Project acronym ANISOGEL
Project Injectable anisotropic microgel-in-hydrogel matrices for spinal cord repair
Researcher (PI) Laura De Laporte
Host Institution (HI) DWI LEIBNIZ-INSTITUT FUR INTERAKTIVE MATERIALIEN EV
Call Details Starting Grant (StG), PE8, ERC-2014-STG
Summary This project will engineer an injectable biomaterial that forms an anisotropic microheterogeneous structure in vivo. Injectable hydrogels enable a minimal invasive in situ generation of matrices for the regeneration of tissues and organs, but currently lack structural organization and unidirectional orientation. The anisotropic, injectable hydrogels to be developed will mimic local extracellular matrix architectures that cells encounter in complex tissues (e.g. nerves, muscles). This project aims for the development of a biomimetic scaffold for spinal cord regeneration.
To realize such a major breakthrough, my group will focus on three research objectives. i) Poly(ethylene glycol) microgel-in-hydrogel matrices will be fabricated with the ability to create macroscopic order due to microgel shape anisotropy and magnetic alignment. Barrel-like microgels will be prepared using an in-mold polymerization technique. Their ability to self-assemble will be investigated in function of their dimensions, aspect ratio, crosslinking density, and volume fraction. Superparamagnetic nanoparticles will be included into the microgels to enable unidirectional orientation by means of a magnetic field. Subsequently, the oriented microgels will be interlocked within a master hydrogel. ii) The microgel-in-hydrogel matrices will be equipped with (bio)functional properties for spinal cord regeneration, i.e., to control and optimize mechanical anisotropy and biological signaling by in vitro cell growth experiments. iii) Selected hydrogel composites will be injected after rat spinal cord injury and directional tissue growth and animal functional behavior will be analyzed.
Succesful fabrication of the proposed microgel-in-hydrogel matrix will provide a new type of biomaterial, which enables investigating the effect of an anisotropic structure on physiological and pathological processes in vivo. This is a decisive step towards creating a clinical healing matrix for anisotropic tissue repair.
Summary
This project will engineer an injectable biomaterial that forms an anisotropic microheterogeneous structure in vivo. Injectable hydrogels enable a minimal invasive in situ generation of matrices for the regeneration of tissues and organs, but currently lack structural organization and unidirectional orientation. The anisotropic, injectable hydrogels to be developed will mimic local extracellular matrix architectures that cells encounter in complex tissues (e.g. nerves, muscles). This project aims for the development of a biomimetic scaffold for spinal cord regeneration.
To realize such a major breakthrough, my group will focus on three research objectives. i) Poly(ethylene glycol) microgel-in-hydrogel matrices will be fabricated with the ability to create macroscopic order due to microgel shape anisotropy and magnetic alignment. Barrel-like microgels will be prepared using an in-mold polymerization technique. Their ability to self-assemble will be investigated in function of their dimensions, aspect ratio, crosslinking density, and volume fraction. Superparamagnetic nanoparticles will be included into the microgels to enable unidirectional orientation by means of a magnetic field. Subsequently, the oriented microgels will be interlocked within a master hydrogel. ii) The microgel-in-hydrogel matrices will be equipped with (bio)functional properties for spinal cord regeneration, i.e., to control and optimize mechanical anisotropy and biological signaling by in vitro cell growth experiments. iii) Selected hydrogel composites will be injected after rat spinal cord injury and directional tissue growth and animal functional behavior will be analyzed.
Succesful fabrication of the proposed microgel-in-hydrogel matrix will provide a new type of biomaterial, which enables investigating the effect of an anisotropic structure on physiological and pathological processes in vivo. This is a decisive step towards creating a clinical healing matrix for anisotropic tissue repair.
