Project acronym CRYSTENG-MOF-MMM
Project Crystal Engineering of Metal Organic Frameworks for application in Mixed Matrix Membranes
Researcher (PI) Jorge Gascon Sabate
Host Institution (HI) TECHNISCHE UNIVERSITEIT DELFT
Call Details Starting Grant (StG), PE8, ERC-2013-StG
Summary With this proposal, I seek to develop the gas separating membranes of the future. The overall aim is to produce composite membranes comprising engineered Metal Organic Framework (MOF) particles and polymers in the form of Mixed Matrix Membranes (MMMs). By applying these new membranes, energetically more efficient separations will be possible.
Despite the superior performance of membranes only based on crystalline materials like zeolites or MOFs, polymeric membranes rule the commercial scene thanks to their easy processing, high reproducibility and mechanical strength. However, the existing polymeric membrane materials are not optimal: improvements in permeability are always at the expense of selectivity and vice versa, while plasticization threatens their application at high pressures. This research aims at utilizing the best of both fields by combining the high selectivity of MOFs with the easy processing of polymers in the form of Mixed Matrix Membranes.
The main barrier to achieve this goal is the optimization of the MOF-polymer interaction and mass transport through the composite. This is very challenging because chemical compatibility, particle morphology and filler dispersion play a key role. Innovatively the project will be the first systematic study into this multi-scale phenomenon with investigations at all relevant interactions, including MOF particle tuning targeting the application in MMMs.
A thorough study on the synthesis of the selected MOF structures and on the performance of the composites will allow engineering MOFs at the molecular and particle levels, resulting in higher selectivity and faster transport. The use of flexible MOF structures will not only allow a better membrane processing but will also reduce polymer plasticization.
This research will deliver a new generation of mixed matrix membranes, outperforming the state of the art polymeric membranes.
Summary
With this proposal, I seek to develop the gas separating membranes of the future. The overall aim is to produce composite membranes comprising engineered Metal Organic Framework (MOF) particles and polymers in the form of Mixed Matrix Membranes (MMMs). By applying these new membranes, energetically more efficient separations will be possible.
Despite the superior performance of membranes only based on crystalline materials like zeolites or MOFs, polymeric membranes rule the commercial scene thanks to their easy processing, high reproducibility and mechanical strength. However, the existing polymeric membrane materials are not optimal: improvements in permeability are always at the expense of selectivity and vice versa, while plasticization threatens their application at high pressures. This research aims at utilizing the best of both fields by combining the high selectivity of MOFs with the easy processing of polymers in the form of Mixed Matrix Membranes.
The main barrier to achieve this goal is the optimization of the MOF-polymer interaction and mass transport through the composite. This is very challenging because chemical compatibility, particle morphology and filler dispersion play a key role. Innovatively the project will be the first systematic study into this multi-scale phenomenon with investigations at all relevant interactions, including MOF particle tuning targeting the application in MMMs.
A thorough study on the synthesis of the selected MOF structures and on the performance of the composites will allow engineering MOFs at the molecular and particle levels, resulting in higher selectivity and faster transport. The use of flexible MOF structures will not only allow a better membrane processing but will also reduce polymer plasticization.
This research will deliver a new generation of mixed matrix membranes, outperforming the state of the art polymeric membranes.
Max ERC Funding
1 467 510 €
Duration
Start date: 2013-09-01, End date: 2018-08-31
Project acronym CRYSYS
Project Crystallisation Systems Engineering – Towards a next generation of intelligent crystallisation systems
Researcher (PI) Zoltan Kalman Nagy
Host Institution (HI) LOUGHBOROUGH UNIVERSITY
Call Details Starting Grant (StG), PE8, ERC-2011-StG_20101014
Summary The project proposes the development of an intelligent crystallisation system by combining state-of-the-art process analytical technologies and novel model-based and statistical feedback control approaches, to provide a fully integrated and adaptive system for efficient engineering of particulate products. The developed adaptive and robust control approaches will be incorporated in a Crystallisation Process Informatics System, to provide an intelligent decision support system, which triggers the suitable control algorithm taking into account the effect of crystallisation on the downstream processing units and final product properties. In this way crystallisation becomes a key intelligent “process actuator” in the whole production system, that manipulates final properties of the solid product taking into account operational, regulatory and economic constraints of the entire process, opening the way towards novel product engineering approaches. The project will bring the implementation of a new generation of integrated, intensified and intelligent crystallisation systems with drastically improved flexibility, predictability, stability and controllability. The system will be used for detailed evaluation of the current paradigm shift from batch to continuous processes in the pharmaceutical industries. Besides providing a breakthrough in crystallisation science the results could revolutionise the methods in which crystallisation will be designed and controlled in the future, yielding to the development of the emerging research field of Pharmaceutical Systems Engineering, by providing a comprehensive framework for the development of novel integrated pharmaceutical production units and product engineering technologies, for sustainable pharmaceutical production, with the aim of reducing time-to-market and increasing product quality, therefore providing considerable increase in quality of life, for example, by making new products available more quickly and at lower cost.
Summary
The project proposes the development of an intelligent crystallisation system by combining state-of-the-art process analytical technologies and novel model-based and statistical feedback control approaches, to provide a fully integrated and adaptive system for efficient engineering of particulate products. The developed adaptive and robust control approaches will be incorporated in a Crystallisation Process Informatics System, to provide an intelligent decision support system, which triggers the suitable control algorithm taking into account the effect of crystallisation on the downstream processing units and final product properties. In this way crystallisation becomes a key intelligent “process actuator” in the whole production system, that manipulates final properties of the solid product taking into account operational, regulatory and economic constraints of the entire process, opening the way towards novel product engineering approaches. The project will bring the implementation of a new generation of integrated, intensified and intelligent crystallisation systems with drastically improved flexibility, predictability, stability and controllability. The system will be used for detailed evaluation of the current paradigm shift from batch to continuous processes in the pharmaceutical industries. Besides providing a breakthrough in crystallisation science the results could revolutionise the methods in which crystallisation will be designed and controlled in the future, yielding to the development of the emerging research field of Pharmaceutical Systems Engineering, by providing a comprehensive framework for the development of novel integrated pharmaceutical production units and product engineering technologies, for sustainable pharmaceutical production, with the aim of reducing time-to-market and increasing product quality, therefore providing considerable increase in quality of life, for example, by making new products available more quickly and at lower cost.
Max ERC Funding
1 263 702 €
Duration
Start date: 2011-09-01, End date: 2017-08-31
Project acronym CUTTINGBUBBLES
Project Bubbles on the Cutting Edge
Researcher (PI) Niels Gerbrand Deen
Host Institution (HI) TECHNISCHE UNIVERSITEIT EINDHOVEN
Call Details Starting Grant (StG), PE8, ERC-2010-StG_20091028
Summary Many processes in the chemical, petrochemical and/or biological industries involve three phase gas-liquidsolid flows, where the solid material acts as a catalyst carrier, the gas phase supplies the reactants for the (bio-)chemical transformations and the liquid phase carries the product. In these processes the performance and operation of the reactor is mostly constrained by the interfacial mass transfer rate and the achievable insitu heat removal rate. A micro-structured bubble column reactor that significantly improves these crucial properties is proposed in this project. This novel type of reactor takes advantage of micro-structuring of the catalyst carrier in the form of a wire-mesh (see Figure 1).
The aim of the wire-mesh is i) to cut bubbles into smaller pieces leading to a larger interfacial area, ii) to enhance the bubble interface dynamics and mass transfer due to the interaction between the bubbles and the wires, and iii) to save costs in practical operation due to the smaller required reactor volume and the fact that
there is no need for an external filtration unit.
Cutting edge three-phase direct numerical simulation (DNS) tools and novel non-invasive optical (highspeed camera) techniques are used to study the micro-scale interaction between bubbles and a wire-mesh to gain understanding of the splitting and merging of bubbles and associated mass transfer characteristics. Furthermore, a proof-of-principle of the micro-structured reactor will be given through lab-scale experiments and macroscopic Euler-Lagrange numerical simulations, employing bubble-wire interaction closures based on the DNS simulations.
