Project acronym 3DIMAGE
Project 3D Imaging Across Lengthscales: From Atoms to Grains
Researcher (PI) Paul Anthony Midgley
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), PE4, ERC-2011-ADG_20110209
Summary "Understanding structure-property relationships across lengthscales is key to the design of functional and structural materials and devices. Moreover, the complexity of modern devices extends to three dimensions and as such 3D characterization is required across those lengthscales to provide a complete understanding and enable improvement in the material’s physical and chemical behaviour. 3D imaging and analysis from the atomic scale through to granular microstructure is proposed through the development of electron tomography using (S)TEM, and ‘dual beam’ SEM-FIB, techniques offering complementary approaches to 3D imaging across lengthscales stretching over 5 orders of magnitude.
We propose to extend tomography to include novel methods to determine atom positions in 3D with approaches incorporating new reconstruction algorithms, image processing and complementary nano-diffraction techniques. At the nanoscale, true 3D nano-metrology of morphology and composition is a key objective of the project, minimizing reconstruction and visualization artefacts. Mapping strain and optical properties in 3D are ambitious and exciting challenges that will yield new information at the nanoscale. Using the SEM-FIB, 3D ‘mesoscale’ structures will be revealed: morphology, crystallography and composition can be mapped simultaneously, with ~5nm resolution and over volumes too large to tackle by (S)TEM and too small for most x-ray techniques. In parallel, we will apply 3D imaging to a wide variety of key materials including heterogeneous catalysts, aerospace alloys, biomaterials, photovoltaic materials, and novel semiconductors.
We will collaborate with many departments in Cambridge and institutes worldwide. The personnel on the proposal will cover all aspects of the tomography proposed using high-end TEMs, including an aberration-corrected Titan, and a Helios dual beam. Importantly, a postdoc is dedicated to developing new algorithms for reconstruction, image and spectral processing."
Summary
"Understanding structure-property relationships across lengthscales is key to the design of functional and structural materials and devices. Moreover, the complexity of modern devices extends to three dimensions and as such 3D characterization is required across those lengthscales to provide a complete understanding and enable improvement in the material’s physical and chemical behaviour. 3D imaging and analysis from the atomic scale through to granular microstructure is proposed through the development of electron tomography using (S)TEM, and ‘dual beam’ SEM-FIB, techniques offering complementary approaches to 3D imaging across lengthscales stretching over 5 orders of magnitude.
We propose to extend tomography to include novel methods to determine atom positions in 3D with approaches incorporating new reconstruction algorithms, image processing and complementary nano-diffraction techniques. At the nanoscale, true 3D nano-metrology of morphology and composition is a key objective of the project, minimizing reconstruction and visualization artefacts. Mapping strain and optical properties in 3D are ambitious and exciting challenges that will yield new information at the nanoscale. Using the SEM-FIB, 3D ‘mesoscale’ structures will be revealed: morphology, crystallography and composition can be mapped simultaneously, with ~5nm resolution and over volumes too large to tackle by (S)TEM and too small for most x-ray techniques. In parallel, we will apply 3D imaging to a wide variety of key materials including heterogeneous catalysts, aerospace alloys, biomaterials, photovoltaic materials, and novel semiconductors.
We will collaborate with many departments in Cambridge and institutes worldwide. The personnel on the proposal will cover all aspects of the tomography proposed using high-end TEMs, including an aberration-corrected Titan, and a Helios dual beam. Importantly, a postdoc is dedicated to developing new algorithms for reconstruction, image and spectral processing."
Max ERC Funding
2 337 330 €
Duration
Start date: 2012-01-01, End date: 2017-12-31
Project acronym ADSNeSP
Project Active and Driven Systems: Nonequilibrium Statistical Physics
Researcher (PI) Michael Elmhirst CATES
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), PE3, ERC-2016-ADG
Summary Active Matter systems, such as self-propelled colloids, violate time-reversal symmetry by producing entropy locally, typically converting fuel into mechanical motion at the particle scale. Other driven systems instead produce entropy because of global forcing by external fields, or boundary conditions that impose macroscopic fluxes (such as the momentum flux across a fluid sheared between moving parallel walls).