Max ERC Funding
1 435 396 €
Duration
Start date: 2015-03-01, End date: 2020-02-29
Project acronym CVI_ADAPT
Project Unraveling the history of adaptation in an island model: Cape Verde Arabidopsis
Researcher (PI) Angela Hancock
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Starting Grant (StG), LS8, ERC-2014-STG
Summary Islands have played a pivotal role in evolutionary theory since Darwin and Wallace. Due to their isolation, they represent natural laboratories, providing uncomplicated microcosms where fundamental principles of the evolutionary process can be revealed. One area where island systems can provide a crucial advance is in evolutionary genetics. Here, a primary goal is to reconstruct the mechanisms, mode and tempo of the evolutionary process by identifying specific adaptive functional variants and studying the historical dynamics of these in nature. However, even with recent advances in tools and technologies (e.g., affordable genome-wide sequencing, developments in genome manipulation), the complexity of most natural systems makes this a challenging task.
The proposed research launches a program that employs a unique set of thale cress (Arabidopsis) samples from intriguing populations at the edge of the species range (Cape Verde Islands) to comprehensively characterize the adaptive process in a tractable and ecologically relevant island system. This collection represents the first population sample from this region, where a single individual was collected 30 years ago and has long been an enigma due to its remarkable phenotypic and genetic divergence. We will combine field monitoring, population genetic analyses, trait mapping, powerful new genome editing technology (CRISPR), and spatially explicit modeling to reconstruct the history of the adaptive process in exceptional detail. Moreover, synthesizing our results in the context of biological networks will provide the opportunity to decipher how epistasis and pleiotropy impacted adaptive trajectories. By applying the wealth of tools available in Arabidopsis thaliana to this intriguing natural population, we will uncover general principles of adaptation and produce a roadmap and toolkit for future research in diverse systems to predict outcomes of environmental fluctuations and longer-term changes.
Summary
Islands have played a pivotal role in evolutionary theory since Darwin and Wallace. Due to their isolation, they represent natural laboratories, providing uncomplicated microcosms where fundamental principles of the evolutionary process can be revealed. One area where island systems can provide a crucial advance is in evolutionary genetics. Here, a primary goal is to reconstruct the mechanisms, mode and tempo of the evolutionary process by identifying specific adaptive functional variants and studying the historical dynamics of these in nature. However, even with recent advances in tools and technologies (e.g., affordable genome-wide sequencing, developments in genome manipulation), the complexity of most natural systems makes this a challenging task.
The proposed research launches a program that employs a unique set of thale cress (Arabidopsis) samples from intriguing populations at the edge of the species range (Cape Verde Islands) to comprehensively characterize the adaptive process in a tractable and ecologically relevant island system. This collection represents the first population sample from this region, where a single individual was collected 30 years ago and has long been an enigma due to its remarkable phenotypic and genetic divergence. We will combine field monitoring, population genetic analyses, trait mapping, powerful new genome editing technology (CRISPR), and spatially explicit modeling to reconstruct the history of the adaptive process in exceptional detail. Moreover, synthesizing our results in the context of biological networks will provide the opportunity to decipher how epistasis and pleiotropy impacted adaptive trajectories. By applying the wealth of tools available in Arabidopsis thaliana to this intriguing natural population, we will uncover general principles of adaptation and produce a roadmap and toolkit for future research in diverse systems to predict outcomes of environmental fluctuations and longer-term changes.
Max ERC Funding
1 609 375 €
Duration
Start date: 2015-11-01, End date: 2020-10-31
Project acronym HybridMiX
Project Genetic Mapping of Evolutionary Developmental Variation using Hybrid Mouse in vitro Crosses
Researcher (PI) Yingguang Frank Chan
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Starting Grant (StG), LS8, ERC-2014-STG
Summary Discovering the genetic changes underlying species differences is a central goal in evolutionary genetics. Most evolutionarily important traits affecting fitness are complex or quantitative traits, whose genetic bases are elusive. In mammals, dissecting the genetic basis of complex trait variation is particularly challenging, because efficient genetic mapping requires enormous pedigrees or specialized genetic panels that are typically beyond the resources of individual groups. Using a radically novel method to circumvent breeding limitations by “breeding” mice in vitro, I propose to dissect the genetic basis of evolutionary developmental variation. This ground-breaking approach will allow me to create large genetic mapping panels of potentially any size from mouse interspecific hybrids of increasing evolutionary divergence. In vitro crosses promise a breakthrough in evolutionary biology: by bypassing hybrid sterility and inviability, we will ask which genetic changes underlie species differences. The proposed experiments address how genetic changes accumulate during evolution of new species to shape gene regulatory networks and cause phenotypic changes at the gene expression, fitness and organismal level. This research has the potential to revolutionize genetic mapping. If realized, its impact on personalized medicine, agricultural science and evolutionary research cannot be understated.