In addition to the novel reactor type, the project will generate a broad set of fundamental numerical and experimental research tools that can be used for the improvement of various gas-liquid-solid processes.
Several large companies (AkzoNobel, DSM, Sabic and Shell) have indicated their interest in the proposed
project and would like to be involved in a users committee.
Summary
Many processes in the chemical, petrochemical and/or biological industries involve three phase gas-liquidsolid flows, where the solid material acts as a catalyst carrier, the gas phase supplies the reactants for the (bio-)chemical transformations and the liquid phase carries the product. In these processes the performance and operation of the reactor is mostly constrained by the interfacial mass transfer rate and the achievable insitu heat removal rate. A micro-structured bubble column reactor that significantly improves these crucial properties is proposed in this project. This novel type of reactor takes advantage of micro-structuring of the catalyst carrier in the form of a wire-mesh (see Figure 1).
The aim of the wire-mesh is i) to cut bubbles into smaller pieces leading to a larger interfacial area, ii) to enhance the bubble interface dynamics and mass transfer due to the interaction between the bubbles and the wires, and iii) to save costs in practical operation due to the smaller required reactor volume and the fact that
there is no need for an external filtration unit.
Cutting edge three-phase direct numerical simulation (DNS) tools and novel non-invasive optical (highspeed camera) techniques are used to study the micro-scale interaction between bubbles and a wire-mesh to gain understanding of the splitting and merging of bubbles and associated mass transfer characteristics. Furthermore, a proof-of-principle of the micro-structured reactor will be given through lab-scale experiments and macroscopic Euler-Lagrange numerical simulations, employing bubble-wire interaction closures based on the DNS simulations.
In addition to the novel reactor type, the project will generate a broad set of fundamental numerical and experimental research tools that can be used for the improvement of various gas-liquid-solid processes.
Several large companies (AkzoNobel, DSM, Sabic and Shell) have indicated their interest in the proposed
project and would like to be involved in a users committee.
Max ERC Funding
1 500 000 €
Duration
Start date: 2010-09-01, End date: 2015-08-31
Project acronym D-FENS
Project Dicer-Dependent Defense in Mammals
Researcher (PI) Petr Svoboda
Host Institution (HI) USTAV MOLEKULARNI GENETIKY AKADEMIE VED CESKE REPUBLIKY VEREJNA VYZKUMNA INSTITUCE
Call Details Consolidator Grant (CoG), LS2, ERC-2014-CoG
Summary Viral infection or retrotransposon expansion in the genome often result in production of double-stranded RNA (dsRNA). dsRNA can be intercepted by RNase III Dicer acting in the RNA interference (RNAi) pathway, an ancient eukaryotic defense mechanism. Notably, endogenous mammalian RNAi appears dormant while its common and unique physiological roles remain poorly understood. A factor underlying mammalian RNAi dormancy is inefficient processing of dsRNA by the full-length Dicer. Yet, a simple truncation of Dicer leads to hyperactive RNAi, which is naturally present in mouse oocytes.
The D-FENS project will use genetic animal models to define common, cell-specific and species-specific roles of mammalian RNAi. D-FENS has three complementary and synergizing objectives:
(1) Explore consequences of hyperactive RNAi in vivo. A mouse expressing a truncated Dicer will reveal at the organismal level any negative effect of hyperactive RNAi, the relationship between RNAi and mammalian immune system, and potential of RNAi to suppress viral infections in mammals.
(2) Define common and species-specific features of RNAi in the oocyte. Functional and bioinformatics analyses in mouse, bovine, and hamster oocytes will define rules and exceptions concerning endogenous RNAi roles, including RNAi contribution to maternal mRNA degradation and co-existence with the miRNA pathway.
(3) Uncover relationship between RNAi and piRNA pathways in suppression of retrotransposons. We hypothesize that hyperactive RNAi in mouse oocytes functionally complements the piRNA pathway, a Dicer-independent pathway suppressing retrotransposons in the germline. Using genetic models, we will explore unique and redundant roles of both pathways in the germline.
D-FENS will uncover physiological significance of the N-terminal part of Dicer, fundamentally improve understanding RNAi function in the germline, and provide a critical in vivo assessment of antiviral activity of RNAi with implications for human therapy.
Summary
Viral infection or retrotransposon expansion in the genome often result in production of double-stranded RNA (dsRNA). dsRNA can be intercepted by RNase III Dicer acting in the RNA interference (RNAi) pathway, an ancient eukaryotic defense mechanism. Notably, endogenous mammalian RNAi appears dormant while its common and unique physiological roles remain poorly understood. A factor underlying mammalian RNAi dormancy is inefficient processing of dsRNA by the full-length Dicer. Yet, a simple truncation of Dicer leads to hyperactive RNAi, which is naturally present in mouse oocytes.
The D-FENS project will use genetic animal models to define common, cell-specific and species-specific roles of mammalian RNAi. D-FENS has three complementary and synergizing objectives:
(1) Explore consequences of hyperactive RNAi in vivo. A mouse expressing a truncated Dicer will reveal at the organismal level any negative effect of hyperactive RNAi, the relationship between RNAi and mammalian immune system, and potential of RNAi to suppress viral infections in mammals.
(2) Define common and species-specific features of RNAi in the oocyte. Functional and bioinformatics analyses in mouse, bovine, and hamster oocytes will define rules and exceptions concerning endogenous RNAi roles, including RNAi contribution to maternal mRNA degradation and co-existence with the miRNA pathway.
(3) Uncover relationship between RNAi and piRNA pathways in suppression of retrotransposons. We hypothesize that hyperactive RNAi in mouse oocytes functionally complements the piRNA pathway, a Dicer-independent pathway suppressing retrotransposons in the germline. Using genetic models, we will explore unique and redundant roles of both pathways in the germline.
D-FENS will uncover physiological significance of the N-terminal part of Dicer, fundamentally improve understanding RNAi function in the germline, and provide a critical in vivo assessment of antiviral activity of RNAi with implications for human therapy.