Nonequilibrium statistical physics (NeSP) is the basic toolbox for both classes of system. In recent years, much progress in NeSP has stemmed from bottom-up work on driven systems. This has provided a number of exactly solved benchmark models, and extended approximation techniques to address driven non-ergodic systems, such as sheared glasses. Meanwhile, work on fluctuation theorems and stochastic thermodynamics have created profound, model-independent insights into dynamics far from equilibrium.
More recently, the field of Active Matter has moved forward rapidly, leaving in its wake a series of generic and profound NeSP questions that now need answers: When is time-reversal symmetry, broken at the microscale, restored by coarse-graining? If it is restored, is an effective thermodynamic description is possible? How different is an active system's behaviour from a globally forced one?
ADSNeSP aims to distil from recent Active Matter research such fundamental questions; answer them first in the context of specific models and second in more general terms; and then, using the tools and insights gained, shed new light on longstanding problems in the wider class of driven systems.
I believe these new tools and insights will be substantial, because local activity takes systems far from equilibrium in a conceptually distinct direction from most types of global driving. By focusing on general principles and on simple models of activity, I seek to create a new vantage point that can inform, and potentially transform, wider areas of statistical physics.
Summary
Active Matter systems, such as self-propelled colloids, violate time-reversal symmetry by producing entropy locally, typically converting fuel into mechanical motion at the particle scale. Other driven systems instead produce entropy because of global forcing by external fields, or boundary conditions that impose macroscopic fluxes (such as the momentum flux across a fluid sheared between moving parallel walls).
Nonequilibrium statistical physics (NeSP) is the basic toolbox for both classes of system. In recent years, much progress in NeSP has stemmed from bottom-up work on driven systems. This has provided a number of exactly solved benchmark models, and extended approximation techniques to address driven non-ergodic systems, such as sheared glasses. Meanwhile, work on fluctuation theorems and stochastic thermodynamics have created profound, model-independent insights into dynamics far from equilibrium.
More recently, the field of Active Matter has moved forward rapidly, leaving in its wake a series of generic and profound NeSP questions that now need answers: When is time-reversal symmetry, broken at the microscale, restored by coarse-graining? If it is restored, is an effective thermodynamic description is possible? How different is an active system's behaviour from a globally forced one?
ADSNeSP aims to distil from recent Active Matter research such fundamental questions; answer them first in the context of specific models and second in more general terms; and then, using the tools and insights gained, shed new light on longstanding problems in the wider class of driven systems.
I believe these new tools and insights will be substantial, because local activity takes systems far from equilibrium in a conceptually distinct direction from most types of global driving. By focusing on general principles and on simple models of activity, I seek to create a new vantage point that can inform, and potentially transform, wider areas of statistical physics.
Max ERC Funding
2 043 630 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym AFTERTHEGOLDRUSH
Project Addressing global sustainability challenges by changing perceptions in catalyst design
Researcher (PI) Graham John Hutchings
Host Institution (HI) CARDIFF UNIVERSITY
Call Details Advanced Grant (AdG), PE4, ERC-2011-ADG_20110209
Summary One of the greatest challenges facing society is the sustainability of resources. At present, a step change in the sustainable use of resources is needed and catalysis lies at the heart of the solution by providing new routes to carbon dioxide mitigation, energy security and water conservation. It is clear that new high efficiency game-changing catalysts are required to meet the challenge. This proposal will focus on excellence in catalyst design by learning from recent step change advances in gold catalysis by challenging perceptions. Intense interest in gold catalysts over the past two decades has accelerated our understanding of gold particle-size effects, gold-support and gold-metal interactions, the interchange between atomic and ionic gold species, and the role of the gold-support interface in creating and maintaining catalytic activity. The field has also driven the development of cutting-edge techniques, particularly in microscopy and transient kinetics, providing detailed structural characterisation on the nano-scale and probing the short-range and often short-lived interactions. By comparison, our understanding of other metal catalysts has remained relatively static.