Summary
Discovering the genetic changes underlying species differences is a central goal in evolutionary genetics. Most evolutionarily important traits affecting fitness are complex or quantitative traits, whose genetic bases are elusive. In mammals, dissecting the genetic basis of complex trait variation is particularly challenging, because efficient genetic mapping requires enormous pedigrees or specialized genetic panels that are typically beyond the resources of individual groups. Using a radically novel method to circumvent breeding limitations by “breeding” mice in vitro, I propose to dissect the genetic basis of evolutionary developmental variation. This ground-breaking approach will allow me to create large genetic mapping panels of potentially any size from mouse interspecific hybrids of increasing evolutionary divergence. In vitro crosses promise a breakthrough in evolutionary biology: by bypassing hybrid sterility and inviability, we will ask which genetic changes underlie species differences. The proposed experiments address how genetic changes accumulate during evolution of new species to shape gene regulatory networks and cause phenotypic changes at the gene expression, fitness and organismal level. This research has the potential to revolutionize genetic mapping. If realized, its impact on personalized medicine, agricultural science and evolutionary research cannot be understated.
Max ERC Funding
1 499 923 €
Duration
Start date: 2015-08-01, End date: 2020-07-31
Project acronym HyMoCo
Project Hybrid Node Modes for Highly Efficient Light Concentrators
Researcher (PI) Patrick Görrn
Host Institution (HI) BERGISCHE UNIVERSITAET WUPPERTAL
Call Details Starting Grant (StG), PE8, ERC-2014-STG
Summary The meaning of solar energy for future decentralized power supply will largely depend on both efficiency and cost of solar to electrical power conversion. All kinds of conversion strategies including photovoltaics, concentrated solar power, solar to fuel and others would benefit from efficiently collecting solar power on large areas. For this reason luminescent solar concentrators have been developed for over thirty years, but due to waveguide losses their maximum size is still limited to a few centimeters.
The proposed project suggests the exploitation of a new type of electromagnetic waveguide in order to realize passive planar concentrators of unsurpassed collection efficiency, size, concentration, lifetime and costs.
A dielectric TE1-mode shows a node, a position in the waveguide where no intensity is found. A thin film placed in this node remains largely “invisible” for the propagating mode. Such dielectric node modes (DNMs) have been investigated by the applicant in previous work, but only recently a silver island film (SIF) was for the first time placed in such a node. The resulting extremely low waveguide losses cannot be explained by our current understanding of waveguide modes and hint to a hybridization between the SIF-bound long-range surface plasmon polaritons (LRSPPs) and the DNMs into what we call hybrid node modes (HNMs).
The SIFs strongly interact with incident light. An appropriate nanopatterning of SIFs enables efficient excitation of low-loss HNMs modes collecting solar power over square meters and concentrating it. To achieve this goal new technological methods are used that enable patterning on the nanometer scale and low cost roll-to-roll processing at the same time. New measurement techniques and numerical simulation tools will be developed to investigate the HNMs – a novel kind of electromagnetic modes – and their exploitation in the passive solar concentrators.
Summary
The meaning of solar energy for future decentralized power supply will largely depend on both efficiency and cost of solar to electrical power conversion. All kinds of conversion strategies including photovoltaics, concentrated solar power, solar to fuel and others would benefit from efficiently collecting solar power on large areas. For this reason luminescent solar concentrators have been developed for over thirty years, but due to waveguide losses their maximum size is still limited to a few centimeters.
The proposed project suggests the exploitation of a new type of electromagnetic waveguide in order to realize passive planar concentrators of unsurpassed collection efficiency, size, concentration, lifetime and costs.
A dielectric TE1-mode shows a node, a position in the waveguide where no intensity is found. A thin film placed in this node remains largely “invisible” for the propagating mode. Such dielectric node modes (DNMs) have been investigated by the applicant in previous work, but only recently a silver island film (SIF) was for the first time placed in such a node. The resulting extremely low waveguide losses cannot be explained by our current understanding of waveguide modes and hint to a hybridization between the SIF-bound long-range surface plasmon polaritons (LRSPPs) and the DNMs into what we call hybrid node modes (HNMs).
