Project acronym AIME
Project An Inquiry into Modes of Existence
Researcher (PI) Bruno Latour
Host Institution (HI) FONDATION NATIONALE DES SCIENCES POLITIQUES
Call Details Advanced Grant (AdG), SH2, ERC-2010-AdG_20100407
Summary "AIME is an inquiry to make more precise what is lumped together into the confusing word ""modernization"". The work done in the field of science studies (STS) on the progress and practice of science and technology has had the consequence of deeply modifying the definition of ""modernity"", resulting into the provocative idea that ""we (meaning the Europeans) have never been modern"". This is, however only a negative definition. To obtain a positive rendering of the European current situation, it is necessary to start an inquiry in the complex and conflicting set of values that have been invented. This inquiry is possible only if there is a clear and shareable way to judge the differences in the set of truth-conditions that make up those conflicting sets of values. AIME offers a grammar of those differences based on the key notion of modes of existence. Then it builds a procedure and an instrument to test this grammar into a selected set of situations where the definitions of the differing modes of existence is redefined and renegotiated. The result is a set of shareable definitions of what modernization has been in practice. This is important just at the moment when Europe has lost its privileged status and needs to be able to present itself in a new ways to the other cultures and civilizations which are making up the world of globalization with very different views on what it is to modernize themselves."
Summary
"AIME is an inquiry to make more precise what is lumped together into the confusing word ""modernization"". The work done in the field of science studies (STS) on the progress and practice of science and technology has had the consequence of deeply modifying the definition of ""modernity"", resulting into the provocative idea that ""we (meaning the Europeans) have never been modern"". This is, however only a negative definition. To obtain a positive rendering of the European current situation, it is necessary to start an inquiry in the complex and conflicting set of values that have been invented. This inquiry is possible only if there is a clear and shareable way to judge the differences in the set of truth-conditions that make up those conflicting sets of values. AIME offers a grammar of those differences based on the key notion of modes of existence. Then it builds a procedure and an instrument to test this grammar into a selected set of situations where the definitions of the differing modes of existence is redefined and renegotiated. The result is a set of shareable definitions of what modernization has been in practice. This is important just at the moment when Europe has lost its privileged status and needs to be able to present itself in a new ways to the other cultures and civilizations which are making up the world of globalization with very different views on what it is to modernize themselves."
Max ERC Funding
1 334 720 €
Duration
Start date: 2011-09-01, End date: 2015-06-30
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 ARPEMA
Project Anionic redox processes: A transformational approach for advanced energy materials
Researcher (PI) Jean-Marie Tarascon
Host Institution (HI) COLLEGE DE FRANCE
Call Details Advanced Grant (AdG), PE5, ERC-2014-ADG
Summary Redox chemistry provides the fundamental basis for numerous energy-related electrochemical devices, among which Li-ion batteries (LIB) have become the premier energy storage technology for portable electronics and vehicle electrification. Throughout its history, LIB technology has relied on cationic redox reactions as the sole source of energy storage capacity. This is no longer true. In 2013 we demonstrated that Li-driven reversible formation of (O2)n peroxo-groups in new layered oxides led to extraordinary increases in energy storage capacity. This finding, which is receiving worldwide attention, represents a transformational approach for creating advanced energy materials for not only energy storage, but also water splitting applications as both involve peroxo species. However, as is often the case with new discoveries, the fundamental science at work needs to be rationalized and understood. Specifically, what are the mechanisms for ion and electron transport in these Li-driven anionic redox reactions?
To address these seminal questions and to widen the spectrum of materials (transition metal and anion) showing anionic redox chemistry, we propose a comprehensive research program that combines experimental and computational methods. The experimental methods include structural and electrochemical analyses (both ex-situ and in-situ), and computational modeling will be based on first-principles DFT for identifying the fundamental processes that enable anionic redox activity. The knowledge gained from these studies, in combination with our expertise in inorganic synthesis, will enable us to design a new generation of Li-ion battery materials that exhibit substantial increases (20 -30%) in energy storage capacity, with additional impacts on the development of Na-ion batteries and the design of water splitting catalysts, with the feasibility to surpass current water splitting efficiencies via novel (O2)n-based electrocatalysts.
