Project acronym ALPROS
Project Artificial Life-like Processive Systems
Researcher (PI) Roeland Johannes Maria Nolte
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Advanced Grant (AdG), PE5, ERC-2011-ADG_20110209
Summary Toroidal processive enzymes (e.g. enzymes/proteins that are able to thread onto biopolymers and to perform stepwise reactions along the polymer chain) are among the most fascinating tools involved in the clockwork machinery of life. Processive catalysis is ubiquitous in Nature, viz. DNA polymerases, endo- and exo-nucleases and; it plays a crucial role in numerous events of the cell’s life, including most of the replication, transmission, and expression and repair processes of the genetic information. In the case of DNA polymerases the protein catalyst encircles the DNA and whilst moving along it, make copies of high fidelity. Although numerous works have been reported in relation with the synthesis of natural enzymes' analogues, very few efforts have been paid in comparison to mimic these processive properties. It is the goal of this proposal to rectify this oversight and unravel the essential components of Nature’s polymer catalysts. The individual projects are designed to specifically target the essential aspects of processive catalysis, i.e. rate of motion, rate of catalysis, and transfer of information. One project is aimed at extending the research into a processive catalytic system that is more suitable for industrial application. Two projects involve more farsighted studies and are designed to push the research way beyond the current boundaries into the area of Turing machines and bio-rotaxane catalysts which can modify DNA in a non-natural process. The vision of this proposal is to open up the field of ‘processive catalysis’ and invigorate the next generation of chemists to develop information transfer and toroidal processive catalysts. The construction of synthetic analogues of processive enzymes could open a gate toward a large range of applications, ranging from intelligent tailoring of polymers to information storage and processing.
Summary
Toroidal processive enzymes (e.g. enzymes/proteins that are able to thread onto biopolymers and to perform stepwise reactions along the polymer chain) are among the most fascinating tools involved in the clockwork machinery of life. Processive catalysis is ubiquitous in Nature, viz. DNA polymerases, endo- and exo-nucleases and; it plays a crucial role in numerous events of the cell’s life, including most of the replication, transmission, and expression and repair processes of the genetic information. In the case of DNA polymerases the protein catalyst encircles the DNA and whilst moving along it, make copies of high fidelity. Although numerous works have been reported in relation with the synthesis of natural enzymes' analogues, very few efforts have been paid in comparison to mimic these processive properties. It is the goal of this proposal to rectify this oversight and unravel the essential components of Nature’s polymer catalysts. The individual projects are designed to specifically target the essential aspects of processive catalysis, i.e. rate of motion, rate of catalysis, and transfer of information. One project is aimed at extending the research into a processive catalytic system that is more suitable for industrial application. Two projects involve more farsighted studies and are designed to push the research way beyond the current boundaries into the area of Turing machines and bio-rotaxane catalysts which can modify DNA in a non-natural process. The vision of this proposal is to open up the field of ‘processive catalysis’ and invigorate the next generation of chemists to develop information transfer and toroidal processive catalysts. The construction of synthetic analogues of processive enzymes could open a gate toward a large range of applications, ranging from intelligent tailoring of polymers to information storage and processing.
