Project acronym AFFINITY
Project Actuation of Ferromagnetic Fibre Networks to improve Implant Longevity
Researcher (PI) Athina Markaki
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), PE8, ERC-2009-StG
Summary This proposal is for an exploratory study into a radical new approach to the problem of orthopaedic implant loosening. Such loosening commonly occurs because the joint between the implant and the surrounding bone is insufficiently strong and durable. It is a serious problem both for implants cemented to the bone and for those dependent on bone in-growth into a rough/porous implant surface. In the latter case, the main problem is commonly that bone in-growth is insufficiently rapid or deep for a strong bond to be established. The idea proposed in this work is that the implant should have a highly porous surface layer, made by bonding ferromagnetic fibres together, into which bone tissue growth would occur. During the post-operative period, application of a magnetic field will cause the fibre network to deform elastically, as individual fibres tend to align with the field. This will impose strains on the bone tissue as it grows into the fibre network. Such mechanical deformation is known to be highly beneficial in promoting bone growth, providing the associated strain lies in a certain range (~0.1%). Preliminary work, involving both model development and experimental studies on the effect of magnetic fields on fibre networks, has suggested that beneficial therapeutic effects can be induced using field strengths no greater than those already employed for diagnostic purposes. A comprehensive 5-year, highly inter-disciplinary programme is planned, encompassing processing, network architecture characterisation, magneto-mechanical response investigations, various modelling activities and systematic in vitro experimentation to establish whether magneto-mechanical Actuation of Ferromagnetic Fibre Networks shows promise as a new therapeutic approach to improve implant longevity.
Summary
This proposal is for an exploratory study into a radical new approach to the problem of orthopaedic implant loosening. Such loosening commonly occurs because the joint between the implant and the surrounding bone is insufficiently strong and durable. It is a serious problem both for implants cemented to the bone and for those dependent on bone in-growth into a rough/porous implant surface. In the latter case, the main problem is commonly that bone in-growth is insufficiently rapid or deep for a strong bond to be established. The idea proposed in this work is that the implant should have a highly porous surface layer, made by bonding ferromagnetic fibres together, into which bone tissue growth would occur. During the post-operative period, application of a magnetic field will cause the fibre network to deform elastically, as individual fibres tend to align with the field. This will impose strains on the bone tissue as it grows into the fibre network. Such mechanical deformation is known to be highly beneficial in promoting bone growth, providing the associated strain lies in a certain range (~0.1%). Preliminary work, involving both model development and experimental studies on the effect of magnetic fields on fibre networks, has suggested that beneficial therapeutic effects can be induced using field strengths no greater than those already employed for diagnostic purposes. A comprehensive 5-year, highly inter-disciplinary programme is planned, encompassing processing, network architecture characterisation, magneto-mechanical response investigations, various modelling activities and systematic in vitro experimentation to establish whether magneto-mechanical Actuation of Ferromagnetic Fibre Networks shows promise as a new therapeutic approach to improve implant longevity.
Max ERC Funding
1 442 756 €
Duration
Start date: 2010-01-01, End date: 2015-11-30
Project acronym CARNIVOROM
Project Molecular basis of carnivory Excitability, movement, and endocrinology of plant traps
Researcher (PI) Rainer Franz Hedrich
Host Institution (HI) JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Call Details Advanced Grant (AdG), LS9, ERC-2009-AdG
Summary Predation plays a major role in energy and nutrient flow in the biological food chain. Carnivory is best known from the animal kingdom, but the plant kingdom has flesh eaters as well. This field has attracted much interest since Darwin s time, but many fundamental properties of the carnivorous life style remain largely unexplored. This project will close this gap by a multidisciplinary approach based on state-of-art bioinformatics, molecular biology, chemistry and biophysics. It will focus on 1. Genome/Transcriptome Profiling to study the genetic make-up of carnivorous plants (CPs) and the evolution of carnivory 2. Origin of Excitability to investigate whether CPs gained the inventory to fire action potentials from captured animals or rather evolved excitability independently 3. Prey Recognition on the basis of mechanical- and chemical senses 4. Endocrinology Structure and function of exocrine glands - CPs offer a unique system to study the biology of digestive glands (exo-/endocytosis) in plants. Over 600 plant species use special structures to capture animals such as insects. The genome/transcriptome of major trap types such as snap traps, tentacles traps, suction traps, corkscrew traps, and pitfall traps will be compared and trap-specific genes identified. Among them those giving rise to membrane excitation, excitation-contraction coupling and exocrine systems (glands) will be functionally characterized in detail. Using loss-of-function mutants and transformed plants with respect to CP-specific the role of CP-specific in electrical signalling, excitation contraction coupling, and excretion will be unravelled. The evolution of electrical activity and carnivory of plants is worth being examined not only for its importance in general, but also as a model for understanding the evolution of the human nervous and endocrine system.