Max ERC Funding
1 950 000 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
Project acronym DALDECS
Project Development and Application of Laser Diagnostic Techniques for Combustion Studies
Researcher (PI) Lars Eric Marcus Aldén
Host Institution (HI) LUNDS UNIVERSITET
Call Details Advanced Grant (AdG), PE8, ERC-2009-AdG
Summary This project is directed towards development of new laser diagnostic techniques and a deepened physical understanding of more established techniques, aiming at new insights in phenomena related to combustion processes. These non-intrusive techniques with high resolution in space and time, will be used for measurements of key parameters, species concentrations and temperatures. The techniques to be used are; Non-linear optical techniques, mainly Polarization spectroscopy, PS. PS will mainly be developed for sensitive detection with high spatial resolution of "new" species in the IR region, e.g. individual hydrocarbons, toxic species as well as alkali metal compounds. Multiplex measurements of these species and temperature will be developed as well as 2D visualization. Quantitative measurements with high precision and accuracy; Laser induced fluorescence and Rayleigh/Raman scattering will be developed for quantitative measurements of species concentration and 2D temperatures. Also a new technique will be developed for single ended experiments based on picosecond LIDAR. Advanced imaging techniques; New high speed (10-100 kHz) visualization techniques as well as 3D and even 4D visualization will be developed. In order to properly visualize dense sprays we will develop Ballistic Imaging as well as a new technique based on structured illumination of the area of interest for suppression of multiple scattering which normally cause blurring effects. All techniques developed above will be used for key studies of phenomena related to various combustion phenomena; turbulent combustion, multiphase conversion processes, e.g. spray combustion and gasification/pyrolysis of solid bio fuels. The techniques will also be applied for development and physical understanding of how combustion could be influenced by plasma/electrical assistance. Finally, the techniques will be prepared for applications in industrial combustion apparatus, e.g. furnaces, gasturbines and IC engines
Summary
This project is directed towards development of new laser diagnostic techniques and a deepened physical understanding of more established techniques, aiming at new insights in phenomena related to combustion processes. These non-intrusive techniques with high resolution in space and time, will be used for measurements of key parameters, species concentrations and temperatures. The techniques to be used are; Non-linear optical techniques, mainly Polarization spectroscopy, PS. PS will mainly be developed for sensitive detection with high spatial resolution of "new" species in the IR region, e.g. individual hydrocarbons, toxic species as well as alkali metal compounds. Multiplex measurements of these species and temperature will be developed as well as 2D visualization. Quantitative measurements with high precision and accuracy; Laser induced fluorescence and Rayleigh/Raman scattering will be developed for quantitative measurements of species concentration and 2D temperatures. Also a new technique will be developed for single ended experiments based on picosecond LIDAR. Advanced imaging techniques; New high speed (10-100 kHz) visualization techniques as well as 3D and even 4D visualization will be developed. In order to properly visualize dense sprays we will develop Ballistic Imaging as well as a new technique based on structured illumination of the area of interest for suppression of multiple scattering which normally cause blurring effects. All techniques developed above will be used for key studies of phenomena related to various combustion phenomena; turbulent combustion, multiphase conversion processes, e.g. spray combustion and gasification/pyrolysis of solid bio fuels. The techniques will also be applied for development and physical understanding of how combustion could be influenced by plasma/electrical assistance. Finally, the techniques will be prepared for applications in industrial combustion apparatus, e.g. furnaces, gasturbines and IC engines
Max ERC Funding
2 466 000 €
Duration
Start date: 2010-02-01, End date: 2015-01-31
Project acronym DAMOC
Project Diabetes Approach by Multi-Organ-on-a-Chip
Researcher (PI) Javier RAMON
Host Institution (HI) FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA
Call Details Starting Grant (StG), PE8, ERC-2016-STG
Summary Insulin secretion and insulin action are critical for normal glucose homeostasis. Defects in both of these processes lead to type 2 diabetes (T2D). Unravelling the mechanisms that lead to T2D is fundamental in the search of new molecular drugs to prevent and control this disease. Organ-on-a-chip devices offer new approaches for T2D disease modelling and drug discovery by providing biologically relevant models of tissues and organs in vitro integrated with biosensors. As such, organ-on-a-chip devices have the potential to revolutionize the pharmaceutical industry by enabling reliable and high predictive in vitro testing of drug candidates. The capability to miniaturize biosensor systems and advanced tissue fabrication procedures have enabled researchers to create multiple tissues on a chip with a high degree of control over experimental variables for high-content screening applications. The goal of this project is the fabrication of a biomimetic multi organ-on-a-chip integrated device composed of skeletal muscle and pancreatic islets for studying metabolism glucose diseases and for drug screening applications. Engineered muscle tissues and pancreatic islets are integrated with the technology to detect the glucose consumption, contraction induced glucose metabolism, insulin secretion and protein biomarker secretion of cells. We aim to design a novel therapeutic tool to test drugs with a multi organ-on-a-chip device. Such finding would improve drug test approaches and would provide for new therapies to prevent the loss of beta cell mass associated with T2D and defects in the glucose uptake in skeletal muscle.
Summary
Insulin secretion and insulin action are critical for normal glucose homeostasis. Defects in both of these processes lead to type 2 diabetes (T2D). Unravelling the mechanisms that lead to T2D is fundamental in the search of new molecular drugs to prevent and control this disease. Organ-on-a-chip devices offer new approaches for T2D disease modelling and drug discovery by providing biologically relevant models of tissues and organs in vitro integrated with biosensors. As such, organ-on-a-chip devices have the potential to revolutionize the pharmaceutical industry by enabling reliable and high predictive in vitro testing of drug candidates. The capability to miniaturize biosensor systems and advanced tissue fabrication procedures have enabled researchers to create multiple tissues on a chip with a high degree of control over experimental variables for high-content screening applications. The goal of this project is the fabrication of a biomimetic multi organ-on-a-chip integrated device composed of skeletal muscle and pancreatic islets for studying metabolism glucose diseases and for drug screening applications. Engineered muscle tissues and pancreatic islets are integrated with the technology to detect the glucose consumption, contraction induced glucose metabolism, insulin secretion and protein biomarker secretion of cells. We aim to design a novel therapeutic tool to test drugs with a multi organ-on-a-chip device. Such finding would improve drug test approaches and would provide for new therapies to prevent the loss of beta cell mass associated with T2D and defects in the glucose uptake in skeletal muscle.
Max ERC Funding
1 499 554 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym DAMONA
Project Mutation and Recombination in the Cattle Germline: Genomic Analysis and Impact on Fertility
Researcher (PI) Michel Alphonse Julien Georges
Host Institution (HI) UNIVERSITE DE LIEGE
Call Details Advanced Grant (AdG), LS2, ERC-2012-ADG_20120314
Summary "Mutation and recombination are fundamental biological processes that determine adaptability of populations. The mutation rate reflects the equilibrium between the need to adapt, the burden of mutation load, the “cost of fidelity”, and random drift that determines a lower limit in achievable fidelity. Recombination fulfills an essential mechanistic role during meiosis, ensuring proper chromosomal segregation. Recombination affects the rate of creation and loss of favorable haplotypes, imposing 2nd-order selection pressure on modifiers of recombination.
It is becoming apparent that recombination and mutation rates vary between individuals, and that these differences are in part inherited. Both processes are therefore “evolvable”, and amenable to genomic analysis. Identifying genetic determinants underlying these differences will provide insights in the regulation of mutation and recombination. The mutational load, and in particular the number of lethal equivalents per individual, remains poorly defined as epidemiological and molecular data yield estimates that differ by one order of magnitude. A relationship between recombination and fertility has been reported in women but awaits confirmation.
Population structure (small effective population size; large harems), phenotypic data collection (systematic recording of > 50 traits on millions of cows), and large-scale SNP genotyping (for genomic selection), make cattle populations uniquely suited for genetic analysis. DAMONA proposes to exploit these unique resources, combined with recent advances in next generation sequencing and genotyping, to:
(i) quantify and characterize inter-individual variation in male and female mutation and recombination rates,
(ii) map, fine-map and identify causative genes underlying QTL for these four phenotypes,
(iii) test the effect of loss-of-function variants on >50 traits including fertility, and
(iv) study the effect of variation in recombination on fertility."
Summary
"Mutation and recombination are fundamental biological processes that determine adaptability of populations. The mutation rate reflects the equilibrium between the need to adapt, the burden of mutation load, the “cost of fidelity”, and random drift that determines a lower limit in achievable fidelity. Recombination fulfills an essential mechanistic role during meiosis, ensuring proper chromosomal segregation. Recombination affects the rate of creation and loss of favorable haplotypes, imposing 2nd-order selection pressure on modifiers of recombination.
It is becoming apparent that recombination and mutation rates vary between individuals, and that these differences are in part inherited. Both processes are therefore “evolvable”, and amenable to genomic analysis. Identifying genetic determinants underlying these differences will provide insights in the regulation of mutation and recombination. The mutational load, and in particular the number of lethal equivalents per individual, remains poorly defined as epidemiological and molecular data yield estimates that differ by one order of magnitude. A relationship between recombination and fertility has been reported in women but awaits confirmation.
Population structure (small effective population size; large harems), phenotypic data collection (systematic recording of > 50 traits on millions of cows), and large-scale SNP genotyping (for genomic selection), make cattle populations uniquely suited for genetic analysis. DAMONA proposes to exploit these unique resources, combined with recent advances in next generation sequencing and genotyping, to:
(i) quantify and characterize inter-individual variation in male and female mutation and recombination rates,
(ii) map, fine-map and identify causative genes underlying QTL for these four phenotypes,
(iii) test the effect of loss-of-function variants on >50 traits including fertility, and
(iv) study the effect of variation in recombination on fertility."