The proposed programme will engender a step change in the design of supported-metal catalysts, by exploiting the learning and the techniques emerging from gold catalysis. The research will be set out in two themes. In Theme 1 two established key grand challenges will be attacked; namely, energy vectors and greenhouse gas control. Theme 2 will address two new and emerging grand challenges in catalysis namely the effective low temperature activation of primary carbon hydrogen bonds and CO2 utilisation where instead of treating CO2 as a thermodynamic endpoint, the aim will be to re-use it as a feedstock for bulk chemical and fuel production. The legacy of the research will be the development of a new catalyst design approach that will provide a tool box for future catalyst development.
Summary
One of the greatest challenges facing society is the sustainability of resources. At present, a step change in the sustainable use of resources is needed and catalysis lies at the heart of the solution by providing new routes to carbon dioxide mitigation, energy security and water conservation. It is clear that new high efficiency game-changing catalysts are required to meet the challenge. This proposal will focus on excellence in catalyst design by learning from recent step change advances in gold catalysis by challenging perceptions. Intense interest in gold catalysts over the past two decades has accelerated our understanding of gold particle-size effects, gold-support and gold-metal interactions, the interchange between atomic and ionic gold species, and the role of the gold-support interface in creating and maintaining catalytic activity. The field has also driven the development of cutting-edge techniques, particularly in microscopy and transient kinetics, providing detailed structural characterisation on the nano-scale and probing the short-range and often short-lived interactions. By comparison, our understanding of other metal catalysts has remained relatively static.
The proposed programme will engender a step change in the design of supported-metal catalysts, by exploiting the learning and the techniques emerging from gold catalysis. The research will be set out in two themes. In Theme 1 two established key grand challenges will be attacked; namely, energy vectors and greenhouse gas control. Theme 2 will address two new and emerging grand challenges in catalysis namely the effective low temperature activation of primary carbon hydrogen bonds and CO2 utilisation where instead of treating CO2 as a thermodynamic endpoint, the aim will be to re-use it as a feedstock for bulk chemical and fuel production. The legacy of the research will be the development of a new catalyst design approach that will provide a tool box for future catalyst development.
Max ERC Funding
2 279 785 €
Duration
Start date: 2012-04-01, End date: 2017-03-31
Project acronym ALEXANDRIA
Project Large-Scale Formal Proof for the Working Mathematician
Researcher (PI) Lawrence PAULSON
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), PE6, ERC-2016-ADG
Summary Mathematical proofs have always been prone to error. Today, proofs can be hundreds of pages long and combine results from many specialisms, making them almost impossible to check. One solution is to deploy modern verification technology. Interactive theorem provers have demonstrated their potential as vehicles for formalising mathematics through achievements such as the verification of the Kepler Conjecture. Proofs done using such tools reach a high standard of correctness.
However, existing theorem provers are unsuitable for mathematics. Their formal proofs are unreadable. They struggle to do simple tasks, such as evaluating limits. They lack much basic mathematics, and the material they do have is difficult to locate and apply.
ALEXANDRIA will create a proof development environment attractive to working mathematicians, utilising the best technology available across computer science. Its focus will be the management and use of large-scale mathematical knowledge, both theorems and algorithms. The project will employ mathematicians to investigate the formalisation of mathematics in practice. Our already substantial formalised libraries will serve as the starting point. They will be extended and annotated to support sophisticated searches. Techniques will be borrowed from machine learning, information retrieval and natural language processing. Algorithms will be treated similarly: ALEXANDRIA will help users find and invoke the proof methods and algorithms appropriate for the task.
ALEXANDRIA will provide (1) comprehensive formal mathematical libraries; (2) search within libraries, and the mining of libraries for proof patterns; (3) automated support for the construction of large formal proofs; (4) sound and practical computer algebra tools.