Summary
Predation plays a major role in energy and nutrient flow in the biological food chain. Carnivory is best known from the animal kingdom, but the plant kingdom has flesh eaters as well. This field has attracted much interest since Darwin s time, but many fundamental properties of the carnivorous life style remain largely unexplored. This project will close this gap by a multidisciplinary approach based on state-of-art bioinformatics, molecular biology, chemistry and biophysics. It will focus on 1. Genome/Transcriptome Profiling to study the genetic make-up of carnivorous plants (CPs) and the evolution of carnivory 2. Origin of Excitability to investigate whether CPs gained the inventory to fire action potentials from captured animals or rather evolved excitability independently 3. Prey Recognition on the basis of mechanical- and chemical senses 4. Endocrinology Structure and function of exocrine glands - CPs offer a unique system to study the biology of digestive glands (exo-/endocytosis) in plants. Over 600 plant species use special structures to capture animals such as insects. The genome/transcriptome of major trap types such as snap traps, tentacles traps, suction traps, corkscrew traps, and pitfall traps will be compared and trap-specific genes identified. Among them those giving rise to membrane excitation, excitation-contraction coupling and exocrine systems (glands) will be functionally characterized in detail. Using loss-of-function mutants and transformed plants with respect to CP-specific the role of CP-specific in electrical signalling, excitation contraction coupling, and excretion will be unravelled. The evolution of electrical activity and carnivory of plants is worth being examined not only for its importance in general, but also as a model for understanding the evolution of the human nervous and endocrine system.
Max ERC Funding
2 481 057 €
Duration
Start date: 2010-03-01, End date: 2015-02-28
Project acronym CIF
Project Complex Interfacial Flows: From the Nano- to the Macro-Scale
Researcher (PI) Serafim Kalliadasis
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Advanced Grant (AdG), PE8, ERC-2009-AdG
Summary A wide variety of natural phenomena and technological applications involve flow, transport and chemical reactions taking place on or near fluid-solid or fluid-fluid interfaces. From gravity currents under water and lava flows to heat and mass transport processes in engineering applications and to the rapidly developing field of microfluidics. Both equilibrium properties of a fluid and transportcoefficients are modified in the vicinity of interfaces. The effect of these changes is crucial in the behavior of ultra-thin fluidfilms and fluid motion in microchannels of micro-electromechanical systems, but is essential as well in macroscopic phenomena involving interfacial singularities, such as thin-film rupture and motion of three-phase contact lines associated e.g. with droplet spreading. Interface boundaries are mesoscopic structures. While material properties vary smoothly at macroscopic distances from an interface, gradients in the normal direction of conserved parameters, such as density, are steep with strong variations as the molecular scale in the neighborhood of the interface is approached. This brings about a contradiction between the need in macroscopic description and a necessity to take into consideration microscopic factors that come to influence the fluid motion and transport on incommensurately larger scales. The aim of the proposed research is to develop a class of novel continuous models bridging the gap between molecular dynamics and conventional hydrodynamics and applicable at mesoscopic distances from gas-liquid and fluid-solid interfaces. A combination of analytical techniques, numerical modeling and computer-aided multiscale analysis will be employed. The results of the proposed work will greatly contribute to the fundamental understanding of mesoscopic non-equilibrium phenomena in the vicinity of interfaces and to the development of novel computational methods combining the advantages of molecular and continuous models.