Max ERC Funding
2 258 000 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym DAMREG
Project Pushing the Frontier of Brittlness
Damage Resistant Glasses
Researcher (PI) Tanguy Gilles Michel Rouxel
Host Institution (HI) UNIVERSITE DE RENNES I
Call Details Advanced Grant (AdG), PE8, ERC-2012-ADG_20120216
Summary "In order to improve the strength of a glass part (flat display, window, lens, fiber, etc.), most investigations so far were devoted to thermal and chemical surface treatments aimed at generating compressive stresses at the surface. The DAMREG project focuses on the incidence of the glass composition and atomic network structure on the mechanical properties, and specifically on the cracking and fracture behavior, and is based on the experience and expertise of the PI on the structure-property relationships in glass science. This project proposes to address the fundamental issue of glass brittleness in a new paradigm of thinking, questioning the usefulness of the standard fracture toughness parameter, with emphasis on the surface flaw generation process (multiscale approach), and aims at determining novel routes to improve the mechanical performance of glass further promoting innovative applications. DAMREG involves revisiting the fundamental fracture mechanics concepts, the preparation of novel glass compositions, and nanoscale physico-chemical and mechanical characterization. So far most glass fracture studies focused on the crack tip behavior, and were limited to vitreous silica. A crack acts as a lever arm for the stress so that the singular stress at the tip is proportional to the crack length and inversely proportional to the square-root of the tip radius (provided this has a meaning). Since a crack can hardly be cured or shielded at ambient, the presence of a sharp crack is already detrimental. On the contrary to this approach, DAMREG is aimed at understanding the crack initiation process, and the main objective is to define some roadmap to design glasses (composition, thermo-mechanical treatments etc.) with better damage (initiation) resistance."
Summary
"In order to improve the strength of a glass part (flat display, window, lens, fiber, etc.), most investigations so far were devoted to thermal and chemical surface treatments aimed at generating compressive stresses at the surface. The DAMREG project focuses on the incidence of the glass composition and atomic network structure on the mechanical properties, and specifically on the cracking and fracture behavior, and is based on the experience and expertise of the PI on the structure-property relationships in glass science. This project proposes to address the fundamental issue of glass brittleness in a new paradigm of thinking, questioning the usefulness of the standard fracture toughness parameter, with emphasis on the surface flaw generation process (multiscale approach), and aims at determining novel routes to improve the mechanical performance of glass further promoting innovative applications. DAMREG involves revisiting the fundamental fracture mechanics concepts, the preparation of novel glass compositions, and nanoscale physico-chemical and mechanical characterization. So far most glass fracture studies focused on the crack tip behavior, and were limited to vitreous silica. A crack acts as a lever arm for the stress so that the singular stress at the tip is proportional to the crack length and inversely proportional to the square-root of the tip radius (provided this has a meaning). Since a crack can hardly be cured or shielded at ambient, the presence of a sharp crack is already detrimental. On the contrary to this approach, DAMREG is aimed at understanding the crack initiation process, and the main objective is to define some roadmap to design glasses (composition, thermo-mechanical treatments etc.) with better damage (initiation) resistance."
Max ERC Funding
1 821 596 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym DARCGENS
Project Derived and Ancestral RNAs: Comparative Genomics and Evolution of ncRNAs
Researcher (PI) Christopher Paul Ponting
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), LS2, ERC-2009-AdG
Summary Much light has been shed on the number, mechanisms and functions of protein-coding genes in the human genome. In comparison, we know almost nothing about the origins and mechanisms of the functional dark matter , including sequence that is transcribed outside of protein-coding gene loci. This interdisciplinary proposal will capitalize on new theoretical and experimental opportunities to establish the extent by which long non-coding RNAs contribute to mammalian and fruit fly biology. Since 2001, the Ponting group has pioneered the comparative analysis of protein-coding genes across the amniotes and Drosophilids within many international genome sequencing consortia. This Advanced Grant will break new ground by applying these approaches to long intergenic non-coding RNA (lincRNA) genes from mammals to birds and to flies. The Grant will allow Ponting to free himself of the constraints normally associated with in silico analyses by analysing lincRNAs in vitro and in vivo. The integration of computational and experimental approaches for lincRNAs from across the metazoan tree provides a powerful new toolkit for elucidating the origins and biological roles of these enigmatic molecules. Catalogues of lincRNA loci will be built for human, mouse, fruit fly, zebrafinch, chicken and Aplysia by exploiting data from next-generation sequencing technologies. This will immediately provide a new perspective on how these loci arise, evolve and function, including whether their orthologues are apparent across diverse species. Using new evidence that lincRNA loci act in cis with neighbouring protein-coding loci, we will determine lincRNA mechanisms and will establish the consequences of lincRNA knock-down, knock-out and over-expression in mouse, chick and fruitfly.
Summary
Much light has been shed on the number, mechanisms and functions of protein-coding genes in the human genome. In comparison, we know almost nothing about the origins and mechanisms of the functional dark matter , including sequence that is transcribed outside of protein-coding gene loci. This interdisciplinary proposal will capitalize on new theoretical and experimental opportunities to establish the extent by which long non-coding RNAs contribute to mammalian and fruit fly biology. Since 2001, the Ponting group has pioneered the comparative analysis of protein-coding genes across the amniotes and Drosophilids within many international genome sequencing consortia. This Advanced Grant will break new ground by applying these approaches to long intergenic non-coding RNA (lincRNA) genes from mammals to birds and to flies. The Grant will allow Ponting to free himself of the constraints normally associated with in silico analyses by analysing lincRNAs in vitro and in vivo. The integration of computational and experimental approaches for lincRNAs from across the metazoan tree provides a powerful new toolkit for elucidating the origins and biological roles of these enigmatic molecules. Catalogues of lincRNA loci will be built for human, mouse, fruit fly, zebrafinch, chicken and Aplysia by exploiting data from next-generation sequencing technologies. This will immediately provide a new perspective on how these loci arise, evolve and function, including whether their orthologues are apparent across diverse species. Using new evidence that lincRNA loci act in cis with neighbouring protein-coding loci, we will determine lincRNA mechanisms and will establish the consequences of lincRNA knock-down, knock-out and over-expression in mouse, chick and fruitfly.
Max ERC Funding
2 400 000 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym DARE
Project Soil Foundation Structure Systems Beyond Conventional Seismic Failure Thresholds: Application to New or Existing Structures and Monuments
Researcher (PI) George Gazetas
Host Institution (HI) NATIONAL TECHNICAL UNIVERSITY OF ATHENS - NTUA
Call Details Advanced Grant (AdG), PE8, ERC-2008-AdG
Summary The main goal of the proposed research is to investigate the possibility of allowing below-ground support systems to respond to strong seismic shaking by going beyond a number of thresholds that would conventionally imply failure and are today forbidden by codes. Such thresholds include : (a) sliding at the soil-foundation interface ; (b) separation and uplifting of a shallow foundation from the soils ; (c) mobilization of bearing capacity failure mechanism for shallow foundations ; (d) structural yielding of pile foundations ; (e) combination of some of the above. Whereas under static loading conditions a slight exceedance of such thresholds leads to failure, the oscillatory nature of seismic shaking will allow such exceedances for a short period of time, with perhaps no detrimental or irreparable consequences. The latter take the form of permanent foundation displacements, rotations, or injuries , which the designer will aspire to confine within rational limits. The motivation and the need for this research has come from : (i) observations of actual behaviour in a variety of earthquakes ; conspicuous examples : the permanent tilting , overturning, and often survival of numerous buildings on extremely soft soil in Adapazari during the Kocaeli 1999 earthquake ; (ii) the foundation design of a number of critical structures (e.g., major bridge pier, air control tower, tall monuments, elevated water tanks,) against large seismic actions ; the disproportionately large overturning moment and/or base shear force of such slender structures can hardly be faced with today s conventional foundation methods, (iii) the need to seismically retrofit and rehabilitate older structures and historical monuments; (iv) structural yielding of pile foundations is now detectable (thanks to technological advances), thus eliminating one of the reasons for avoiding it.