Max ERC Funding
1 603 699 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym ARTISYM
Project Artificial endosymbiosis
Researcher (PI) Jan Van hest
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Call Details Advanced Grant (AdG), PE5, ERC-2015-AdG
Summary Living organisms have acquired new functionalities by uptake and integration of species to create symbiotic life-forms. This process of endosymbiosis has intrigued scientists over the years, albeit mostly from an evolution biology perspective. With the advance of chemical and synthetic biology, our ability to create molecular-life-like systems has increased tremendously, which enables us to build cell and organelle-like structures. However, these advances have not been taken to a level to study comprehensively if endosymbiosis can be applied to non-living systems or to integrate living with non-living matter. The aim of the research described in the ARTISYM proposal is to establish the field of artificial endosymbiosis. Two lines of research will be followed. First, we will incorporate artificial organelles in living cells to design hybrid cells with acquired functionality. This investigation is scientifically of great interest, as it will show us how to introduce novel compartmentalized pathways into living organisms. It also serves an important societal goal, as with these compartments dysfunctional cellular processes can be corrected. We will follow both a transient and a permanent approach. With the transient route biodegradable nanoreactors are introduced to supply living cells temporarily with novel function. Functionality is permanently introduced using genetic engineering to express protein-based nanoreactors in living cells, or via organelle transplantation of healthy mitochondria in diseased living cells. Secondly I aim to create artificial cells with the ability to perform endosymbiosis; the uptake and presence of artificial organelles in synthetic vesicles allows them to dynamically respond to their environment. Responses that are envisaged are shape changes, motility, and growth and division. Furthermore, the incorporation of natural organelles in liposomes provides biocatalytic cascades with the necessary cofactors to function in an artificial cell
Summary
Living organisms have acquired new functionalities by uptake and integration of species to create symbiotic life-forms. This process of endosymbiosis has intrigued scientists over the years, albeit mostly from an evolution biology perspective. With the advance of chemical and synthetic biology, our ability to create molecular-life-like systems has increased tremendously, which enables us to build cell and organelle-like structures. However, these advances have not been taken to a level to study comprehensively if endosymbiosis can be applied to non-living systems or to integrate living with non-living matter. The aim of the research described in the ARTISYM proposal is to establish the field of artificial endosymbiosis. Two lines of research will be followed. First, we will incorporate artificial organelles in living cells to design hybrid cells with acquired functionality. This investigation is scientifically of great interest, as it will show us how to introduce novel compartmentalized pathways into living organisms. It also serves an important societal goal, as with these compartments dysfunctional cellular processes can be corrected. We will follow both a transient and a permanent approach. With the transient route biodegradable nanoreactors are introduced to supply living cells temporarily with novel function. Functionality is permanently introduced using genetic engineering to express protein-based nanoreactors in living cells, or via organelle transplantation of healthy mitochondria in diseased living cells. Secondly I aim to create artificial cells with the ability to perform endosymbiosis; the uptake and presence of artificial organelles in synthetic vesicles allows them to dynamically respond to their environment. Responses that are envisaged are shape changes, motility, and growth and division. Furthermore, the incorporation of natural organelles in liposomes provides biocatalytic cascades with the necessary cofactors to function in an artificial cell
Max ERC Funding
2 500 000 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym BIOMATE
Project Soft Biomade Materials: Modular Protein Polymers and their nano-assemblies
Researcher (PI) Martinus Abraham Cohen Stuart
Host Institution (HI) WAGENINGEN UNIVERSITY
Call Details Advanced Grant (AdG), PE5, ERC-2010-AdG_20100224
Summary From a polymer chemistry perspective, the way in which nature produces its plethora of different proteins is a miracle of precision: the synthesis of each single molecule is directed by the sequence information chemically coded in DNA. The present state of recombinant DNA technology should in principle allow us to make genes that code for entirely new, very sophisticated amino acid polymers, which are chosen and designed by man to serve as new polymer materials. It has been shown that it is indeed possible to make use of the protein biosynthetic machinery and produce such de novo protein polymers, but it is not clear what their potentials are in terms of new materials with desired functionalities.
I propose to develop a new class of protein polymers, chosen such that they form nanostructured materials by triggered folding and multimolecular assembly. The plan is based on three innovative ideas: (i) each new protein polymer will be constructed from a limited set of selected amino acid sequences, called modules (hence the term modular protein polymers) (ii) new, high-yield fermentation strategies will be developed so that polymers will become available in significant quantities for evaluation and application; (iii) the design of modular protein polymers is carried out as a cyclic process in which sequence selection, construction of artificial genes, optimisation of fermentation for high yield, studying polymer folding and assembly, and modelling of the nanostructure by molecular simulation are all logically connected, allowing efficient selection of target sequences.