Summary
Redox chemistry provides the fundamental basis for numerous energy-related electrochemical devices, among which Li-ion batteries (LIB) have become the premier energy storage technology for portable electronics and vehicle electrification. Throughout its history, LIB technology has relied on cationic redox reactions as the sole source of energy storage capacity. This is no longer true. In 2013 we demonstrated that Li-driven reversible formation of (O2)n peroxo-groups in new layered oxides led to extraordinary increases in energy storage capacity. This finding, which is receiving worldwide attention, represents a transformational approach for creating advanced energy materials for not only energy storage, but also water splitting applications as both involve peroxo species. However, as is often the case with new discoveries, the fundamental science at work needs to be rationalized and understood. Specifically, what are the mechanisms for ion and electron transport in these Li-driven anionic redox reactions?
To address these seminal questions and to widen the spectrum of materials (transition metal and anion) showing anionic redox chemistry, we propose a comprehensive research program that combines experimental and computational methods. The experimental methods include structural and electrochemical analyses (both ex-situ and in-situ), and computational modeling will be based on first-principles DFT for identifying the fundamental processes that enable anionic redox activity. The knowledge gained from these studies, in combination with our expertise in inorganic synthesis, will enable us to design a new generation of Li-ion battery materials that exhibit substantial increases (20 -30%) in energy storage capacity, with additional impacts on the development of Na-ion batteries and the design of water splitting catalysts, with the feasibility to surpass current water splitting efficiencies via novel (O2)n-based electrocatalysts.
Max ERC Funding
2 249 196 €
Duration
Start date: 2015-10-01, End date: 2020-09-30
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 AUTHORITARIANGLOBAL
Project Authoritarianism in a Global Age: Controlling Information and Communication, Association and People Movement
Researcher (PI) Marlies Glasius
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Advanced Grant (AdG), SH2, ERC-2012-ADG_20120411
Summary The overarching research question of this project is: how is authoritarian rule affected by and responding to globalisation of (a) information and communication, (b) association, and (c) people movement? The wholly unpredicted series of revolts that recently spread across the Arab world suggests that the nature and sustainability of contemporary authoritarian rule are not well-understood. Openness to global ICT and media, international NGOs, and inflow and outflow of people have thrown up new challenges for authoritarian rulers in terms of how to control citizens. This project investigates changes in both the nature and the sustainability of authoritarian rule in relation to the erosion of decision-making autonomy at the state level posited by globalisation theorists.
In four sub-projects, this project will investigate:
1. Whether, how and to what extent globalisation of information and communication, association, and people movement affect authoritarian persistence (longitudinal quantitative study, 1970-2011)
2. How, i.e. with what policy mechanisms, authoritarian states respond to globalisation of information and communication, association, and people movement (qualitative multi-sited studies relating to Belarus, China, Iran and Zimbabwe)
3. How to understand the phenomenon of subnational authoritarianism in its engagement with the democratic state and the wider world in relation to information and communication, association, and people movement (mixed method subnational studies of states within India and Mexico)
4. What authoritarianism is in a global age: reconsidering authoritarianism’s defining characteristics of low accountability and high coercion, and whether these still relate exclusively to statehood (theory study)
The project will transcend the theoretical and empirical separation between globalisation studies (which have neglected authoritarian contexts) and authoritarianism studies(which have taken relatively little notice of effects of globalisation)
Summary
The overarching research question of this project is: how is authoritarian rule affected by and responding to globalisation of (a) information and communication, (b) association, and (c) people movement? The wholly unpredicted series of revolts that recently spread across the Arab world suggests that the nature and sustainability of contemporary authoritarian rule are not well-understood. Openness to global ICT and media, international NGOs, and inflow and outflow of people have thrown up new challenges for authoritarian rulers in terms of how to control citizens. This project investigates changes in both the nature and the sustainability of authoritarian rule in relation to the erosion of decision-making autonomy at the state level posited by globalisation theorists.