ALEXANDRIA will be based on legible structured proofs. Formal proofs should be not mere code, but a machine-checkable form of communication between mathematicians.
Summary
Mathematical proofs have always been prone to error. Today, proofs can be hundreds of pages long and combine results from many specialisms, making them almost impossible to check. One solution is to deploy modern verification technology. Interactive theorem provers have demonstrated their potential as vehicles for formalising mathematics through achievements such as the verification of the Kepler Conjecture. Proofs done using such tools reach a high standard of correctness.
However, existing theorem provers are unsuitable for mathematics. Their formal proofs are unreadable. They struggle to do simple tasks, such as evaluating limits. They lack much basic mathematics, and the material they do have is difficult to locate and apply.
ALEXANDRIA will create a proof development environment attractive to working mathematicians, utilising the best technology available across computer science. Its focus will be the management and use of large-scale mathematical knowledge, both theorems and algorithms. The project will employ mathematicians to investigate the formalisation of mathematics in practice. Our already substantial formalised libraries will serve as the starting point. They will be extended and annotated to support sophisticated searches. Techniques will be borrowed from machine learning, information retrieval and natural language processing. Algorithms will be treated similarly: ALEXANDRIA will help users find and invoke the proof methods and algorithms appropriate for the task.
ALEXANDRIA will provide (1) comprehensive formal mathematical libraries; (2) search within libraries, and the mining of libraries for proof patterns; (3) automated support for the construction of large formal proofs; (4) sound and practical computer algebra tools.
ALEXANDRIA will be based on legible structured proofs. Formal proofs should be not mere code, but a machine-checkable form of communication between mathematicians.
Max ERC Funding
2 430 140 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym Arctic Domus
Project Arctic Domestication: Emplacing Human-Animal Relationships in the Circumpolar North
Researcher (PI) David George Anderson
Host Institution (HI) THE UNIVERSITY COURT OF THE UNIVERSITY OF ABERDEEN
Call Details Advanced Grant (AdG), SH2, ERC-2011-ADG_20110406
Summary This 6-year project aims to co-ordinate field research in each of these fields to elaborate a new model of emplaced human-animal relations evoking recent theoretical concerns of the definition of the person, the attribution of agency, and renewed attention to ‘built environments’. The project will work inductively from empirical observations in seven field sites across the circumpolar Arctic from the Russian Federation, to Fennoscandia, to Canada. The circumpolar Arctic originally provided many of the primary thought experiments for classic models of cultural evolution. It has now again become the focus of powerful debates over the balance between the protection of cultural heritage and the development of natural resources to fuel a future for industrial economies. The human-non-human relationships chosen for study cover the full range of theoretical and political discourse within the sciences today from primary encounters in domination to contemporary bio-technical innovations in farming. The team will transcend typical ‘existential’ models of domination between people and animals by describing complex social settings where more than one species interact with the cultural landscape. The team will also challenge existing definitions between wild and tame by instead examining what links these behaviour types together. Further, the team members will examine how domestication was never a sudden, fleeting intuition but rather a process wherein people and domesticates are sometimes closer and sometimes farther from each other. Finally, the research team, working within the above mentioned literatures, will develop a renewed model – a new way of describing – these relationships which does not necessarily rely upon metaphors of domination, competition, individual struggle, origins, or hybridity. The strength of the team, and the principle investigator, is their demonstrated ability to carry out fieldwork in this often difficult to access region.