This project is a cross-road. It brings together biotechnology and polymer science, creating a unique set of biomaterials for medical and pharmaceutical use, that can be easily extended into a manifold of biofunctional materials. Moreover, it will provide us with fresh tools and valuable insights to tackle the subtle relations between protein sequence and folding.
Summary
From a polymer chemistry perspective, the way in which nature produces its plethora of different proteins is a miracle of precision: the synthesis of each single molecule is directed by the sequence information chemically coded in DNA. The present state of recombinant DNA technology should in principle allow us to make genes that code for entirely new, very sophisticated amino acid polymers, which are chosen and designed by man to serve as new polymer materials. It has been shown that it is indeed possible to make use of the protein biosynthetic machinery and produce such de novo protein polymers, but it is not clear what their potentials are in terms of new materials with desired functionalities.
I propose to develop a new class of protein polymers, chosen such that they form nanostructured materials by triggered folding and multimolecular assembly. The plan is based on three innovative ideas: (i) each new protein polymer will be constructed from a limited set of selected amino acid sequences, called modules (hence the term modular protein polymers) (ii) new, high-yield fermentation strategies will be developed so that polymers will become available in significant quantities for evaluation and application; (iii) the design of modular protein polymers is carried out as a cyclic process in which sequence selection, construction of artificial genes, optimisation of fermentation for high yield, studying polymer folding and assembly, and modelling of the nanostructure by molecular simulation are all logically connected, allowing efficient selection of target sequences.
This project is a cross-road. It brings together biotechnology and polymer science, creating a unique set of biomaterials for medical and pharmaceutical use, that can be easily extended into a manifold of biofunctional materials. Moreover, it will provide us with fresh tools and valuable insights to tackle the subtle relations between protein sequence and folding.
Max ERC Funding
2 497 044 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
Project acronym CATCH-22
Project High temperature superconductivity and the Catch-22 conundrum
Researcher (PI) Nigel Hussey
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Advanced Grant (AdG), PE3, ERC-2018-ADG
Summary CATCH-22 sets out to resolve the mystery of the cuprate high temperature superconductors. Hailed as one of the major discoveries of the 20th Century, its central mysteries – the pairing mechanism, the origin of the ‘pseudogap’ and the nature of the ‘strange metal’ phase, have remained elusive for over 30 years. Typically, what scatters electrons also binds them into pairs, and in the cuprates, the strong pairing interaction manifests itself in the strange metal phase as intense scattering, so strong in fact that it drives the electronic states required for pairing incoherent. In other words, what first promotes high temperature superconductivity ultimately destroys it! This logical paradox is the Catch-22 conundrum.
CATCH-22, the program, comprises three parts. Part 1 will explore the fate of electronic states within the strange metal phase by studying how the metallic response diminishes across universal bounds, both as a function of temperature and interaction strength, through momentum-averaged electrical conductivity and thermal diffusivity studies and momentum-resolved photoemission spectroscopy. Part 2 will seek to access the ground state of optimally doped cuprates for the first time, by applying intense current and laser pulses to ultra-thin samples in a high magnetic field. The latter, if successful, will open up a new frontier in which intense THz light and intense magnetic fields combine to access the terra incognita of hidden phases. Finally, Part 3 will explore the origins of the strange metal at the edge of the superconducting dome and search for manifestations of incoherence in other strange metals in an attempt to unify the governing principles. Given that the central mysteries are intertwined – the strange metal is a precursor to the pseudogap which in turn leads to superconductivity - CATCH-22 will aim to bring significant new insight into all three and pave the way, finally, for a coherent phenomenological model for cuprate superconductivity.
Summary
CATCH-22 sets out to resolve the mystery of the cuprate high temperature superconductors. Hailed as one of the major discoveries of the 20th Century, its central mysteries – the pairing mechanism, the origin of the ‘pseudogap’ and the nature of the ‘strange metal’ phase, have remained elusive for over 30 years. Typically, what scatters electrons also binds them into pairs, and in the cuprates, the strong pairing interaction manifests itself in the strange metal phase as intense scattering, so strong in fact that it drives the electronic states required for pairing incoherent. In other words, what first promotes high temperature superconductivity ultimately destroys it! This logical paradox is the Catch-22 conundrum.