Summary
A wide variety of natural phenomena and technological applications involve flow, transport and chemical reactions taking place on or near fluid-solid or fluid-fluid interfaces. From gravity currents under water and lava flows to heat and mass transport processes in engineering applications and to the rapidly developing field of microfluidics. Both equilibrium properties of a fluid and transportcoefficients are modified in the vicinity of interfaces. The effect of these changes is crucial in the behavior of ultra-thin fluidfilms and fluid motion in microchannels of micro-electromechanical systems, but is essential as well in macroscopic phenomena involving interfacial singularities, such as thin-film rupture and motion of three-phase contact lines associated e.g. with droplet spreading. Interface boundaries are mesoscopic structures. While material properties vary smoothly at macroscopic distances from an interface, gradients in the normal direction of conserved parameters, such as density, are steep with strong variations as the molecular scale in the neighborhood of the interface is approached. This brings about a contradiction between the need in macroscopic description and a necessity to take into consideration microscopic factors that come to influence the fluid motion and transport on incommensurately larger scales. The aim of the proposed research is to develop a class of novel continuous models bridging the gap between molecular dynamics and conventional hydrodynamics and applicable at mesoscopic distances from gas-liquid and fluid-solid interfaces. A combination of analytical techniques, numerical modeling and computer-aided multiscale analysis will be employed. The results of the proposed work will greatly contribute to the fundamental understanding of mesoscopic non-equilibrium phenomena in the vicinity of interfaces and to the development of novel computational methods combining the advantages of molecular and continuous models.
Max ERC Funding
1 273 788 €
Duration
Start date: 2010-04-01, End date: 2016-03-31
Project acronym COCOON
Project Conformal coating of nanoporous materials
Researcher (PI) Christophe Detavernier
Host Institution (HI) UNIVERSITEIT GENT
Call Details Starting Grant (StG), PE8, ERC-2009-StG
Summary CONTEXT - Nanoporous structures are used for application in catalysis, molecular separation, fuel cells, dye sensitized solar cells etc. Given the near molecular size of the porous network, it is extremely challenging to modify the interior surface of the pores after the nanoporous material has been synthesized.
THIS PROPOSAL - Atomic Layer Deposition (ALD) is envisioned as a novel technique for creating catalytically active sites and for controlling the pore size distribution in nanoporous materials. ALD is a self-limited growth method that is characterized by alternating exposure of the growing film to precursor vapours, resulting in the sequential deposition of (sub)monolayers. It provides atomic level control of thickness and composition, and is currently used in micro-electronics to grow films into structures with aspect ratios of up to 100 / 1. We aim to make the fundamental breakthroughs necessary to enable atomic layer deposition to engineer the composition, size and shape of the interior surface of nanoporous materials with aspect ratios in excess of 10,000 / 1.
POTENTIAL IMPACT Achieving these objectives will enable atomic level engineering of the interior surface of any porous material. We plan to focus on three specific applications where our results will have both medium and long term impacts:
- Engineering the composition of pore walls using ALD, e.g. to create catalytic sites (e.g. Al for acid sites, Ti for redox sites, or Pt, Pd or Ni)
- chemical functionalization of the pore walls with atomic level control can result in breakthrough applications in the fields of catalysis and sensors.
- Atomic level control of the size of nanopores through ALD controlling the pore size distribution of molecular sieves can potentially lead to breakthrough applications in molecular separation and filtration.
- Nanocasting replication of a mesoporous template by means of ALD can result in the mass-scale production of nanotubes.
Summary
CONTEXT - Nanoporous structures are used for application in catalysis, molecular separation, fuel cells, dye sensitized solar cells etc. Given the near molecular size of the porous network, it is extremely challenging to modify the interior surface of the pores after the nanoporous material has been synthesized.