Summary
The main goal of the proposed research is to investigate the possibility of allowing below-ground support systems to respond to strong seismic shaking by going beyond a number of thresholds that would conventionally imply failure and are today forbidden by codes. Such thresholds include : (a) sliding at the soil-foundation interface ; (b) separation and uplifting of a shallow foundation from the soils ; (c) mobilization of bearing capacity failure mechanism for shallow foundations ; (d) structural yielding of pile foundations ; (e) combination of some of the above. Whereas under static loading conditions a slight exceedance of such thresholds leads to failure, the oscillatory nature of seismic shaking will allow such exceedances for a short period of time, with perhaps no detrimental or irreparable consequences. The latter take the form of permanent foundation displacements, rotations, or injuries , which the designer will aspire to confine within rational limits. The motivation and the need for this research has come from : (i) observations of actual behaviour in a variety of earthquakes ; conspicuous examples : the permanent tilting , overturning, and often survival of numerous buildings on extremely soft soil in Adapazari during the Kocaeli 1999 earthquake ; (ii) the foundation design of a number of critical structures (e.g., major bridge pier, air control tower, tall monuments, elevated water tanks,) against large seismic actions ; the disproportionately large overturning moment and/or base shear force of such slender structures can hardly be faced with today s conventional foundation methods, (iii) the need to seismically retrofit and rehabilitate older structures and historical monuments; (iv) structural yielding of pile foundations is now detectable (thanks to technological advances), thus eliminating one of the reasons for avoiding it.
Max ERC Funding
2 399 992 €
Duration
Start date: 2008-12-01, End date: 2013-10-31
Project acronym DARK
Project Dark matter of the human transcriptome: Functional study of the antisense Long Noncoding RNAs and Molecular Mechanisms of Action
Researcher (PI) Antonin Morillon
Host Institution (HI) INSTITUT CURIE
Call Details Consolidator Grant (CoG), LS2, ERC-2013-CoG
Summary 98% of the human genome is non-protein coding raising the question of the role of the dark matter of the genome. It is now admitted that pervasive transcription generates thousands of noncoding transcripts that regulate gene expression and have broad impacts on development and disease. Among the long non coding (lnc)RNAs, antisense transcripts have been poorly studied despite their putative regulatory importance. Several functional examples include X-chromosome inactivation, maintenance of pluripotency and transcriptional regulation. However, no systematic study has yet addressed the comprehensive functional description of human antisense ncRNA, mainly because of technological issues and their low abundance. Indeed, in budding yeast S. cerevisiae, our group showed the existence of an entire class of antisense regulatory lncRNA extremely sensitive to RNA decay pathways, impinging their study so far. The roles for yeast antisense lncRNAs in shaping the epigenome raises important questions: What are the molecular and biochemical mechanisms by which antisense lncRNAs carry out their functions and are they functionally conserved in human cells? We propose that the dark side of the non-coding genome is another layer of gene regulation complexity that needs to be deciphered.
With this proposal, we aim to draw the first exhaustive catalog of human antisense lncRNA in various cell types and tissues using up to date High throughput technologies and bioinformatics pipelines. Second, we propose to determine the functional role of antisense lncRNA on genome expression and stability in the context of cellular stress and cancer. We anticipate that powerful and modern genetic tools such DNA-mediated gene inactivation (ASO) and TALEN approaches will allow precise antisense genes manipulation never achieved so far. Our project is strongly supported by preliminary data indicating an unexpected large number of hidden antisense lncRNA in human cells controlled by RNA decay pathways.
Summary
98% of the human genome is non-protein coding raising the question of the role of the dark matter of the genome. It is now admitted that pervasive transcription generates thousands of noncoding transcripts that regulate gene expression and have broad impacts on development and disease. Among the long non coding (lnc)RNAs, antisense transcripts have been poorly studied despite their putative regulatory importance. Several functional examples include X-chromosome inactivation, maintenance of pluripotency and transcriptional regulation. However, no systematic study has yet addressed the comprehensive functional description of human antisense ncRNA, mainly because of technological issues and their low abundance. Indeed, in budding yeast S. cerevisiae, our group showed the existence of an entire class of antisense regulatory lncRNA extremely sensitive to RNA decay pathways, impinging their study so far. The roles for yeast antisense lncRNAs in shaping the epigenome raises important questions: What are the molecular and biochemical mechanisms by which antisense lncRNAs carry out their functions and are they functionally conserved in human cells? We propose that the dark side of the non-coding genome is another layer of gene regulation complexity that needs to be deciphered.
With this proposal, we aim to draw the first exhaustive catalog of human antisense lncRNA in various cell types and tissues using up to date High throughput technologies and bioinformatics pipelines. Second, we propose to determine the functional role of antisense lncRNA on genome expression and stability in the context of cellular stress and cancer. We anticipate that powerful and modern genetic tools such DNA-mediated gene inactivation (ASO) and TALEN approaches will allow precise antisense genes manipulation never achieved so far. Our project is strongly supported by preliminary data indicating an unexpected large number of hidden antisense lncRNA in human cells controlled by RNA decay pathways.
Max ERC Funding
1 998 884 €
Duration
Start date: 2014-12-01, End date: 2019-11-30
Project acronym DCFM
Project Default and Collateral in Financial Markets
Researcher (PI) Ioannis Vailakis
Host Institution (HI) THE UNIVERSITY OF EXETER
Call Details Starting Grant (StG), SH1, ERC-2009-StG
Summary The main objective of this project is to research the economic implications of default and collateral in financial markets. It is motivated from the observation that much of the lending in modern economies is secured by some form of collateral and by the empirical fact that modern economies experience a substantial amount of default and bankruptcy. From a theoretical perspective, the research aims to explore new ways of modelling default and collateral and employ them to evaluate the impact of default and collateral on market outcomes. From a policy recommendation perspective, the research aims to develop models with testable implications that can be used by practitioners to discuss the consequences of a wide range of policies. In particular, to explore which kind of regulation procedures should be implemented in order to lower the risk of default and at the same time not to reduce too much risk-sharing. The agenda includes two research directions. The first research direction will focus on the implications of default and collateral in economies with bounded rational agents. Our aim is to understand how default and collateral affect market outcomes in environments where agents are allowed to have very divergent and therefore possibly incorrect beliefs about endogenous economic variables like future prices and delivery rates. The second research direction will focus on the implications of default and collateral in economies with an open ended horizon. Our aim is to investigate endogenous debt constraints that are compatible with equilibrium and simultaneously allow for as much risk sharing as possible.
Summary
The main objective of this project is to research the economic implications of default and collateral in financial markets. It is motivated from the observation that much of the lending in modern economies is secured by some form of collateral and by the empirical fact that modern economies experience a substantial amount of default and bankruptcy. From a theoretical perspective, the research aims to explore new ways of modelling default and collateral and employ them to evaluate the impact of default and collateral on market outcomes. From a policy recommendation perspective, the research aims to develop models with testable implications that can be used by practitioners to discuss the consequences of a wide range of policies. In particular, to explore which kind of regulation procedures should be implemented in order to lower the risk of default and at the same time not to reduce too much risk-sharing. The agenda includes two research directions. The first research direction will focus on the implications of default and collateral in economies with bounded rational agents. Our aim is to understand how default and collateral affect market outcomes in environments where agents are allowed to have very divergent and therefore possibly incorrect beliefs about endogenous economic variables like future prices and delivery rates. The second research direction will focus on the implications of default and collateral in economies with an open ended horizon. Our aim is to investigate endogenous debt constraints that are compatible with equilibrium and simultaneously allow for as much risk sharing as possible.
Max ERC Funding
156 538 €
Duration
Start date: 2010-06-01, End date: 2012-06-30
Project acronym DDD
Project Diffusive Droplet Dynamics in multicomponent fluid systems
Researcher (PI) Detlef Lohse
Host Institution (HI) UNIVERSITEIT TWENTE
Call Details Advanced Grant (AdG), PE8, ERC-2016-ADG
Summary Liquid-liquid extraction - the transfer of a solute from one solvent to another - is a core process in chemical technology and analysis. The current challenge is to miniaturise the analyte extraction process and to optimize the extraction recovery and preconcentration factor. Lacking a priori calculations, this is now often done by trial-and-error. However, to control and optimize the extraction processes, it is crucial to quantitatively understand the diffusive droplet dynamics in multicomponent fluid systems. This is essential and urgently needed not only for modern liquid-liquid extraction processes for diagnostics & microanalysis, for droplet microfluidics, or in the paint & coating industry, but on larger scales also in remediation industry, in chemical technology, or in food processing. These applications of droplets governed by diffusion include cases of immersed droplets in the bulk & on a surface, single & multicomponent droplets & solvents, and cases with high droplet number density. In spite of their relevance, multiphase & multicomponent fluid systems with relevant diffusive droplet dynamics are poorly understood.