Summary
This 6-year project aims to co-ordinate field research in each of these fields to elaborate a new model of emplaced human-animal relations evoking recent theoretical concerns of the definition of the person, the attribution of agency, and renewed attention to ‘built environments’. The project will work inductively from empirical observations in seven field sites across the circumpolar Arctic from the Russian Federation, to Fennoscandia, to Canada. The circumpolar Arctic originally provided many of the primary thought experiments for classic models of cultural evolution. It has now again become the focus of powerful debates over the balance between the protection of cultural heritage and the development of natural resources to fuel a future for industrial economies. The human-non-human relationships chosen for study cover the full range of theoretical and political discourse within the sciences today from primary encounters in domination to contemporary bio-technical innovations in farming. The team will transcend typical ‘existential’ models of domination between people and animals by describing complex social settings where more than one species interact with the cultural landscape. The team will also challenge existing definitions between wild and tame by instead examining what links these behaviour types together. Further, the team members will examine how domestication was never a sudden, fleeting intuition but rather a process wherein people and domesticates are sometimes closer and sometimes farther from each other. Finally, the research team, working within the above mentioned literatures, will develop a renewed model – a new way of describing – these relationships which does not necessarily rely upon metaphors of domination, competition, individual struggle, origins, or hybridity. The strength of the team, and the principle investigator, is their demonstrated ability to carry out fieldwork in this often difficult to access region.
Max ERC Funding
2 497 830 €
Duration
Start date: 2012-07-01, End date: 2018-06-30
Project acronym ASAP
Project Adaptive Security and Privacy
Researcher (PI) Bashar Nuseibeh
Host Institution (HI) THE OPEN UNIVERSITY
Call Details Advanced Grant (AdG), PE6, ERC-2011-ADG_20110209
Summary With the prevalence of mobile computing devices and the increasing availability of pervasive services, ubiquitous computing (Ubicomp) is a reality for many people. This reality is generating opportunities for people to interact socially in new and richer ways, and to work more effectively in a variety of new environments. More generally, Ubicomp infrastructures – controlled by software – will determine users’ access to critical services.
With these opportunities come higher risks of misuse by malicious agents. Therefore, the role and design of software for managing use and protecting against misuse is critical, and the engineering of software that is both functionally effective while safe guarding user assets from harm is a key challenge. Indeed the very nature of Ubicomp means that software must adapt to the changing needs of users and their environment, and, more critically, to the different threats to users’ security and privacy.
ASAP proposes to radically re-conceptualise software engineering for Ubicomp in ways that are cognisant of the changing functional needs of users, of the changing threats to user assets, and of the changing relationships between them. We propose to deliver adaptive software capabilities for supporting users in managing their privacy requirements, and adaptive software capabilities to deliver secure software that underpin those requirements. A key novelty of our approach is its holistic treatment of security and human behaviour. To achieve this, it draws upon contributions from requirements engineering, security & privacy engineering, and human-computer interaction. Our aim is to contribute to software engineering that empowers and protects Ubicomp users. Underpinning our approach will be the development of representations of security and privacy problem structures that capture user requirements, the context in which those requirements arise, and the adaptive software that aims to meet those requirements.
Summary
With the prevalence of mobile computing devices and the increasing availability of pervasive services, ubiquitous computing (Ubicomp) is a reality for many people. This reality is generating opportunities for people to interact socially in new and richer ways, and to work more effectively in a variety of new environments. More generally, Ubicomp infrastructures – controlled by software – will determine users’ access to critical services.
With these opportunities come higher risks of misuse by malicious agents. Therefore, the role and design of software for managing use and protecting against misuse is critical, and the engineering of software that is both functionally effective while safe guarding user assets from harm is a key challenge. Indeed the very nature of Ubicomp means that software must adapt to the changing needs of users and their environment, and, more critically, to the different threats to users’ security and privacy.
ASAP proposes to radically re-conceptualise software engineering for Ubicomp in ways that are cognisant of the changing functional needs of users, of the changing threats to user assets, and of the changing relationships between them. We propose to deliver adaptive software capabilities for supporting users in managing their privacy requirements, and adaptive software capabilities to deliver secure software that underpin those requirements. A key novelty of our approach is its holistic treatment of security and human behaviour. To achieve this, it draws upon contributions from requirements engineering, security & privacy engineering, and human-computer interaction. Our aim is to contribute to software engineering that empowers and protects Ubicomp users. Underpinning our approach will be the development of representations of security and privacy problem structures that capture user requirements, the context in which those requirements arise, and the adaptive software that aims to meet those requirements.