THIS PROPOSAL - Atomic Layer Deposition (ALD) is envisioned as a novel technique for creating catalytically active sites and for controlling the pore size distribution in nanoporous materials. ALD is a self-limited growth method that is characterized by alternating exposure of the growing film to precursor vapours, resulting in the sequential deposition of (sub)monolayers. It provides atomic level control of thickness and composition, and is currently used in micro-electronics to grow films into structures with aspect ratios of up to 100 / 1. We aim to make the fundamental breakthroughs necessary to enable atomic layer deposition to engineer the composition, size and shape of the interior surface of nanoporous materials with aspect ratios in excess of 10,000 / 1.
POTENTIAL IMPACT Achieving these objectives will enable atomic level engineering of the interior surface of any porous material. We plan to focus on three specific applications where our results will have both medium and long term impacts:
- Engineering the composition of pore walls using ALD, e.g. to create catalytic sites (e.g. Al for acid sites, Ti for redox sites, or Pt, Pd or Ni)
- chemical functionalization of the pore walls with atomic level control can result in breakthrough applications in the fields of catalysis and sensors.
- Atomic level control of the size of nanopores through ALD controlling the pore size distribution of molecular sieves can potentially lead to breakthrough applications in molecular separation and filtration.
- Nanocasting replication of a mesoporous template by means of ALD can result in the mass-scale production of nanotubes.
Max ERC Funding
1 432 800 €
Duration
Start date: 2010-01-01, End date: 2014-12-31
Project acronym COLLREGEN
Project Collagen scaffolds for bone regeneration: applied biomaterials, bioreactor and stem cell technology
Researcher (PI) Fergal Joseph O'brien
Host Institution (HI) ROYAL COLLEGE OF SURGEONS IN IRELAND
Call Details Starting Grant (StG), PE8, ERC-2009-StG
Summary Regenerative medicine aims to regenerate damaged tissues by developing functional cell, tissue, and organ substitutes to repair, replace or enhance biological function in damaged tissues. The focus of this research programme is to develop bone graft substitute biomaterials and laboratory-engineered bone tissue for implantation in damaged sites. At a simplistic level, biological tissues consist of cells, signalling mechanisms and extracellular matrix. Regenerative medicine/tissue engineering technologies are based on this biological triad and involve the successful interaction between three components: the scaffold that holds the cells together to create the tissues physical form, the cells that create the tissue, and the biological signalling mechanisms (such as growth factors or bioreactors) that direct the cells to express the desired tissue phenotype. The research proposed in this project includes specific projects in all three areas. The programme will be centred on the collagen-based biomaterials developed in the applicant s laboratory and will incorporate cutting edge stem cell technologies, growth factor delivery, gene therapy and bioreactor technology which will translate to in vivo tissue repair. This translational research programme will be divided into four specific themes: (i) development of novel osteoinductive and angiogenic smart scaffolds for bone tissue regeneration, (ii) scaffold and stem cell therapies for bone tissue regeneration, (iii) bone tissue engineering using a flow perfusion bioreactor and (iv) in vivo bone repair using engineered bone and smart scaffolds.
Summary
Regenerative medicine aims to regenerate damaged tissues by developing functional cell, tissue, and organ substitutes to repair, replace or enhance biological function in damaged tissues. The focus of this research programme is to develop bone graft substitute biomaterials and laboratory-engineered bone tissue for implantation in damaged sites. At a simplistic level, biological tissues consist of cells, signalling mechanisms and extracellular matrix. Regenerative medicine/tissue engineering technologies are based on this biological triad and involve the successful interaction between three components: the scaffold that holds the cells together to create the tissues physical form, the cells that create the tissue, and the biological signalling mechanisms (such as growth factors or bioreactors) that direct the cells to express the desired tissue phenotype. The research proposed in this project includes specific projects in all three areas. The programme will be centred on the collagen-based biomaterials developed in the applicant s laboratory and will incorporate cutting edge stem cell technologies, growth factor delivery, gene therapy and bioreactor technology which will translate to in vivo tissue repair. This translational research programme will be divided into four specific themes: (i) development of novel osteoinductive and angiogenic smart scaffolds for bone tissue regeneration, (ii) scaffold and stem cell therapies for bone tissue regeneration, (iii) bone tissue engineering using a flow perfusion bioreactor and (iv) in vivo bone repair using engineered bone and smart scaffolds.