CATCH-22, the program, comprises three parts. Part 1 will explore the fate of electronic states within the strange metal phase by studying how the metallic response diminishes across universal bounds, both as a function of temperature and interaction strength, through momentum-averaged electrical conductivity and thermal diffusivity studies and momentum-resolved photoemission spectroscopy. Part 2 will seek to access the ground state of optimally doped cuprates for the first time, by applying intense current and laser pulses to ultra-thin samples in a high magnetic field. The latter, if successful, will open up a new frontier in which intense THz light and intense magnetic fields combine to access the terra incognita of hidden phases. Finally, Part 3 will explore the origins of the strange metal at the edge of the superconducting dome and search for manifestations of incoherence in other strange metals in an attempt to unify the governing principles. Given that the central mysteries are intertwined – the strange metal is a precursor to the pseudogap which in turn leads to superconductivity - CATCH-22 will aim to bring significant new insight into all three and pave the way, finally, for a coherent phenomenological model for cuprate superconductivity.
Max ERC Funding
2 495 629 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym CHEMBIOSPHING
Project Chemical biology of sphingolipids: fundamental studies and clinical applications
Researcher (PI) Herman Steven Overkleeft
Host Institution (HI) UNIVERSITEIT LEIDEN
Call Details Advanced Grant (AdG), PE5, ERC-2011-ADG_20110209
Summary "Sphingolipids are major components of the human cell and are involved in human pathologies ranging from lysosomal storage disorders to type 2 diabetes. Here, we propose to establish an integrated research program for the study of sphingolipid metabolism, in health and disease. We will combine state-of-the-art synthetic organic chemistry, bioorganic chemistry, analytical chemistry, molecular biology and biochemistry techniques and concepts and apply these in an integrated chemical biology approach to study and manipulate sphingolipid metabolism in vivo and in vitro, using human cells and animal models. The program is subdivided in three individual research lines that are interconnected both in terms of technology development and in their biological context. 1) We will develop modified sphinganine derivatives and apply these to study sphingolipid homeostasis in cells derived from healthy and diseased (Gaucher, Fabry, Niemann-Pick A/B disease) individuals/animal models. This question will be addressed in a chemical metabolomics/lipidomics approach. 2) We will develop activity-based probes aimed at monitoring enzyme activity levels of glycosidases involved in (glyco)sphingolipid metabolism, in particular the enzymes that - when mutated and thereby reduced in activity- are responsible for the lysosomal storage disorders Gaucher disease and Fabry disease. 3) We will develop well-defined enzymes and chaperone proteins for directed correction of sphingolipid homeostasis in Gaucher, Fabry and Niemann-Pick A/B patients, via a newly designed semi-synthetic approach that combines sortase-mediated ligation with synthetic chemistry. Deliverables are a better understanding of the composition of the sphingolipid pool that are at the basis of lysosomal storage disorders, effective ways to in situ monitor the efficacy of therapies (enzyme inhibitors, chemical chaperones, recombinant enzymes) to treat these and improved semi-synthetic proteins for enzyme replacement therapy."