Max ERC Funding
2 499 041 €
Duration
Start date: 2012-10-01, End date: 2018-09-30
Project acronym ASTEX
Project Attosecond Science by Transmission and Emission of X-rays
Researcher (PI) Jonathan Philip Marangos
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Advanced Grant (AdG), PE2, ERC-2011-ADG_20110209
Summary "This is a programme of advanced research with potential for high scientific impact and applications to areas of great strategic importance such as renewable energy and biomolecular technology. The aim is to develop and apply a combination of cutting-edge tools to observe and understand dynamics in molecules and condensed phase matter with attosecond temporal and nanometre spatial resolutions. The programme, will exploit two new types of measurements that my group have already begun to develop: high harmonic generation (HHG) spectroscopy and attosecond absorption pump-probe spectroscopy, and will apply them to the measurement of attosecond electron dynamics in large molecules and the condensed phase. These methods rely upon the emission and transmission of soft X-ray attosecond fields that make accessible measurement not only of larger molecules in the gas phase but also thin (micron to nanometre) samples in the condensed phase. This is a research project that will open new frontiers both experimentally and theoretically. The challenge of this research is high and will be met by a concerted programme that is well matched to my teams experimental and theoretical expertise in attosecond physics, ultrafast intense-field science, soft X-ray techniques and advanced techniques for creating gaseous and condensed phase samples."
Summary
"This is a programme of advanced research with potential for high scientific impact and applications to areas of great strategic importance such as renewable energy and biomolecular technology. The aim is to develop and apply a combination of cutting-edge tools to observe and understand dynamics in molecules and condensed phase matter with attosecond temporal and nanometre spatial resolutions. The programme, will exploit two new types of measurements that my group have already begun to develop: high harmonic generation (HHG) spectroscopy and attosecond absorption pump-probe spectroscopy, and will apply them to the measurement of attosecond electron dynamics in large molecules and the condensed phase. These methods rely upon the emission and transmission of soft X-ray attosecond fields that make accessible measurement not only of larger molecules in the gas phase but also thin (micron to nanometre) samples in the condensed phase. This is a research project that will open new frontiers both experimentally and theoretically. The challenge of this research is high and will be met by a concerted programme that is well matched to my teams experimental and theoretical expertise in attosecond physics, ultrafast intense-field science, soft X-ray techniques and advanced techniques for creating gaseous and condensed phase samples."
Max ERC Funding
2 344 390 €
Duration
Start date: 2012-04-01, End date: 2017-03-31
Project acronym Biblant
Project The Bible and Antiquity in the 19th-Century
Researcher (PI) Simon Goldhill
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), SH5, ERC-2011-ADG_20110406
Summary This project will investigate the interface between the study of the bible and the study of antiquity in the nineteenth century. These two areas -- the bible and classics -- are central to the intellectual world of the 19th century, a source of knowledge, contention, and authority both as discrete topics, and, more importantly, in relation to and in competition with one another. It is impossible to understand Victorian society without appreciating the intellectual, social and institutional force of these concerns with the past. Yet modern disciplinary formation has not only separated them in the academy, but also marginalized both subject areas -- which has deeply attenuated comprehension of this foundational era. Our project will bring together scholars working on a range of fields including classics, history of education, cultural history, art history, literary history to bring back into view a fundamental but deeply misunderstood and underexplored aspect of the nineteenth century, which continues to have a significant impact on the contemporary world.
Summary
This project will investigate the interface between the study of the bible and the study of antiquity in the nineteenth century. These two areas -- the bible and classics -- are central to the intellectual world of the 19th century, a source of knowledge, contention, and authority both as discrete topics, and, more importantly, in relation to and in competition with one another. It is impossible to understand Victorian society without appreciating the intellectual, social and institutional force of these concerns with the past. Yet modern disciplinary formation has not only separated them in the academy, but also marginalized both subject areas -- which has deeply attenuated comprehension of this foundational era. Our project will bring together scholars working on a range of fields including classics, history of education, cultural history, art history, literary history to bring back into view a fundamental but deeply misunderstood and underexplored aspect of the nineteenth century, which continues to have a significant impact on the contemporary world.