The objective of DDD is a breakthrough: to fill this gap and to come to a quantitative understanding of diffusive droplet dynamics, thus illuminating the fundamental fluid dynamics of diffusive processes of immersed (multicomponent) (surface) droplets on multiple scales. To achieve this objective, we will perform a number of key controlled experiments and numerical simulations for idealized setups on 9 orders of magnitude in length scale, allowing for one-to-one comparison between experiments and numerics/theory. It is now time to bridge the gap from modern fluid dynamics to process-technology, colloidal & interface science, from nano/microscopic and purely diffusively governed droplets to macroscopic ones and from single droplets to multiple & multi-component droplets, to arrive at multiscale high-precision chemical engineering for droplets.
Summary
Liquid-liquid extraction - the transfer of a solute from one solvent to another - is a core process in chemical technology and analysis. The current challenge is to miniaturise the analyte extraction process and to optimize the extraction recovery and preconcentration factor. Lacking a priori calculations, this is now often done by trial-and-error. However, to control and optimize the extraction processes, it is crucial to quantitatively understand the diffusive droplet dynamics in multicomponent fluid systems. This is essential and urgently needed not only for modern liquid-liquid extraction processes for diagnostics & microanalysis, for droplet microfluidics, or in the paint & coating industry, but on larger scales also in remediation industry, in chemical technology, or in food processing. These applications of droplets governed by diffusion include cases of immersed droplets in the bulk & on a surface, single & multicomponent droplets & solvents, and cases with high droplet number density. In spite of their relevance, multiphase & multicomponent fluid systems with relevant diffusive droplet dynamics are poorly understood.
The objective of DDD is a breakthrough: to fill this gap and to come to a quantitative understanding of diffusive droplet dynamics, thus illuminating the fundamental fluid dynamics of diffusive processes of immersed (multicomponent) (surface) droplets on multiple scales. To achieve this objective, we will perform a number of key controlled experiments and numerical simulations for idealized setups on 9 orders of magnitude in length scale, allowing for one-to-one comparison between experiments and numerics/theory. It is now time to bridge the gap from modern fluid dynamics to process-technology, colloidal & interface science, from nano/microscopic and purely diffusively governed droplets to macroscopic ones and from single droplets to multiple & multi-component droplets, to arrive at multiscale high-precision chemical engineering for droplets.
Max ERC Funding
2 937 500 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym DECODE
Project Decoding the complexity of quantitative natural variation in Arabidopsis thaliana
Researcher (PI) Olivier Loudet
Host Institution (HI) INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE
Call Details Starting Grant (StG), LS2, ERC-2009-StG
Summary Following a long history of quantitative genetics in crop plants, it now becomes feasible to use naturally-occuring variation contained in Arabidopsis thaliana accessions (lines isolated from natural populations) as the source of quantitative genomics approaches, designed to map QTLs and resolve them at the gene level. Apart from being able to exploit in multiple genetic backgrounds allelic variation that cannot be easily generated by conventional mutagenesis, the (relatively few) success of the QTL studies has often been because of the use of quantitative phenotyping, as opposed to the qualitative gauges used in typical mutant screens. Among the various genetic mechanisms responsible for natural variation that have just started to be revealed, cis-acting regulation is potentially of large impact, despite remaining more difficult to recognize and confirm. The objective of this project is to apply genome-wide quantitative molecular genetics to both, a very integrative and classical quantitative trait (growth in interaction with the environment) and a molecular trait a priori more directly linked to the source of variation (gene expression under cis-regulation). We propose to use a combination of our unique high-troughput phenotyping robot, fine-mapping, complementation approaches and association genetics to pinpoint a significant number of QTLs and eQTLs to the gene level and identify causative polymorphisms and the molecular variation controlling natural diversity. Working at an unprecedented scale should finally allow to resolve enough quantitative loci and pay a significant contribution to drawing a general picture as to how and where in the pathways adaptation is shaping natural variation and improve our understanding of the transcriptional cis-regulatory code.
Summary
Following a long history of quantitative genetics in crop plants, it now becomes feasible to use naturally-occuring variation contained in Arabidopsis thaliana accessions (lines isolated from natural populations) as the source of quantitative genomics approaches, designed to map QTLs and resolve them at the gene level. Apart from being able to exploit in multiple genetic backgrounds allelic variation that cannot be easily generated by conventional mutagenesis, the (relatively few) success of the QTL studies has often been because of the use of quantitative phenotyping, as opposed to the qualitative gauges used in typical mutant screens. Among the various genetic mechanisms responsible for natural variation that have just started to be revealed, cis-acting regulation is potentially of large impact, despite remaining more difficult to recognize and confirm. The objective of this project is to apply genome-wide quantitative molecular genetics to both, a very integrative and classical quantitative trait (growth in interaction with the environment) and a molecular trait a priori more directly linked to the source of variation (gene expression under cis-regulation). We propose to use a combination of our unique high-troughput phenotyping robot, fine-mapping, complementation approaches and association genetics to pinpoint a significant number of QTLs and eQTLs to the gene level and identify causative polymorphisms and the molecular variation controlling natural diversity. Working at an unprecedented scale should finally allow to resolve enough quantitative loci and pay a significant contribution to drawing a general picture as to how and where in the pathways adaptation is shaping natural variation and improve our understanding of the transcriptional cis-regulatory code.
Max ERC Funding
1 742 113 €
Duration
Start date: 2010-02-01, End date: 2016-01-31
Project acronym DECORE
Project Deep Earth Chemistry of the Core
Researcher (PI) James Badro
Host Institution (HI) INSTITUT DE PHYSIQUE DU GLOBE DE PARIS
Call Details Starting Grant (StG), PE8, ERC-2007-StG
Summary Core formation represents the major chemical differentiation event on the terrestrial planets, involving the separation of a metallic liquid from the silicate matrix that subsequently evolves into the current silicate crust and mantle. The generation of the Earth’s magnetic field is ultimately tied to the segregation and crystallization of the core, and is an important factor in establishing planetary habitability. The processes that control core segregation and the depths and temperatures at which this process took place are poorly understood, however. We propose to study those processes. Specifically, the density of the core is lower than would be expected for pure iron, indicating that a light component (O, Si, S, C, H) must be present. Similarly, the Earth’s mantle is richer in iron-loving (“siderophile”) elements, e.g, V, W, Mo, Ru, Pd, etc., than would be expected based upon low pressure metal-silicate partitioning data. Solutions to these problems are hampered by the pressure range of existing experimental data, < 25 GPa, equivalent to ~700 km in the Earth. We propose to extend the accessible range of pressures and temperatures by developing protocols that link the laser-heated diamond anvil cell with analytical techniques such as (i) the NanoSIMS, (ii) the focused ion beam device (FIB), (iii) and transmission and secondary electron microscopy, allowing us to obtain quantitative data on element partitioning and chemical composition at extreme conditions relevant to the Earth’s lower mantle. The technical motivation follows from the fact that the real limitation on trace element partitioning studies at ultra high-pressure has been the grain size of the phases produced at high P-T, relative to the spatial resolution of the analytical methods available to probe the experiments; we can bridge the gap by combining state-of-the-art laser heating experiments with new nano-scale analytical techniques.
Summary
Core formation represents the major chemical differentiation event on the terrestrial planets, involving the separation of a metallic liquid from the silicate matrix that subsequently evolves into the current silicate crust and mantle. The generation of the Earth’s magnetic field is ultimately tied to the segregation and crystallization of the core, and is an important factor in establishing planetary habitability. The processes that control core segregation and the depths and temperatures at which this process took place are poorly understood, however. We propose to study those processes. Specifically, the density of the core is lower than would be expected for pure iron, indicating that a light component (O, Si, S, C, H) must be present. Similarly, the Earth’s mantle is richer in iron-loving (“siderophile”) elements, e.g, V, W, Mo, Ru, Pd, etc., than would be expected based upon low pressure metal-silicate partitioning data. Solutions to these problems are hampered by the pressure range of existing experimental data, < 25 GPa, equivalent to ~700 km in the Earth. We propose to extend the accessible range of pressures and temperatures by developing protocols that link the laser-heated diamond anvil cell with analytical techniques such as (i) the NanoSIMS, (ii) the focused ion beam device (FIB), (iii) and transmission and secondary electron microscopy, allowing us to obtain quantitative data on element partitioning and chemical composition at extreme conditions relevant to the Earth’s lower mantle. The technical motivation follows from the fact that the real limitation on trace element partitioning studies at ultra high-pressure has been the grain size of the phases produced at high P-T, relative to the spatial resolution of the analytical methods available to probe the experiments; we can bridge the gap by combining state-of-the-art laser heating experiments with new nano-scale analytical techniques.