Max ERC Funding
1 999 530 €
Duration
Start date: 2009-11-01, End date: 2015-09-30
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 DELPHINS
Project DESIGN AND ELABORATION OFMULTI-PHYSICS INTEGRATED NANOSYSTEMS
Researcher (PI) Thomas Ernst
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Call Details Starting Grant (StG), PE7, ERC-2009-StG
Summary The innovation of DELPHINS application will consist in building a generic multi-sensor design platform for embedded multi-gas-analysis-on-chip, based on a global modelling from the individual NEMS sensors to a global multiphysics NEMS-CMOS VLSI (Very large Scale Integration) system. The latter constitute a new research field with many potential applications such as in medicine (specific diseases recognition) but also in security (toxic and complex air pollutions), in industry (perfumes, agribusiness) and environment control. As an example, several studies in the last 10 years have demonstrated that some specific combination of biomarkers in breath above a given threshold could indicate early stage of diseases. More generally, patterns of breathing gas could constitute a virtual fingerprint of specific pathologies. NEMS (Nano-Electro-Mechanical Systems) based sensor is one of the most promising technologies to get the required resolutions and sensitivities for few molecules detection. We will focus on the analytical module of the system (sensing part + embedded electronics processing) that will include ultra-dense (more than thousands) NEMS arrays with state-of the art CMOS transistors. We will obtain integrated nano-oscillators individually addressed within an innovative architecture inspired from memory and imaging technologies. Few molecules sensitivity will be achieved thanks to suspended resonant nanowires co-integrated locally with their closed-loop and reading electronics. This would make possible the analysis of complex gases within an integrated portable system, which does not exist yet.
Summary
The innovation of DELPHINS application will consist in building a generic multi-sensor design platform for embedded multi-gas-analysis-on-chip, based on a global modelling from the individual NEMS sensors to a global multiphysics NEMS-CMOS VLSI (Very large Scale Integration) system. The latter constitute a new research field with many potential applications such as in medicine (specific diseases recognition) but also in security (toxic and complex air pollutions), in industry (perfumes, agribusiness) and environment control. As an example, several studies in the last 10 years have demonstrated that some specific combination of biomarkers in breath above a given threshold could indicate early stage of diseases. More generally, patterns of breathing gas could constitute a virtual fingerprint of specific pathologies. NEMS (Nano-Electro-Mechanical Systems) based sensor is one of the most promising technologies to get the required resolutions and sensitivities for few molecules detection. We will focus on the analytical module of the system (sensing part + embedded electronics processing) that will include ultra-dense (more than thousands) NEMS arrays with state-of the art CMOS transistors. We will obtain integrated nano-oscillators individually addressed within an innovative architecture inspired from memory and imaging technologies. Few molecules sensitivity will be achieved thanks to suspended resonant nanowires co-integrated locally with their closed-loop and reading electronics. This would make possible the analysis of complex gases within an integrated portable system, which does not exist yet.
Max ERC Funding
1 723 206 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym DIADRUG
Project Insulin resistance and diabetic nephropathy - development of novel in vivo models for drug discovery
Researcher (PI) Sanna Lehtonen
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Starting Grant (StG), LS9, ERC-2009-StG
Summary Up to one third of diabetic patients develop nephropathy, a serious complication of diabetes. Microalbuminuria is the earliest sign of the complication, which may ultimately develop to end-stage renal disease requiring dialysis or a kidney transplant. Insulin resistance and metabolic syndrome are associated with an increased risk for diabetic nephropathy. Interestingly, glomerular epithelial cells or podocytes have recently been shown to be insulin responsive. Further, nephrin, a key structural component of podocytes, is essential for insulin action in these cells. Our novel findings show that adaptor protein CD2AP, an interaction partner of nephrin, associates with regulators of insulin signaling and glucose transport in glomeruli. The results suggest that nephrin and CD2AP are involved, by association with these proteins, in the regulation of insulin signaling and glucose transport in podocytes. We hypothesize that podocytes can develop insulin resistance and that disturbances in insulin response affect podocyte function and contribute to the development of diabetic nephropathy. The aim of this project is to clarify the mechanisms leading to development of insulin resistance in podocytes and to study the association between insulin resistance and the development of diabetic nephropathy. For this we will develop transgenic zebrafish and mouse models by overexpressing/knocking down insulin signaling-associated proteins specifically in podocytes. Further, we aim to identify novel drug leads to treat insulin resistance and diabetic nephropathy by performing high-throughput small molecule library screens on the developed transgenic fish models. The ultimate goal is to find a treatment to combat the early stages of diabetic nephropathy in humans.