Max ERC Funding
2 497 046 €
Duration
Start date: 2012-06-01, End date: 2017-05-31
Project acronym BIO-H-BORROW
Project Biocatalytic Amine Synthesis via Hydrogen Borrowing
Researcher (PI) Nicholas TURNER
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Call Details Advanced Grant (AdG), PE5, ERC-2016-ADG
Summary Amine containing compounds are ubiquitous in everyday life and find applications ranging from polymers to pharmaceuticals. The vast majority of amines are synthetic and manufactured on large scale which creates waste as well as requiring high temperatures and pressures. The increasing availability of biocatalysts, together with an understanding of how they can be used in organic synthesis (biocatalytic retrosynthesis), has stimulated chemists to consider new ways of making target molecules. In this context, the iterative construction of C-N bonds via biocatalytic hydrogen borrowing represents a powerful and unexplored way to synthesise a wide range of target amine molecules in an efficient manner. Hydrogen borrowing involves telescoping redox neutral reactions together using only catalytic amounts of hydrogen.
In this project we will engineer the three key target biocatalysts (reductive aminase, amine dehydrogenase, alcohol dehydrogenase) required for biocatalytic hydrogen borrowing such that they possess the required regio-, chemo- and stereo-selectivity for practical application. Recently discovered reductive aminases (RedAms) and amine dehydrogenases (AmDHs) will be engineered for enantioselective coupling of alcohols (1o, 2o) with ammonia/amines (1o, 2o, 3o) under redox neutral conditions. Alcohol dehydrogenases will be engineered for low enantioselectivity. Hydrogen borrowing requires mutually compatible cofactors shared by two enzymes and in some cases will require redesign of cofactor specificity. Thereafter we shall develop conditions for the combined use of these biocatalysts under hydrogen borrowing conditions (catalytic NADH, NADPH), to enable the conversion of simple and sustainable feedstocks (alcohols) into amines using ammonia as the nitrogen source.
The main deliverables of BIO-H-BORROW will be a set of novel engineered biocatalysts together with redox neutral cascades for the synthesis of amine products from inexpensive and renewable precursors.
Summary
Amine containing compounds are ubiquitous in everyday life and find applications ranging from polymers to pharmaceuticals. The vast majority of amines are synthetic and manufactured on large scale which creates waste as well as requiring high temperatures and pressures. The increasing availability of biocatalysts, together with an understanding of how they can be used in organic synthesis (biocatalytic retrosynthesis), has stimulated chemists to consider new ways of making target molecules. In this context, the iterative construction of C-N bonds via biocatalytic hydrogen borrowing represents a powerful and unexplored way to synthesise a wide range of target amine molecules in an efficient manner. Hydrogen borrowing involves telescoping redox neutral reactions together using only catalytic amounts of hydrogen.
In this project we will engineer the three key target biocatalysts (reductive aminase, amine dehydrogenase, alcohol dehydrogenase) required for biocatalytic hydrogen borrowing such that they possess the required regio-, chemo- and stereo-selectivity for practical application. Recently discovered reductive aminases (RedAms) and amine dehydrogenases (AmDHs) will be engineered for enantioselective coupling of alcohols (1o, 2o) with ammonia/amines (1o, 2o, 3o) under redox neutral conditions. Alcohol dehydrogenases will be engineered for low enantioselectivity. Hydrogen borrowing requires mutually compatible cofactors shared by two enzymes and in some cases will require redesign of cofactor specificity. Thereafter we shall develop conditions for the combined use of these biocatalysts under hydrogen borrowing conditions (catalytic NADH, NADPH), to enable the conversion of simple and sustainable feedstocks (alcohols) into amines using ammonia as the nitrogen source.