Summary
"Sphingolipids are major components of the human cell and are involved in human pathologies ranging from lysosomal storage disorders to type 2 diabetes. Here, we propose to establish an integrated research program for the study of sphingolipid metabolism, in health and disease. We will combine state-of-the-art synthetic organic chemistry, bioorganic chemistry, analytical chemistry, molecular biology and biochemistry techniques and concepts and apply these in an integrated chemical biology approach to study and manipulate sphingolipid metabolism in vivo and in vitro, using human cells and animal models. The program is subdivided in three individual research lines that are interconnected both in terms of technology development and in their biological context. 1) We will develop modified sphinganine derivatives and apply these to study sphingolipid homeostasis in cells derived from healthy and diseased (Gaucher, Fabry, Niemann-Pick A/B disease) individuals/animal models. This question will be addressed in a chemical metabolomics/lipidomics approach. 2) We will develop activity-based probes aimed at monitoring enzyme activity levels of glycosidases involved in (glyco)sphingolipid metabolism, in particular the enzymes that - when mutated and thereby reduced in activity- are responsible for the lysosomal storage disorders Gaucher disease and Fabry disease. 3) We will develop well-defined enzymes and chaperone proteins for directed correction of sphingolipid homeostasis in Gaucher, Fabry and Niemann-Pick A/B patients, via a newly designed semi-synthetic approach that combines sortase-mediated ligation with synthetic chemistry. Deliverables are a better understanding of the composition of the sphingolipid pool that are at the basis of lysosomal storage disorders, effective ways to in situ monitor the efficacy of therapies (enzyme inhibitors, chemical chaperones, recombinant enzymes) to treat these and improved semi-synthetic proteins for enzyme replacement therapy."
Max ERC Funding
2 999 600 €
Duration
Start date: 2012-06-01, End date: 2017-05-31
Project acronym COLMIN
Project A Google Earth Approach to Understanding Collagen Mineralization
Researcher (PI) Nico SOMMERDIJK
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Call Details Advanced Grant (AdG), PE4, ERC-2017-ADG
Summary Collagen mineralization in bone is one of the most crucial processes in our body as it supplies the skeleton on which we depend for support and protection. Bone’s impressive mechanical properties arise from the hierarchical organization of the organic collagen matrix that is mineralized with ultrathin, aligned inorganic crystals of carbonated hydroxyapatite.
Despite its importance to the human body, relatively little is understood about collagen mineralization and how the proteins govern mineral growth with such precision. This is because the matrix development is a complex process with different stages that occur over multiple length scales and depends on many different components.
I propose to obtain the first comprehensive picture of the collagen mineralization mechanism by unraveling its dynamics and structural details. It is not only of great fundamental importance, it also opens the way to the development of better biomaterials, as well as to strategies for the treatment of mineralization-related diseases.
I will achieve this ambitious goal by designing a dedicated tissue engineering platform that models real bone as closely as possible, and will allow application of multiple advanced analysis techniques. These I will employ in a “Google Earth” approach, studying the process from the micrometer to the nanometer scale, combining live cell imaging and “beyond state-of-the-art” electron microscopy with chemical and biochemical analysis to reveal the details of collagen mineralization with the highest spatial, temporal and molecular resolution thus far. Exploiting my extensive expertise in the field of biomineralization and advanced electron microscopy, COLMIN will provide a major step in understanding collagen formation and mineralization, and provide insights that will help to fight bone-related diseases. The advanced multidisciplinary methodology developed here will set a new standard for the advanced analysis of bone formation and other biological processes.
Summary
Collagen mineralization in bone is one of the most crucial processes in our body as it supplies the skeleton on which we depend for support and protection. Bone’s impressive mechanical properties arise from the hierarchical organization of the organic collagen matrix that is mineralized with ultrathin, aligned inorganic crystals of carbonated hydroxyapatite.
Despite its importance to the human body, relatively little is understood about collagen mineralization and how the proteins govern mineral growth with such precision. This is because the matrix development is a complex process with different stages that occur over multiple length scales and depends on many different components.
I propose to obtain the first comprehensive picture of the collagen mineralization mechanism by unraveling its dynamics and structural details. It is not only of great fundamental importance, it also opens the way to the development of better biomaterials, as well as to strategies for the treatment of mineralization-related diseases.