The SIFs strongly interact with incident light. An appropriate nanopatterning of SIFs enables efficient excitation of low-loss HNMs modes collecting solar power over square meters and concentrating it. To achieve this goal new technological methods are used that enable patterning on the nanometer scale and low cost roll-to-roll processing at the same time. New measurement techniques and numerical simulation tools will be developed to investigate the HNMs – a novel kind of electromagnetic modes – and their exploitation in the passive solar concentrators.
Max ERC Funding
1 485 000 €
Duration
Start date: 2015-03-01, End date: 2020-02-29
Project acronym Inhomogeneities
Project Micro-scale inhomogeneities in compressed systems and their impact onto the PROCESS- functioning-chain and the PRODUCT-characteristics
Researcher (PI) Andreas Braeuer
Host Institution (HI) TECHNISCHE UNIVERSITAET BERGAKADEMIE FREIBERG
Call Details Starting Grant (StG), PE8, ERC-2014-STG
Summary Compressed fluid systems handled in high pressure processes feature diffusivities smaller than the kinematic viscosity. Therefore during mixing the lifetime of micro(µ)-scale(s) inhomogeneities exceeds that one of macro(m)-scale(s) inhomogeneities. Thus m-s homogeneous systems can still exhibit µ-s inhomogeneities. They affect the functioning-chain of processes, e.g. reactions and phase-transitions or –separations, which themselves also take place on a sub-macro-scale.
Therefore it will be analyzed in situ how µ-s inhomogeneities influence the functioning chain of the particle generation (supercritical antisolvent technology), the reaction (high pressure combustion), and the phase-separation or phase-transition mechanisms (surfactant-free CO2-based micro-emulsions and gas hydrates) and to which extend these inhomogeneities are responsible for the characteristics of the product, such as unfavourable size distributions of particulate products and/or pollutant emissions.
On this purpose the here proposed and self-developed non-invasive and in situ Raman spectroscopic technique considers the INTENSITY-ratios of Raman signals to analyze the m-s composition and the SIGNATURE of the OH stretch vibration Raman signal of water (or alcohols) to analyze the µ-s composition of fluid mixtures. The SIGNATURE of the OH stretch vibration Raman signal is influenced by the development of the hydrogen bonds -an intermolecular interaction- and thus provides the µ-s composition, though the probe volume of the Raman sensor is m-s. The signal-INTENSITY-ratio and signal-SIGNATURE are extracted both from one and the same “m-s” Raman spectrum of the mixture. This allows the comparison of the degree of mixing on m-s and µ-s simultaneously, and enables the analysis of whether a system at any instance of mixing (instance of the onset of a reaction or a phase transition or –separation) has reached the favourable µ-s homogeneity, which would result in homogeneous and uniform products.
Summary
Compressed fluid systems handled in high pressure processes feature diffusivities smaller than the kinematic viscosity. Therefore during mixing the lifetime of micro(µ)-scale(s) inhomogeneities exceeds that one of macro(m)-scale(s) inhomogeneities. Thus m-s homogeneous systems can still exhibit µ-s inhomogeneities. They affect the functioning-chain of processes, e.g. reactions and phase-transitions or –separations, which themselves also take place on a sub-macro-scale.
Therefore it will be analyzed in situ how µ-s inhomogeneities influence the functioning chain of the particle generation (supercritical antisolvent technology), the reaction (high pressure combustion), and the phase-separation or phase-transition mechanisms (surfactant-free CO2-based micro-emulsions and gas hydrates) and to which extend these inhomogeneities are responsible for the characteristics of the product, such as unfavourable size distributions of particulate products and/or pollutant emissions.
