assembled and organized into a ring and (4) reconstitute actin filament and functional actomyosin ring assembly in permeabilized spheroplasts and in supported bilayers. Success in the project will provide major insight into the mechanism of actomyosin ring assembly and illuminate principles behind cytoskeletal self-organization.
Max ERC Funding
2 863 705 €
Duration
Start date: 2015-11-01, End date: 2020-10-31