Max ERC Funding
1 509 200 €
Duration
Start date: 2008-11-01, End date: 2013-10-31
Project acronym DEFTPORE
Project Deformation control on flow and transport in soft porous media
Researcher (PI) Christopher MacMinn
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Starting Grant (StG), PE8, ERC-2018-STG
Summary Fluid flows through soft porous media are ubiquitous across nature and industry, from methane bubbles rising through lakebed and seabed sediments to nutrient transport in living cells and tissues to the manufacturing of paper products and many composites. Despite their ubiquity, flow and transport in these systems remain at the frontier of our ability to measure and model. A defining feature of soft porous media is that they can experience deformations that transform the pore structure. This has profound implications for the transport and mixing of solutes and the simultaneous flow of multiple fluid phases, both of which are strongly coupled to the pore structure. The goal of this project is to shed new light on flow and transport in soft porous media by studying a series of three canonical flow problems (tracer transport, miscible viscous fingering, and two-phase flow) across soft adaptations of three classical model systems (a soft-walled Hele Shaw cell, a quasi-2D packing of soft beads, and a cylindrical 3D “core” of soft beads). These flow problems and model systems have been thoroughly studied in the context of stiff porous media, allowing us to leverage decades of previous work and focus exclusively on the new behaviour introduced by “softness”. We will collect an extensive set of new, high-resolution experimental observations in each of these model systems, and we will reconcile these observations with mathematical models based on the traditional approach of upscaled constitutive functions. By updating this traditional approach to account for deformation, we will provide a new, pragmatic class of continuum models that capture the leading-order features of flow and transport in soft porous media. Our results will jumpstart the field of flow and transport in soft porous media, breaking open a vast new realm of research questions and applications around understanding, predicting, and controlling these complex systems.
Summary
Fluid flows through soft porous media are ubiquitous across nature and industry, from methane bubbles rising through lakebed and seabed sediments to nutrient transport in living cells and tissues to the manufacturing of paper products and many composites. Despite their ubiquity, flow and transport in these systems remain at the frontier of our ability to measure and model. A defining feature of soft porous media is that they can experience deformations that transform the pore structure. This has profound implications for the transport and mixing of solutes and the simultaneous flow of multiple fluid phases, both of which are strongly coupled to the pore structure. The goal of this project is to shed new light on flow and transport in soft porous media by studying a series of three canonical flow problems (tracer transport, miscible viscous fingering, and two-phase flow) across soft adaptations of three classical model systems (a soft-walled Hele Shaw cell, a quasi-2D packing of soft beads, and a cylindrical 3D “core” of soft beads). These flow problems and model systems have been thoroughly studied in the context of stiff porous media, allowing us to leverage decades of previous work and focus exclusively on the new behaviour introduced by “softness”. We will collect an extensive set of new, high-resolution experimental observations in each of these model systems, and we will reconcile these observations with mathematical models based on the traditional approach of upscaled constitutive functions. By updating this traditional approach to account for deformation, we will provide a new, pragmatic class of continuum models that capture the leading-order features of flow and transport in soft porous media. Our results will jumpstart the field of flow and transport in soft porous media, breaking open a vast new realm of research questions and applications around understanding, predicting, and controlling these complex systems.
Max ERC Funding
1 482 862 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym DemandDemoc
Project Demand for Democracy
Researcher (PI) Davide Werner CANTONI
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Starting Grant (StG), SH1, ERC-2016-STG
Summary Historically, people around the world have demanded democratic institutions. Such democratic movements propel political change and also determine economic outcomes. In this project, we ask, how do political preferences, beliefs, and second-order beliefs shape the strategic decision to participate in a movement demanding democracy? Existing scholarship is unsatisfactory because it is conducted ex post: preferences, beliefs, and behavior have converged to a new equilibrium. In contrast, we examine a democratic movement in real time, studying the ongoing democracy movement in Hong Kong.
Our study is composed of four parts. In Part 1, we collect panel survey data from Hong Kong university students, a particularly politically active subpopulation. We collect data on preferences, behavior, beliefs, and second-order beliefs using incentivized and indirect elicitation to encourage truthful reporting. We analyze the associations among these variables to shed light on the drivers of participation in the democracy movement.
In Part 2, we exploit experimental variation in the provision of information to study political coordination. Among participants in the panel survey, we provide information regarding the preferences and beliefs of other students. We examine whether exposure to information regarding peers causes students to update their beliefs and change their behavior.
In Part 3, we extend the analysis in Part 1 to a nationally representative sample of Hong Kong citizens. To do so, we have added a module regarding political preferences, beliefs, and behavior (including incentivized questions and questions providing cover for responses to politically sensitive topics) to the HKPSSD panel survey.
In Part 4, we study preferences for redistribution – plausibly a central driver for demands for political rights – among Hong Kong citizens and mainland Chinese. We examine how these preferences differ across populations, as well as their link to support for democracy.
Summary
Historically, people around the world have demanded democratic institutions. Such democratic movements propel political change and also determine economic outcomes. In this project, we ask, how do political preferences, beliefs, and second-order beliefs shape the strategic decision to participate in a movement demanding democracy? Existing scholarship is unsatisfactory because it is conducted ex post: preferences, beliefs, and behavior have converged to a new equilibrium. In contrast, we examine a democratic movement in real time, studying the ongoing democracy movement in Hong Kong.
Our study is composed of four parts. In Part 1, we collect panel survey data from Hong Kong university students, a particularly politically active subpopulation. We collect data on preferences, behavior, beliefs, and second-order beliefs using incentivized and indirect elicitation to encourage truthful reporting. We analyze the associations among these variables to shed light on the drivers of participation in the democracy movement.
In Part 2, we exploit experimental variation in the provision of information to study political coordination. Among participants in the panel survey, we provide information regarding the preferences and beliefs of other students. We examine whether exposure to information regarding peers causes students to update their beliefs and change their behavior.
In Part 3, we extend the analysis in Part 1 to a nationally representative sample of Hong Kong citizens. To do so, we have added a module regarding political preferences, beliefs, and behavior (including incentivized questions and questions providing cover for responses to politically sensitive topics) to the HKPSSD panel survey.
In Part 4, we study preferences for redistribution – plausibly a central driver for demands for political rights – among Hong Kong citizens and mainland Chinese. We examine how these preferences differ across populations, as well as their link to support for democracy.
Max ERC Funding
1 494 647 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym DEMONS
Project Deciphering Eruptions by Modeling Outputs of Natural Systems
Researcher (PI) Alain Burgisser
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE8, ERC-2007-StG
Summary Active volcanoes emit high temperature gases that modify the chemical composition of the Earth’s atmosphere. It is crucial to be able to quantify the contribution of volcanogenic gases to the atmosphere so that the global atmospheric effects of a major eruption can be predicted and so that volcanogenic effects can be discriminated from anthropogenic emissions. At the scale of one volcano, monitoring of gas plumes is a major tool in volcanic risk management. Volcanologists have long measured gas composition and fluxes between and during eruptions and often noted a decoupling between degassing flux and magmatic flux. In parallel, experimental petrologists are now able to calculate the gas composition that is in equilibrium with the magma at depth. However, when the calculated gas composition is compared to that measured at the surface, a general disagreement arises. As a result, it is currently impossible to determine whether a plume is generated in response to passive degassing or to magma ascent. This is a serious drawback as these processes have opposite implications for volcanic activity. Such difficulties are mainly due to the fact that the interplay between degassing mechanisms and gas chemistry has not been addressed. To improve the application of volcanic gas analyses to understanding global geochemical budgets and for the mitigation of volcanic risk, we propose to link deep magmatic processes and surface emissions. Our objective is to model the quantity and composition of volcanic gases as a function of the petrology of the magma at depth and the eruptive regime, and compare those calculations with new measures of plumes at active volcanoes. We will achieve this by modeling the chemical kinetics of degassing in volcanic conduits by using a combination of experimental, field, and numerical approaches. We anticipate building a tool linking flux and composition of gases to eruptive regime, thus opening the door to inverse modeling of volcanic gas observations.