The main deliverables of BIO-H-BORROW will be a set of novel engineered biocatalysts together with redox neutral cascades for the synthesis of amine products from inexpensive and renewable precursors.
Max ERC Funding
2 337 548 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym BLASTOFF
Project Retooling plant immunity for resistance to blast fungi
Researcher (PI) Sophien KAMOUN
Host Institution (HI) THE SAINSBURY LABORATORY
Call Details Advanced Grant (AdG), LS9, ERC-2016-ADG
Summary Plant NLR-type immune receptors tend to have a narrow spectrum of pathogen recognition, which is currently limiting their value in agriculture. NLRs can recognize pathogen effectors through unconventional domains that have evolved by duplication of an effector target followed by fusion into the NLR. One NLR with an integrated domain is the rice resistance protein Pik-1, which binds an effector of the blast fungus Magnaporthe oryzae via its Heavy-Metal Associated (HMA) domain. We solved the crystal structure of the HMA domain of Pik-1 in complex with a blast fungus effector and gained an unprecedented level of detail of the molecular interactions that define pathogen recognition. This led to the overall aim of this proposal to generate a complete picture of the biophysical interactions between blast fungus effectors and HMA-containing cereal proteins to guide the retooling of the plant immune system towards resistance to blast diseases. M. oryzae is a general cereal killer that infects wheat, barley and rice, which are staple food for a majority of the world population. The central hypothesis of the proposed research is that mutations in cereal HMA-containing proteins will result in broad-spectrum resistance to blast fungi.
To achieve our goal, we will pursue the following objectives:
1. BIOPHYSICS. Define the biophysical properties that underpin binding of M. oryzae effectors to HMA-containing proteins of cereal crops.
2. RECEPTOR ENGINEERING. Develop Pik-1 receptors that respond to a wide-spectrum of M. oryzae effectors.
3. GENOME EDITING. Mutate HMA domain-containing genes in cereal genomes to confer broad-spectrum blast resistance.
At the completion of this project, we will generate a thorough understanding of the biophysical properties of pathogen effector binding to cereal HMA proteins, and deliver traits and non-transgenic cultivars for breeding blast disease resistance in cereal crops.
Summary
Plant NLR-type immune receptors tend to have a narrow spectrum of pathogen recognition, which is currently limiting their value in agriculture. NLRs can recognize pathogen effectors through unconventional domains that have evolved by duplication of an effector target followed by fusion into the NLR. One NLR with an integrated domain is the rice resistance protein Pik-1, which binds an effector of the blast fungus Magnaporthe oryzae via its Heavy-Metal Associated (HMA) domain. We solved the crystal structure of the HMA domain of Pik-1 in complex with a blast fungus effector and gained an unprecedented level of detail of the molecular interactions that define pathogen recognition. This led to the overall aim of this proposal to generate a complete picture of the biophysical interactions between blast fungus effectors and HMA-containing cereal proteins to guide the retooling of the plant immune system towards resistance to blast diseases. M. oryzae is a general cereal killer that infects wheat, barley and rice, which are staple food for a majority of the world population. The central hypothesis of the proposed research is that mutations in cereal HMA-containing proteins will result in broad-spectrum resistance to blast fungi.
To achieve our goal, we will pursue the following objectives:
1. BIOPHYSICS. Define the biophysical properties that underpin binding of M. oryzae effectors to HMA-containing proteins of cereal crops.
2. RECEPTOR ENGINEERING. Develop Pik-1 receptors that respond to a wide-spectrum of M. oryzae effectors.
3. GENOME EDITING. Mutate HMA domain-containing genes in cereal genomes to confer broad-spectrum blast resistance.
At the completion of this project, we will generate a thorough understanding of the biophysical properties of pathogen effector binding to cereal HMA proteins, and deliver traits and non-transgenic cultivars for breeding blast disease resistance in cereal crops.
Max ERC Funding
2 491 893 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