I will achieve this ambitious goal by designing a dedicated tissue engineering platform that models real bone as closely as possible, and will allow application of multiple advanced analysis techniques. These I will employ in a “Google Earth” approach, studying the process from the micrometer to the nanometer scale, combining live cell imaging and “beyond state-of-the-art” electron microscopy with chemical and biochemical analysis to reveal the details of collagen mineralization with the highest spatial, temporal and molecular resolution thus far. Exploiting my extensive expertise in the field of biomineralization and advanced electron microscopy, COLMIN will provide a major step in understanding collagen formation and mineralization, and provide insights that will help to fight bone-related diseases. The advanced multidisciplinary methodology developed here will set a new standard for the advanced analysis of bone formation and other biological processes.
Max ERC Funding
3 498 006 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym COLUMNARCODECRACKING
Project Cracking the columnar-level code in the visual hierarchy: Ultra high-field functional MRI, neuro-cognitive modelling and high-resolution brain-computer interfaces
Researcher (PI) Rainer Goebel
Host Institution (HI) UNIVERSITEIT MAASTRICHT
Call Details Advanced Grant (AdG), SH4, ERC-2010-AdG_20100407
Summary "Recent developments of high-field functional magnetic resonance imaging (fMRI) have advanced the level of functional detail to sub-millimetre spatial resolution. This is of critical importance because in the mammalian cortex, small functional cortical patches appear to constitute fundamental units of brain function. These functional units are often organized as ""cortical columns"" that contain clusters of neurons with similar functional preferences. The present project will investigate what ""features"" are coded by functional “columnar-level” units in the visual cortex, how represented entities can be decoded from distributed activity patterns, and how modelled intra- and inter-areal connections between feature representations enable neuro-cognitive computations. The research of this project strives towards a new level of insight in the functional organization of the human brain: Instead of describing observed fMRI activity at the level of specialized brain areas, the focus will be shifted towards the content coded within brain regions. The project investigates columnar-level coding in three cross-fertilising sub-projects. In the first sub-project, sophisticated experimental designs, ultra high-field fMRI and advanced data analyses will be combined to unravel columnar-level feature representations and the entities represented by distributed patterns at different levels of the visual hierarchy. In the second sub-project, a large-scale neural network model will be developed with the major goal to integrate measured columnar-level representations in a new theory of invariant object recognition and visual attention. In the third sub-project, high-resolution Brain Computer Interfaces (hr-BCIs) will be created that are based on information extracted from columnar-level representations. The hr-BCIs will implement highly content-specific neurofeedback tools for therapeutic treatment, and advanced communication devices for patients with severe motor impairments."
Summary
"Recent developments of high-field functional magnetic resonance imaging (fMRI) have advanced the level of functional detail to sub-millimetre spatial resolution. This is of critical importance because in the mammalian cortex, small functional cortical patches appear to constitute fundamental units of brain function. These functional units are often organized as ""cortical columns"" that contain clusters of neurons with similar functional preferences. The present project will investigate what ""features"" are coded by functional “columnar-level” units in the visual cortex, how represented entities can be decoded from distributed activity patterns, and how modelled intra- and inter-areal connections between feature representations enable neuro-cognitive computations. The research of this project strives towards a new level of insight in the functional organization of the human brain: Instead of describing observed fMRI activity at the level of specialized brain areas, the focus will be shifted towards the content coded within brain regions. The project investigates columnar-level coding in three cross-fertilising sub-projects. In the first sub-project, sophisticated experimental designs, ultra high-field fMRI and advanced data analyses will be combined to unravel columnar-level feature representations and the entities represented by distributed patterns at different levels of the visual hierarchy. In the second sub-project, a large-scale neural network model will be developed with the major goal to integrate measured columnar-level representations in a new theory of invariant object recognition and visual attention. In the third sub-project, high-resolution Brain Computer Interfaces (hr-BCIs) will be created that are based on information extracted from columnar-level representations. The hr-BCIs will implement highly content-specific neurofeedback tools for therapeutic treatment, and advanced communication devices for patients with severe motor impairments."
