Project acronym ANAMMOX
Project Anaerobic ammonium oxidizing bacteria: unique prokayotes with exceptional properties
Researcher (PI) Michael Silvester Maria Jetten
Host Institution (HI) STICHTING KATHOLIEKE UNIVERSITEIT
Call Details Advanced Grant (AdG), LS8, ERC-2008-AdG
Summary For over a century it was believed that ammonium could only be oxidized by microbes in the presence of oxygen. The possibility of anaerobic ammonium oxidation (anammox) was considered impossible. However, about 10 years ago the microbes responsible for the anammox reaction were discovered in a wastewater plant. This was followed by the identification of the responsible bacteria. Recently, the widespread environmental occurrence of the anammox bacteria was demonstrated leading to the realization that anammox bacteria may play a major role in biological nitrogen cycling. The anammox bacteria are unique microbes with many unusual properties. These include the biological turn-over of hydrazine, a well known rocket fuel, the biological synthesis of ladderane lipids, and the presence of a prokaryotic organelle in the cytoplasma of anammox bacteria. The aim of this project is to obtain a fundamental understanding of the metabolism and ecological importance of the anammox bacteria. Such understanding contributes directly to our environment and economy because the anammox bacteria form a new opportunity for nitrogen removal from wastewater, cheaper, with lower carbon dioxide emissions than existing technology. Scientifically the results will contribute to the understanding how hydrazine and dinitrogen gas are made by the anammox bacteria. The research will show which gene products are responsible for the anammox reaction, and how their expression is regulated. Furthermore, the experiments proposed will show if the prokaryotic organelle in anammox bacteria is involved in energy generation. Together the environmental and metabolic data will help to understand why anammox bacteria are so successful in the biogeochemical nitrogen cycle and thus shape our planets atmosphere. The different research lines will employ state of the art microbial and molecular methods to unravel the exceptional properties of these highly unusual and important anammox bacteria.
Summary
For over a century it was believed that ammonium could only be oxidized by microbes in the presence of oxygen. The possibility of anaerobic ammonium oxidation (anammox) was considered impossible. However, about 10 years ago the microbes responsible for the anammox reaction were discovered in a wastewater plant. This was followed by the identification of the responsible bacteria. Recently, the widespread environmental occurrence of the anammox bacteria was demonstrated leading to the realization that anammox bacteria may play a major role in biological nitrogen cycling. The anammox bacteria are unique microbes with many unusual properties. These include the biological turn-over of hydrazine, a well known rocket fuel, the biological synthesis of ladderane lipids, and the presence of a prokaryotic organelle in the cytoplasma of anammox bacteria. The aim of this project is to obtain a fundamental understanding of the metabolism and ecological importance of the anammox bacteria. Such understanding contributes directly to our environment and economy because the anammox bacteria form a new opportunity for nitrogen removal from wastewater, cheaper, with lower carbon dioxide emissions than existing technology. Scientifically the results will contribute to the understanding how hydrazine and dinitrogen gas are made by the anammox bacteria. The research will show which gene products are responsible for the anammox reaction, and how their expression is regulated. Furthermore, the experiments proposed will show if the prokaryotic organelle in anammox bacteria is involved in energy generation. Together the environmental and metabolic data will help to understand why anammox bacteria are so successful in the biogeochemical nitrogen cycle and thus shape our planets atmosphere. The different research lines will employ state of the art microbial and molecular methods to unravel the exceptional properties of these highly unusual and important anammox bacteria.