In four sub-projects, this project will investigate:
1. Whether, how and to what extent globalisation of information and communication, association, and people movement affect authoritarian persistence (longitudinal quantitative study, 1970-2011)
2. How, i.e. with what policy mechanisms, authoritarian states respond to globalisation of information and communication, association, and people movement (qualitative multi-sited studies relating to Belarus, China, Iran and Zimbabwe)
3. How to understand the phenomenon of subnational authoritarianism in its engagement with the democratic state and the wider world in relation to information and communication, association, and people movement (mixed method subnational studies of states within India and Mexico)
4. What authoritarianism is in a global age: reconsidering authoritarianism’s defining characteristics of low accountability and high coercion, and whether these still relate exclusively to statehood (theory study)
The project will transcend the theoretical and empirical separation between globalisation studies (which have neglected authoritarian contexts) and authoritarianism studies(which have taken relatively little notice of effects of globalisation)
Max ERC Funding
2 451 179 €
Duration
Start date: 2013-10-01, End date: 2019-02-28
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 BIOSPACE
Project Monitoring Biodiversity from Space
Researcher (PI) Andrew Kerr Skidmore
Host Institution (HI) UNIVERSITEIT TWENTE
Call Details Advanced Grant (AdG), SH2, ERC-2018-ADG
Summary Life, with all its diversity, is in crisis. As humans increasingly encroach on biologically complex semi- natural landscapes, no organism, place or ecological function remains unaffected. While all 196 parties (195 countries plus the European Union) to the UN Convention on Biodiversity (CBD) have agreed to monitor the state of biodiversity, the currently available methods to do so leave much to be desired. Traditional monitoring involves the field observation of species by trained specialists, aided by skilled volunteers, whose expertise is restricted to specific biotic groupings. In a process that is both time consuming and inconsistent across time and space, botanists identify and record the presence of plant species and ornithologists the bird biota, resulting in 'unpopular' biotic groups such as fungi, bacteria and insects being under-observed or escaping identification altogether. In this project, a fundamentally different approach to terrestrial biodiversity monitoring couples next generation satellite remote sensing with environmental DNA (eDNA) profiling, complemented where available by legacy human-observed datasets. Satellite remote sensing is able to survey the environment as a single, continuous, fine-resolution map, while eDNA profiling can rapidly quantify much greater taxonomical and functional breadth and depth than human field observation. This project combines, for the first time, these two powerful, cutting-edge techniques for monitoring biodiversity at the global level in a consistent manner. Following from this, another key innovation will be the deepening of our scientific understanding of how biodiversity is impacted by anthropogenic pressure as well as by natural environmental gradients. In concert, these scientific developments will enable the accurate and fine grain monitoring of biodiversity from space – a ground-breaking contribution to the quest to meet the UN Sustainable Development Goals and CBD Aichi targets.
Summary
Life, with all its diversity, is in crisis. As humans increasingly encroach on biologically complex semi- natural landscapes, no organism, place or ecological function remains unaffected. While all 196 parties (195 countries plus the European Union) to the UN Convention on Biodiversity (CBD) have agreed to monitor the state of biodiversity, the currently available methods to do so leave much to be desired. Traditional monitoring involves the field observation of species by trained specialists, aided by skilled volunteers, whose expertise is restricted to specific biotic groupings. In a process that is both time consuming and inconsistent across time and space, botanists identify and record the presence of plant species and ornithologists the bird biota, resulting in 'unpopular' biotic groups such as fungi, bacteria and insects being under-observed or escaping identification altogether. In this project, a fundamentally different approach to terrestrial biodiversity monitoring couples next generation satellite remote sensing with environmental DNA (eDNA) profiling, complemented where available by legacy human-observed datasets. Satellite remote sensing is able to survey the environment as a single, continuous, fine-resolution map, while eDNA profiling can rapidly quantify much greater taxonomical and functional breadth and depth than human field observation. This project combines, for the first time, these two powerful, cutting-edge techniques for monitoring biodiversity at the global level in a consistent manner. Following from this, another key innovation will be the deepening of our scientific understanding of how biodiversity is impacted by anthropogenic pressure as well as by natural environmental gradients. In concert, these scientific developments will enable the accurate and fine grain monitoring of biodiversity from space – a ground-breaking contribution to the quest to meet the UN Sustainable Development Goals and CBD Aichi targets.
Max ERC Funding
2 470 315 €
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 chemech
Project From Chemical Bond Forces and Breakage to Macroscopic Fracture of Soft Materials
Researcher (PI) Costantino CRETON
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Advanced Grant (AdG), PE5, ERC-2015-AdG
Summary Soft materials are irreplaceable in engineering applications where large reversible deformations are needed, and in life sciences to mimic ever more closely or replace a variety of living tissues. While mechanical strength may not be essential for all applications, excessive brittleness is a strong limitation. Yet predicting if a soft material will be tough or brittle from its molecular composition or structure relies on empirical concepts due to the lack of proper tools to detect the damage occurring to the material before it breaks. Taking advantage of the recent advances in materials science and mechanochemistry, we propose a ground-breaking method to investigate the mechanisms of fracture of tough soft materials. To achieve this objective we will use a series of model materials containing a variable population of internal sacrificial bonds that break before the material fails macroscopically, and use a combination of advanced characterization techniques and molecular probes to map stress, strain, bond breakage and structure in a region ~100 µm in size ahead of the propagating crack. By using mechanoluminescent and mechanophore molecules incorporated in the model material in selected positions, confocal laser microscopy, digital image correlation and small-angle X-ray scattering we will gain an unprecedented molecular understanding of where and when bonds break as the material fails and the crack propagates, and will then be able to establish a direct relation between the architecture of soft polymer networks and their fracture energy, leading to a new molecular and multi-scale vision of macroscopic fracture of soft materials. Such advances will be invaluable to guide materials chemists to design and develop better and more finely tuned soft but tough and sometimes self-healing materials to replace living tissues (in bio engineering) and make lightweight tough and flexible parts for energy efficient transport.