Summary
Active volcanoes emit high temperature gases that modify the chemical composition of the Earth’s atmosphere. It is crucial to be able to quantify the contribution of volcanogenic gases to the atmosphere so that the global atmospheric effects of a major eruption can be predicted and so that volcanogenic effects can be discriminated from anthropogenic emissions. At the scale of one volcano, monitoring of gas plumes is a major tool in volcanic risk management. Volcanologists have long measured gas composition and fluxes between and during eruptions and often noted a decoupling between degassing flux and magmatic flux. In parallel, experimental petrologists are now able to calculate the gas composition that is in equilibrium with the magma at depth. However, when the calculated gas composition is compared to that measured at the surface, a general disagreement arises. As a result, it is currently impossible to determine whether a plume is generated in response to passive degassing or to magma ascent. This is a serious drawback as these processes have opposite implications for volcanic activity. Such difficulties are mainly due to the fact that the interplay between degassing mechanisms and gas chemistry has not been addressed. To improve the application of volcanic gas analyses to understanding global geochemical budgets and for the mitigation of volcanic risk, we propose to link deep magmatic processes and surface emissions. Our objective is to model the quantity and composition of volcanic gases as a function of the petrology of the magma at depth and the eruptive regime, and compare those calculations with new measures of plumes at active volcanoes. We will achieve this by modeling the chemical kinetics of degassing in volcanic conduits by using a combination of experimental, field, and numerical approaches. We anticipate building a tool linking flux and composition of gases to eruptive regime, thus opening the door to inverse modeling of volcanic gas observations.
Max ERC Funding
1 364 478 €
Duration
Start date: 2008-09-01, End date: 2012-12-31
Project acronym DENOVO
Project Detection and interpretation of de novo mutations and structural genomic variations in mental retardation
Researcher (PI) Joris Andre Veltman
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Starting Grant (StG), LS2, ERC-2011-StG_20101109
Summary Mental retardation, like most common neurodevelopmental and psychiatric diseases, shows a strong genetic component, but these underlying genetic causes remain largely unknown. For a long time it was hypothesized that these kind of common diseases are mainly caused by common inherited genetic variants with reduced penetrance. In contrast to this common variant-common disease hypothesis, I here hypothesize that a large proportion of this so-called “missing heritability” for conditions such as mental retardation, schizophrenia, and autism lies in de novo genetic variation that is rapidly eliminated from the population because individuals with such diseases have severely compromised fecundity.
My previous work using microarrays has already demonstrated de novo genomic copy number variations in mental retardation and in schizophrenia. However, microarrays do not allow us to capture the most common form of de novo mutations, those occurring at the nucleotide level. Technological innovations now for the first time allow us to comprehensively study the entire genome of an individual for genomic variations at all levels. In this project I will explore the de novo mutation hypothesis in whole exome and whole genome sequence data from patients with mental retardation. I will optimize and apply whole genome sequencing strategies using patient-parent trios, both in rare mental retardation syndromes as well as common forms of mental retardation. Guidelines for pathogenicity will be established by computational studies aimed at unraveling genotype-phenotype correlations in these family-based genome sequence type datasets.
This project will contribute significantly to resolving the genetic causes of reproductively lethal disorders such as mental retardation, provide critical knowledge on the frequency and consequences of de novo mutations in our genome and help to establish medical genome sequencing as a routine diagnostic approach.
Summary
Mental retardation, like most common neurodevelopmental and psychiatric diseases, shows a strong genetic component, but these underlying genetic causes remain largely unknown. For a long time it was hypothesized that these kind of common diseases are mainly caused by common inherited genetic variants with reduced penetrance. In contrast to this common variant-common disease hypothesis, I here hypothesize that a large proportion of this so-called “missing heritability” for conditions such as mental retardation, schizophrenia, and autism lies in de novo genetic variation that is rapidly eliminated from the population because individuals with such diseases have severely compromised fecundity.
My previous work using microarrays has already demonstrated de novo genomic copy number variations in mental retardation and in schizophrenia. However, microarrays do not allow us to capture the most common form of de novo mutations, those occurring at the nucleotide level. Technological innovations now for the first time allow us to comprehensively study the entire genome of an individual for genomic variations at all levels. In this project I will explore the de novo mutation hypothesis in whole exome and whole genome sequence data from patients with mental retardation. I will optimize and apply whole genome sequencing strategies using patient-parent trios, both in rare mental retardation syndromes as well as common forms of mental retardation. Guidelines for pathogenicity will be established by computational studies aimed at unraveling genotype-phenotype correlations in these family-based genome sequence type datasets.
This project will contribute significantly to resolving the genetic causes of reproductively lethal disorders such as mental retardation, provide critical knowledge on the frequency and consequences of de novo mutations in our genome and help to establish medical genome sequencing as a routine diagnostic approach.
Max ERC Funding
1 499 154 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym DEPICT
Project Design principles and controllability of protein circuits
Researcher (PI) Uri Alon
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), LS2, ERC-2009-AdG
Summary Cells use circuits of interacting proteins to respond to their environment. In the past decades, molecular biology has provided detailed knowledge on the proteins in these circuits and their interactions. To fully understand circuit function requires, in addition to molecular knowledge, new concepts that explain how multiple components work together to perform systems level functions. Our lab has been a leader in defining such concepts, based on combined experimental and theoretical study of well characterized circuits in bacteria and human cells. In this proposal we aim to find novel principles on how circuits resist fluctuations and errors, and how they can be controlled by drugs: (1) Why do key regulatory systems use bifunctional enzymes that catalyze antagonistic reactions (e.g. both kinase and phosphatase)? We will test the role of bifunctional enzymes in making circuits robust to variations in protein levels. (2) Why are some genes regulated by a repressor and others by an activator? We will test this in the context of reduction of errors in transcription control. (3) Are there principles that describe how drugs combine to affect protein dynamics in human cells? We will use a novel dynamic proteomics approach developed in our lab to explore how protein dynamics can be controlled by drug combinations. This research will define principles that unite our understanding of seemingly distinct biological systems, and explain their particular design in terms of systems-level functions. This understanding will help form the basis for a future medicine that rationally controls the state of the cell based on a detailed blueprint of their circuit design, and quantitative principles for the effects of drugs on this circuitry.
Summary
Cells use circuits of interacting proteins to respond to their environment. In the past decades, molecular biology has provided detailed knowledge on the proteins in these circuits and their interactions. To fully understand circuit function requires, in addition to molecular knowledge, new concepts that explain how multiple components work together to perform systems level functions. Our lab has been a leader in defining such concepts, based on combined experimental and theoretical study of well characterized circuits in bacteria and human cells. In this proposal we aim to find novel principles on how circuits resist fluctuations and errors, and how they can be controlled by drugs: (1) Why do key regulatory systems use bifunctional enzymes that catalyze antagonistic reactions (e.g. both kinase and phosphatase)? We will test the role of bifunctional enzymes in making circuits robust to variations in protein levels. (2) Why are some genes regulated by a repressor and others by an activator? We will test this in the context of reduction of errors in transcription control. (3) Are there principles that describe how drugs combine to affect protein dynamics in human cells? We will use a novel dynamic proteomics approach developed in our lab to explore how protein dynamics can be controlled by drug combinations. This research will define principles that unite our understanding of seemingly distinct biological systems, and explain their particular design in terms of systems-level functions. This understanding will help form the basis for a future medicine that rationally controls the state of the cell based on a detailed blueprint of their circuit design, and quantitative principles for the effects of drugs on this circuitry.
Max ERC Funding
2 261 440 €
Duration
Start date: 2010-03-01, End date: 2015-02-28