Max ERC Funding
2 500 000 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym ANGIOMIRS
Project microRNAs in vascular homeostasis
Researcher (PI) Stefanie Dimmeler
Host Institution (HI) JOHANN WOLFGANG GOETHE-UNIVERSITATFRANKFURT AM MAIN
Call Details Advanced Grant (AdG), LS4, ERC-2008-AdG
Summary Despite improved therapy, cardiovascular diseases remain the most prevalent diseases in the European Union and the incidence is rising due to increased obesity and ageing. The fine-tuned regulation of vascular functions is essential not only for preventing atherosclerotic diseases, but also after tissue injury, where the coordinated growth and maturation of new blood vessels provides oxygen and nutrient supply. On the other hand, excessive vessel growth or the generation of immature, leaky vessels contributes to pathological angiogenesis. Thus, the regulation of the complex processes governing vessel growth and maturation has broad impacts for several diseases ranging from tumor angiogenesis, diabetic retinopathy, to ischemic cardiovascular diseases. MicroRNAs (miRs) are small noncoding RNAs, which play a crucial role in embryonic development and tissue homeostasis. However, only limited information is available regarding the role of miRs in the vasculature. MiRs regulate gene expression by binding to the target mRNA leading either to degradation or to translational repression. Because miRs control patterns of target genes, miRs represent an attractive and promising therapeutic target to interfere with complex processes such as neovascularization and repair of ischemic tissues. Therefore, the present application aims to identify miRs in the vasculature, which regulate vessel growth and vessel remodelling and may, thus, serve as therapeutic targets in ischemic diseases. Since ageing critically impairs endothelial function, neovascularization and vascular repair, we will specifically identify miRs, which are dysregulated during ageing in endothelial cells and pro-angiogenic progenitor cells, in order to develop novel strategies to rescue age-induced impairment of neovascularization. Beyond the specific scope of the present application, the principle findings may have impact for other diseases, where deregulated vessel growth causes or accelerates disease states.
Summary
Despite improved therapy, cardiovascular diseases remain the most prevalent diseases in the European Union and the incidence is rising due to increased obesity and ageing. The fine-tuned regulation of vascular functions is essential not only for preventing atherosclerotic diseases, but also after tissue injury, where the coordinated growth and maturation of new blood vessels provides oxygen and nutrient supply. On the other hand, excessive vessel growth or the generation of immature, leaky vessels contributes to pathological angiogenesis. Thus, the regulation of the complex processes governing vessel growth and maturation has broad impacts for several diseases ranging from tumor angiogenesis, diabetic retinopathy, to ischemic cardiovascular diseases. MicroRNAs (miRs) are small noncoding RNAs, which play a crucial role in embryonic development and tissue homeostasis. However, only limited information is available regarding the role of miRs in the vasculature. MiRs regulate gene expression by binding to the target mRNA leading either to degradation or to translational repression. Because miRs control patterns of target genes, miRs represent an attractive and promising therapeutic target to interfere with complex processes such as neovascularization and repair of ischemic tissues. Therefore, the present application aims to identify miRs in the vasculature, which regulate vessel growth and vessel remodelling and may, thus, serve as therapeutic targets in ischemic diseases. Since ageing critically impairs endothelial function, neovascularization and vascular repair, we will specifically identify miRs, which are dysregulated during ageing in endothelial cells and pro-angiogenic progenitor cells, in order to develop novel strategies to rescue age-induced impairment of neovascularization. Beyond the specific scope of the present application, the principle findings may have impact for other diseases, where deregulated vessel growth causes or accelerates disease states.
Max ERC Funding
2 375 394 €
Duration
Start date: 2009-03-01, End date: 2014-02-28
Project acronym ANTEGEFI
Project Analytic Techniques for Geometric and Functional Inequalities
Researcher (PI) Nicola Fusco
Host Institution (HI) UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II
Call Details Advanced Grant (AdG), PE1, ERC-2008-AdG
Summary Isoperimetric and Sobolev inequalities are the best known examples of geometric-functional inequalities. In recent years the PI and collaborators have obtained new and sharp quantitative versions of these and other important related inequalities. These results have been obtained by the combined use of classical symmetrization methods, new tools coming from mass transportation theory, deep geometric measure tools and ad hoc symmetrizations. The objective of this project is to further develop thes techniques in order to get: sharp quantitative versions of Faber-Krahn inequality, Gaussian isoperimetric inequality, Brunn-Minkowski inequality, Poincaré and Sobolev logarithm inequalities; sharp decay rates for the quantitative Sobolev inequalities and Polya-Szegö inequality.