Summary
Soft materials are irreplaceable in engineering applications where large reversible deformations are needed, and in life sciences to mimic ever more closely or replace a variety of living tissues. While mechanical strength may not be essential for all applications, excessive brittleness is a strong limitation. Yet predicting if a soft material will be tough or brittle from its molecular composition or structure relies on empirical concepts due to the lack of proper tools to detect the damage occurring to the material before it breaks. Taking advantage of the recent advances in materials science and mechanochemistry, we propose a ground-breaking method to investigate the mechanisms of fracture of tough soft materials. To achieve this objective we will use a series of model materials containing a variable population of internal sacrificial bonds that break before the material fails macroscopically, and use a combination of advanced characterization techniques and molecular probes to map stress, strain, bond breakage and structure in a region ~100 µm in size ahead of the propagating crack. By using mechanoluminescent and mechanophore molecules incorporated in the model material in selected positions, confocal laser microscopy, digital image correlation and small-angle X-ray scattering we will gain an unprecedented molecular understanding of where and when bonds break as the material fails and the crack propagates, and will then be able to establish a direct relation between the architecture of soft polymer networks and their fracture energy, leading to a new molecular and multi-scale vision of macroscopic fracture of soft materials. Such advances will be invaluable to guide materials chemists to design and develop better and more finely tuned soft but tough and sometimes self-healing materials to replace living tissues (in bio engineering) and make lightweight tough and flexible parts for energy efficient transport.
Max ERC Funding
2 251 026 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym ChemicalYouth
Project What chemicals do for youths in their everyday lives
Researcher (PI) Anita Petra Hardon
Host Institution (HI) UNIVERSITEIT VAN AMSTERDAM
Call Details Advanced Grant (AdG), SH2, ERC-2012-ADG_20120411
Summary The everyday lives of contemporary youths are awash with chemicals and pharmaceutical compounds to boost pleasure, moods, sexual performance, vitality, appearance and health. Nevertheless, most studies of chemical use among young people have focused on the abuse of specific recreational drugs and their role within deviant youth sub-cultures. Instead of explaining drug abuse with the purpose of controlling it, this project aims to examine the pervasive use of chemicals from the perspectives of youths themselves. It aims to understand what chemical and pharmaceutical substances, and not only illicit narcotics, ‘do’ for youths. How are chemicals a part of their everyday lives? What role do they play in calming their fears or in achieving their dreams and aspirations? How can we understand the ways in which chemicals affect their bodies and minds?
The theoretical innovation promised by this project lies in its combining of disciplines – most notably medical anthropology, science and technology studies and youth studies – to formulate a new groundbreaking framework for understanding the complex sociality of chemicals in youths’ everyday lives. The framework will have both scientific and societal impact.
Ethnographic research will be conducted in four medium-sized cities: Marseille in France, Amsterdam in the Netherlands, Makassar in Indonesia, and Batangas in the Philippines.
Summary
The everyday lives of contemporary youths are awash with chemicals and pharmaceutical compounds to boost pleasure, moods, sexual performance, vitality, appearance and health. Nevertheless, most studies of chemical use among young people have focused on the abuse of specific recreational drugs and their role within deviant youth sub-cultures. Instead of explaining drug abuse with the purpose of controlling it, this project aims to examine the pervasive use of chemicals from the perspectives of youths themselves. It aims to understand what chemical and pharmaceutical substances, and not only illicit narcotics, ‘do’ for youths. How are chemicals a part of their everyday lives? What role do they play in calming their fears or in achieving their dreams and aspirations? How can we understand the ways in which chemicals affect their bodies and minds?
The theoretical innovation promised by this project lies in its combining of disciplines – most notably medical anthropology, science and technology studies and youth studies – to formulate a new groundbreaking framework for understanding the complex sociality of chemicals in youths’ everyday lives. The framework will have both scientific and societal impact.
Ethnographic research will be conducted in four medium-sized cities: Marseille in France, Amsterdam in the Netherlands, Makassar in Indonesia, and Batangas in the Philippines.
Max ERC Funding
2 489 967 €
Duration
Start date: 2013-06-01, End date: 2018-05-31