Summary
Up to one third of diabetic patients develop nephropathy, a serious complication of diabetes. Microalbuminuria is the earliest sign of the complication, which may ultimately develop to end-stage renal disease requiring dialysis or a kidney transplant. Insulin resistance and metabolic syndrome are associated with an increased risk for diabetic nephropathy. Interestingly, glomerular epithelial cells or podocytes have recently been shown to be insulin responsive. Further, nephrin, a key structural component of podocytes, is essential for insulin action in these cells. Our novel findings show that adaptor protein CD2AP, an interaction partner of nephrin, associates with regulators of insulin signaling and glucose transport in glomeruli. The results suggest that nephrin and CD2AP are involved, by association with these proteins, in the regulation of insulin signaling and glucose transport in podocytes. We hypothesize that podocytes can develop insulin resistance and that disturbances in insulin response affect podocyte function and contribute to the development of diabetic nephropathy. The aim of this project is to clarify the mechanisms leading to development of insulin resistance in podocytes and to study the association between insulin resistance and the development of diabetic nephropathy. For this we will develop transgenic zebrafish and mouse models by overexpressing/knocking down insulin signaling-associated proteins specifically in podocytes. Further, we aim to identify novel drug leads to treat insulin resistance and diabetic nephropathy by performing high-throughput small molecule library screens on the developed transgenic fish models. The ultimate goal is to find a treatment to combat the early stages of diabetic nephropathy in humans.
Max ERC Funding
2 000 000 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym DOFOCO
Project Do forests cool the Earth? Reconciling sustained productivity and minimum climate response with portfolios of contrasting forest management strategies
Researcher (PI) Sebastiaan Luyssaert
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Call Details Starting Grant (StG), LS9, ERC-2009-StG
Summary Forests, of which globally 70% are managed, play a particularly important role in the global carbon cycle. Recently, forest management became a top priority on the agenda of the political negotiations to mitigate climate change because forest plantations may remove atmospheric CO2 and if used for energy production, the wood is a substitute for fossil fuel. However, this political imperative is at present running well ahead of the science required to deliver it. Despite the key implications of forest management on: 1) the carbon-energy-water balance, and 2) production, recreation and environmental protection, there are no integrated studies of its effects on the Earth s climate. The overall goal of DOFOCO is to quantify and understand the role of forest management in mitigating climate change. Specifically, I want to challenge the current focus on the carbon cycle and replace it with a total climate impact approach. Hence, the whole forest management spectrum ranging from short rotation coppice to old-growth forests will be analyzed for its effects on the water, energy and carbon cycles. Climate response of forest will be quantified by means of albedo, evapotranspiration, greenhouse gas sources and sinks and their resulting climate feedback mechanisms. The anticipated new quantitative results will be used to lay the foundations for a portfolio of management strategies which will sustain wood production while minimizing climate change impacts. DOFOCO is interdisciplinary and ground breaking because it brings together state-of-the art data and models from applied life and Earth system sciences; it will deliver the first quantitative insights into how forest management strategies can be linked to climate change mitigation.