Summary
Isoperimetric and Sobolev inequalities are the best known examples of geometric-functional inequalities. In recent years the PI and collaborators have obtained new and sharp quantitative versions of these and other important related inequalities. These results have been obtained by the combined use of classical symmetrization methods, new tools coming from mass transportation theory, deep geometric measure tools and ad hoc symmetrizations. The objective of this project is to further develop thes techniques in order to get: sharp quantitative versions of Faber-Krahn inequality, Gaussian isoperimetric inequality, Brunn-Minkowski inequality, Poincaré and Sobolev logarithm inequalities; sharp decay rates for the quantitative Sobolev inequalities and Polya-Szegö inequality.
Max ERC Funding
600 000 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym AP-1-FUN
Project AP-1 (Fos/Jun) Functions in Physiology and Disease
Researcher (PI) Erwin F. Wagner
Host Institution (HI) FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III
Call Details Advanced Grant (AdG), LS4, ERC-2008-AdG
Summary Our research interests lie in breaking new ground in studying mechanism-based functions of AP-1 (Fos/Jun) in vivo with the aim of obtaining a more global perspective on AP-1 in human physiology and disease/cancer. The unresolved issues regarding the AP-1 subunit composition will be tackled biochemically and genetically in various cell types including bone, liver and skin, the primary organs affected by altered AP-1 activity. I plan to utilize the knowledge gained on AP-1 functions in the mouse and transfer it to human disease. The opportunities here lie in exploiting the knowledge of AP-1 target genes and utilizing this information to interfere with pathways involved in normal physiology and disease/cancer. The past investigations revealed that the functions of AP-1 are an essential node at the crossroads between life and death in different cellular systems. I plan to further exploit our findings and concentrate on utilising better mouse models to define these connections. The emphasis will be on identifying molecular signatures and potential treatments in models for cancer, inflammatory and fibrotic diseases. Exploring genetically modified stem cell-based therapies in murine and human cells is an ongoing challenge I would like to meet in the forthcoming years at the CNIO. In addition, the mouse models will be used for mechanism-driven therapeutic strategies and these studies will be undertaken in collaboration with the Experimental Therapeutics Division and the service units such as the tumor bank. The project proposal is divided into 6 Goals (see also Figure 1): Some are a logical continuation based on previous work with completely new aspects (Goal 1-2), some focussing on in depth molecular analyses of disease models with innovative and unconventional concepts, such as for inflammation and cancer, psoriasis and fibrosis (Goal 3-5). A final section is devoted to mouse and human ES cells and their impact for regenerative medicine in bone diseases and cancer.
Summary
Our research interests lie in breaking new ground in studying mechanism-based functions of AP-1 (Fos/Jun) in vivo with the aim of obtaining a more global perspective on AP-1 in human physiology and disease/cancer. The unresolved issues regarding the AP-1 subunit composition will be tackled biochemically and genetically in various cell types including bone, liver and skin, the primary organs affected by altered AP-1 activity. I plan to utilize the knowledge gained on AP-1 functions in the mouse and transfer it to human disease. The opportunities here lie in exploiting the knowledge of AP-1 target genes and utilizing this information to interfere with pathways involved in normal physiology and disease/cancer. The past investigations revealed that the functions of AP-1 are an essential node at the crossroads between life and death in different cellular systems. I plan to further exploit our findings and concentrate on utilising better mouse models to define these connections. The emphasis will be on identifying molecular signatures and potential treatments in models for cancer, inflammatory and fibrotic diseases. Exploring genetically modified stem cell-based therapies in murine and human cells is an ongoing challenge I would like to meet in the forthcoming years at the CNIO. In addition, the mouse models will be used for mechanism-driven therapeutic strategies and these studies will be undertaken in collaboration with the Experimental Therapeutics Division and the service units such as the tumor bank. The project proposal is divided into 6 Goals (see also Figure 1): Some are a logical continuation based on previous work with completely new aspects (Goal 1-2), some focussing on in depth molecular analyses of disease models with innovative and unconventional concepts, such as for inflammation and cancer, psoriasis and fibrosis (Goal 3-5). A final section is devoted to mouse and human ES cells and their impact for regenerative medicine in bone diseases and cancer.