On this purpose the here proposed and self-developed non-invasive and in situ Raman spectroscopic technique considers the INTENSITY-ratios of Raman signals to analyze the m-s composition and the SIGNATURE of the OH stretch vibration Raman signal of water (or alcohols) to analyze the µ-s composition of fluid mixtures. The SIGNATURE of the OH stretch vibration Raman signal is influenced by the development of the hydrogen bonds -an intermolecular interaction- and thus provides the µ-s composition, though the probe volume of the Raman sensor is m-s. The signal-INTENSITY-ratio and signal-SIGNATURE are extracted both from one and the same “m-s” Raman spectrum of the mixture. This allows the comparison of the degree of mixing on m-s and µ-s simultaneously, and enables the analysis of whether a system at any instance of mixing (instance of the onset of a reaction or a phase transition or –separation) has reached the favourable µ-s homogeneity, which would result in homogeneous and uniform products.
Max ERC Funding
1 943 750 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym TIME-BRIDGE
Project Time-scale bridging potentials for realistic molecular dynamics simulations
Researcher (PI) Blazej Tadeusz Grabowski
Host Institution (HI) MAX PLANCK INSTITUT FUR EISENFORSCHUNG GMBH
Call Details Starting Grant (StG), PE8, ERC-2014-STG
Summary The possibility to produce materials with ultra-strengths could revolutionize materials design. Since 80 years ultra-strength materials are known to exist only theoretically. Now, new experiments show that traditional believe can be overcome by nanostructured design. Yet, while selected experiments point towards this scientifically fascinating and technologically important possibility (e.g., for advances in structural and functional materials), further progress crucially relies on insight from theoretical simulations. The most successful simulation tool is molecular dynamics. Recent advances in hardware allow to tackle trillions of atoms making a comparison with nano-experiments almost possible. The nagging problem is, however, a huge time-scale gap of up to ten orders of magnitude and none of the presently available approaches is able to cope with this discrepancy.
TIME-BRIDGE aims at solving the time-scale problem by borrowing a concept well known and developed in the field of first-principles simulations: the pseudopotential ansatz. In first principles simulations a similar time scale gap exists between slow and fast moving electrons. The solution is to capture the effect of the fast electrons only effectively within a pseudopotential while retaining the motion of slow electrons important for chemical bonding. An equivalent pseudopotential ansatz is envisioned to be applicable to the fast thermal motion of atoms, the origin of the time scale problem. Capturing the thermal motion in an effective potential will allow to simulate the relevant mechanical processes occurring on microsecond and second time scales. In TIME-BRIDGE high risk and high gains apply: the physics of electrons is distinct from the atomic motion possibly making the pseudopotential ansatz non-transferable, but—based on PI’s distinguished expertise and his recent methodological advancements—a route to bridge the fundamental time scale gap might arise.
Summary
The possibility to produce materials with ultra-strengths could revolutionize materials design. Since 80 years ultra-strength materials are known to exist only theoretically. Now, new experiments show that traditional believe can be overcome by nanostructured design. Yet, while selected experiments point towards this scientifically fascinating and technologically important possibility (e.g., for advances in structural and functional materials), further progress crucially relies on insight from theoretical simulations. The most successful simulation tool is molecular dynamics. Recent advances in hardware allow to tackle trillions of atoms making a comparison with nano-experiments almost possible. The nagging problem is, however, a huge time-scale gap of up to ten orders of magnitude and none of the presently available approaches is able to cope with this discrepancy.
TIME-BRIDGE aims at solving the time-scale problem by borrowing a concept well known and developed in the field of first-principles simulations: the pseudopotential ansatz. In first principles simulations a similar time scale gap exists between slow and fast moving electrons. The solution is to capture the effect of the fast electrons only effectively within a pseudopotential while retaining the motion of slow electrons important for chemical bonding. An equivalent pseudopotential ansatz is envisioned to be applicable to the fast thermal motion of atoms, the origin of the time scale problem. Capturing the thermal motion in an effective potential will allow to simulate the relevant mechanical processes occurring on microsecond and second time scales. In TIME-BRIDGE high risk and high gains apply: the physics of electrons is distinct from the atomic motion possibly making the pseudopotential ansatz non-transferable, but—based on PI’s distinguished expertise and his recent methodological advancements—a route to bridge the fundamental time scale gap might arise.
Max ERC Funding
1 499 375 €
Duration
Start date: 2015-07-01, End date: 2020-06-30