Summary
Forests, of which globally 70% are managed, play a particularly important role in the global carbon cycle. Recently, forest management became a top priority on the agenda of the political negotiations to mitigate climate change because forest plantations may remove atmospheric CO2 and if used for energy production, the wood is a substitute for fossil fuel. However, this political imperative is at present running well ahead of the science required to deliver it. Despite the key implications of forest management on: 1) the carbon-energy-water balance, and 2) production, recreation and environmental protection, there are no integrated studies of its effects on the Earth s climate. The overall goal of DOFOCO is to quantify and understand the role of forest management in mitigating climate change. Specifically, I want to challenge the current focus on the carbon cycle and replace it with a total climate impact approach. Hence, the whole forest management spectrum ranging from short rotation coppice to old-growth forests will be analyzed for its effects on the water, energy and carbon cycles. Climate response of forest will be quantified by means of albedo, evapotranspiration, greenhouse gas sources and sinks and their resulting climate feedback mechanisms. The anticipated new quantitative results will be used to lay the foundations for a portfolio of management strategies which will sustain wood production while minimizing climate change impacts. DOFOCO is interdisciplinary and ground breaking because it brings together state-of-the art data and models from applied life and Earth system sciences; it will deliver the first quantitative insights into how forest management strategies can be linked to climate change mitigation.
Max ERC Funding
1 296 125 €
Duration
Start date: 2010-02-01, End date: 2015-10-31
Project acronym DURABLERESISTANCE
Project Durable resistance against fungal plant pathogens
Researcher (PI) Beat Keller
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Advanced Grant (AdG), LS9, ERC-2009-AdG
Summary Plants and their pathogens are in a constant process of co-evolution. Consequently, many of the known defense genes of plants against fungal pathogens are rapidly loosing effectiveness under agricultural conditions. However, there are examples for durable resistance. It is one of the main research questions in plant biology to determine the genetic basis of such naturally occurring resistance and to understand the underlying biochemical and molecular cause for durability. This durability is characterized by the apparent inability of the pathogen to adapt to the resistance mechanism. The molecular understanding of durable resistance will contribute to future attempts to develop such resistance by design. We want to use two approaches towards understanding and developing durable resistance: the first one is based on the naturally occurring durable resistance gene Lr34 against rust and mildew diseases in wheat. This gene was recently isolated in our group and it encodes a putative ABC type of transporter protein, providing a possible link between non-host and durable resistance. Its function in resistance will be studied by genetic and biochemical approaches in the crop plant wheat, as there is no Lr34-type of resistance characterized in any other plant. However, there is a close Lr34-homolog in rice and its function will be investigated in this diploid system. The second approach will be based on natural diversity found in a specific resistance gene, conferring strong, but not durable resistance. This diversity will be used for a designed improvement of durability by developing new proteins or protein combinations to which the pathogen can not adapt. We will use the 15 naturally occurring alleles of the Pm3 powdery mildew resistance genes to identify the structural basis of specific interactions. Based on this characterization, we will develop intragenic or gene combination pyramiding strategies to obtain more broad-spectrum and more durable resistance.
Summary
Plants and their pathogens are in a constant process of co-evolution. Consequently, many of the known defense genes of plants against fungal pathogens are rapidly loosing effectiveness under agricultural conditions. However, there are examples for durable resistance. It is one of the main research questions in plant biology to determine the genetic basis of such naturally occurring resistance and to understand the underlying biochemical and molecular cause for durability. This durability is characterized by the apparent inability of the pathogen to adapt to the resistance mechanism. The molecular understanding of durable resistance will contribute to future attempts to develop such resistance by design. We want to use two approaches towards understanding and developing durable resistance: the first one is based on the naturally occurring durable resistance gene Lr34 against rust and mildew diseases in wheat. This gene was recently isolated in our group and it encodes a putative ABC type of transporter protein, providing a possible link between non-host and durable resistance. Its function in resistance will be studied by genetic and biochemical approaches in the crop plant wheat, as there is no Lr34-type of resistance characterized in any other plant. However, there is a close Lr34-homolog in rice and its function will be investigated in this diploid system. The second approach will be based on natural diversity found in a specific resistance gene, conferring strong, but not durable resistance. This diversity will be used for a designed improvement of durability by developing new proteins or protein combinations to which the pathogen can not adapt. We will use the 15 naturally occurring alleles of the Pm3 powdery mildew resistance genes to identify the structural basis of specific interactions. Based on this characterization, we will develop intragenic or gene combination pyramiding strategies to obtain more broad-spectrum and more durable resistance.
Max ERC Funding
2 100 000 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