Max ERC Funding
2 473 381 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
Project acronym COMP-MICR-CROW-MEM
Project Computational Microscopy of Crowded Membranes
Researcher (PI) Siewert Jan Marrink
Host Institution (HI) RIJKSUNIVERSITEIT GRONINGEN
Call Details Advanced Grant (AdG), PE4, ERC-2014-ADG
Summary Cell membranes form a highly complex and heterogeneous mixture of membrane proteins and lipids. Understanding the protein-lipid interplay that gives rise to the lateral organisation principles of cell membranes is essential for life and health. Thus, investigations of these crowded membranes is emerging as a new and exceptionally exciting frontier at the crossroads of biology, life sciences, physics, and chemistry.
However, our current understanding of the detailed organisation of cellular membranes remains rather elusive. Characterisation of the structural heterogeneity in-vivo remains very challenging, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins with the required spatio-temporal resolution. In recent years, computer simulations have become a unique investigatory tool for understanding the driving forces governing the lateral organisation of cellular membrane components and this “computational microscopy” has become indispensible as a complement to traditional microscopy methods.
In this ERC project I will, using advanced computational microscopy, study the interaction of lipids and proteins in complex, crowded, membrane patches, to enable the driving forces of membrane protein sorting and clustering to be unravelled at conditions closely mimicking real cellular membranes. The specific objectives are:
• To develop a novel computational microscopy framework for simulating biomolecular processes at multiple resolutions.
• To use this new computational microscopy framework to investigate the driving forces of membrane protein sorting and clustering.
• To provide a molecular view of realistic, crowded, biological membranes composed of hundreds of different lipids and proteins.
The outcomes will enable subsequent studies of many different types of cell membranes based on forthcoming lipidomics studies and progress in structural characterisation of membrane proteins.
Summary
Cell membranes form a highly complex and heterogeneous mixture of membrane proteins and lipids. Understanding the protein-lipid interplay that gives rise to the lateral organisation principles of cell membranes is essential for life and health. Thus, investigations of these crowded membranes is emerging as a new and exceptionally exciting frontier at the crossroads of biology, life sciences, physics, and chemistry.
However, our current understanding of the detailed organisation of cellular membranes remains rather elusive. Characterisation of the structural heterogeneity in-vivo remains very challenging, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins with the required spatio-temporal resolution. In recent years, computer simulations have become a unique investigatory tool for understanding the driving forces governing the lateral organisation of cellular membrane components and this “computational microscopy” has become indispensible as a complement to traditional microscopy methods.
In this ERC project I will, using advanced computational microscopy, study the interaction of lipids and proteins in complex, crowded, membrane patches, to enable the driving forces of membrane protein sorting and clustering to be unravelled at conditions closely mimicking real cellular membranes. The specific objectives are:
• To develop a novel computational microscopy framework for simulating biomolecular processes at multiple resolutions.
• To use this new computational microscopy framework to investigate the driving forces of membrane protein sorting and clustering.
• To provide a molecular view of realistic, crowded, biological membranes composed of hundreds of different lipids and proteins.
The outcomes will enable subsequent studies of many different types of cell membranes based on forthcoming lipidomics studies and progress in structural characterisation of membrane proteins.
Max ERC Funding
2 396 585 €
Duration
Start date: 2015-11-01, End date: 2020-10-31
Project acronym CONSTANS
Project Control of the Structure of Light at the Nanoscale
Researcher (PI) Laurens Kuipers
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Advanced Grant (AdG), PE3, ERC-2013-ADG
Summary In the last decade, the fields of nanoplasmonics and photonic crystals have opened up the nanoscale for optical control. Both the flow and emission of light can be controlled at these small length scales, giving rise to new science and applications. Interestingly, freely propagating light beams can already contain nanoscale features, i.e. optical singularities. Little is known about this nanoscale structure of light.
I propose to (1) reveal the structure of light at the nanoscale and its interaction with geometrical structures or other light structures; and (2) achieve full spatio-temporal control of the nanoscale structure of light. Crucial to achieving these goals are technological innovations, which will be crosscutting objectives. These include the first nonlinear vectorial scanning near-field microscope and novel near-field probes allowing access to new combinations of vector fields.
This next step in the field of nano-optics is possible due to recent breakthroughs in the control and visualization of light at the nanoscale obtained in my group. I will combine newly acquired access to the vectorial nature of light with its active control to investigate how (deep-) subwavelength structures of light of different frequencies affect each other when coupled through a nonlinear interaction in a nanostructured material. In parallel I will focus on optical singularities. Because of their extreme size, small changes in their position will lead to huge effects in the local light fields, opening up potential for all-optical and therefore ultrafast control.
The research will lead to innovations in the visualization and control of light at the nanoscale, access to the magnetic component of light, nanoscale nonlinear optics and coherent control of light fields. The knowledge gain will be crucial for applications like ultrasensitive biosensors based on superchiral light, ultrafast magneto-optics and nanoscale quantum optics.
Summary
In the last decade, the fields of nanoplasmonics and photonic crystals have opened up the nanoscale for optical control. Both the flow and emission of light can be controlled at these small length scales, giving rise to new science and applications. Interestingly, freely propagating light beams can already contain nanoscale features, i.e. optical singularities. Little is known about this nanoscale structure of light.
I propose to (1) reveal the structure of light at the nanoscale and its interaction with geometrical structures or other light structures; and (2) achieve full spatio-temporal control of the nanoscale structure of light. Crucial to achieving these goals are technological innovations, which will be crosscutting objectives. These include the first nonlinear vectorial scanning near-field microscope and novel near-field probes allowing access to new combinations of vector fields.
This next step in the field of nano-optics is possible due to recent breakthroughs in the control and visualization of light at the nanoscale obtained in my group. I will combine newly acquired access to the vectorial nature of light with its active control to investigate how (deep-) subwavelength structures of light of different frequencies affect each other when coupled through a nonlinear interaction in a nanostructured material. In parallel I will focus on optical singularities. Because of their extreme size, small changes in their position will lead to huge effects in the local light fields, opening up potential for all-optical and therefore ultrafast control.
The research will lead to innovations in the visualization and control of light at the nanoscale, access to the magnetic component of light, nanoscale nonlinear optics and coherent control of light fields. The knowledge gain will be crucial for applications like ultrasensitive biosensors based on superchiral light, ultrafast magneto-optics and nanoscale quantum optics.
Max ERC Funding
2 493 600 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym CONTACTS
Project Traces of contact: Language contact studies and historical linguistics
Researcher (PI) Pieter Muysken
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Advanced Grant (AdG), SH5, ERC-2008-AdG
Summary This project aims to establish criteria by which results from language contact studies can be used to strengthen the field of historical linguistics. It does so by applying the scenario model for language contact studies to a number of concrete settings, which differ widely in their level of aggregation and dime depth: the languages of the Amazonian fringe in South America, the complex multilingual setting of the Republic of Suriname, the multilingual interaction of immigrant groups in the Netherlands, and two groups of multilingual individuals. New methods from structural phylogenetics are employed, and the same linguistic variables (TMA and evidentiality marking, argument realization) will be studied in the various projects. In the various projects, use will be made from a shared questionnaire, so that comparable data can be gathered. By applying the scenaio model at various levels of aggregation, a more principled link between language contact studies and historical linguistics can be established.
Summary
This project aims to establish criteria by which results from language contact studies can be used to strengthen the field of historical linguistics. It does so by applying the scenario model for language contact studies to a number of concrete settings, which differ widely in their level of aggregation and dime depth: the languages of the Amazonian fringe in South America, the complex multilingual setting of the Republic of Suriname, the multilingual interaction of immigrant groups in the Netherlands, and two groups of multilingual individuals. New methods from structural phylogenetics are employed, and the same linguistic variables (TMA and evidentiality marking, argument realization) will be studied in the various projects. In the various projects, use will be made from a shared questionnaire, so that comparable data can be gathered. By applying the scenaio model at various levels of aggregation, a more principled link between language contact studies and historical linguistics can be established.
Max ERC Funding
2 499 950 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