Max ERC Funding
2 500 000 €
Duration
Start date: 2009-11-01, End date: 2015-10-31
Project acronym APPROXNP
Project Approximation of NP-hard optimization problems
Researcher (PI) Johan Håstad
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Advanced Grant (AdG), PE6, ERC-2008-AdG
Summary The proposed project aims to create a center of excellence that aims at understanding the approximability of NP-hard optimization problems. In particular, for central problems like vertex cover, coloring of graphs, and various constraint satisfaction problems we want to study upper and lower bounds on how well they can be approximated in polynomial time. Many existing strong results are based on what is known as the Unique Games Conjecture (UGC) and a significant part of the project will be devoted to studying this conjecture. We expect that a major step needed to be taken in this process is to further develop the understanding of Boolean functions on the Boolean hypercube. We anticipate that the tools needed for this will come in the form of harmonic analysis which in its turn will rely on the corresponding results in the analysis of functions over the domain of real numbers.
Summary
The proposed project aims to create a center of excellence that aims at understanding the approximability of NP-hard optimization problems. In particular, for central problems like vertex cover, coloring of graphs, and various constraint satisfaction problems we want to study upper and lower bounds on how well they can be approximated in polynomial time. Many existing strong results are based on what is known as the Unique Games Conjecture (UGC) and a significant part of the project will be devoted to studying this conjecture. We expect that a major step needed to be taken in this process is to further develop the understanding of Boolean functions on the Boolean hypercube. We anticipate that the tools needed for this will come in the form of harmonic analysis which in its turn will rely on the corresponding results in the analysis of functions over the domain of real numbers.
Max ERC Funding
2 376 000 €
Duration
Start date: 2009-01-01, End date: 2014-12-31
Project acronym ASTRODYN
Project Astrophysical Dynamos
Researcher (PI) Axel Brandenburg
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Advanced Grant (AdG), PE9, ERC-2008-AdG
Summary Magnetic fields in stars, planets, accretion discs, and galaxies are believed to be the result of a dynamo process converting kinetic energy into magnetic energy. This work focuses on the solar dynamo, but dynamos in other astrophysical systems will also be addressed. In particular, direct high-resolution three-dimensional simulations are used to understand particular aspects of the solar dynamo and ultimately to simulate the solar dynamo as a whole. Phenomenological approaches will be avoided in favor of obtaining rigorous results. A major problem is catastrophic quenching, i.e. the decline of dynamo effects in inverse proportion to the magnetic Reynolds number, which is huge. Tremendous advances have been made in the last few years since the cause of catastrophic quenching in dynamos has been understood in terms of magnetic helicity evolution. The numerical tools are now in place to allow for magnetic helicity fluxes via coronal mass ejections, thus alleviating catastrophic quenching. This work employs simulations in spherical shells, augmented by Cartesian simulations in special cases. The roles of the near-surface shear layer, the tachocline, as well as pumping in the bulk of the convection zone are to be clarified. The Pencil Code will be used for most applications. The code is third order in time and sixth order in space and is used for solving the hydromagnetic equations. It is a public domain code developed by roughly 20 scientists world wide and maintained under an a central versioning system at Nordita. Automatic nightly tests of currently 30 applications ensure the integrity of the code. It is used for a wide range of applications and may include the effects of radiation, self-gravity, dust, chemistry, variable ionization, cosmic rays, in addition to those of magnetohydrodynamics. The code with its infrastructure offers a good opportunity for individuals within a broad group of people to develop new tools that may automatically be useful to others.
Summary
Magnetic fields in stars, planets, accretion discs, and galaxies are believed to be the result of a dynamo process converting kinetic energy into magnetic energy. This work focuses on the solar dynamo, but dynamos in other astrophysical systems will also be addressed. In particular, direct high-resolution three-dimensional simulations are used to understand particular aspects of the solar dynamo and ultimately to simulate the solar dynamo as a whole. Phenomenological approaches will be avoided in favor of obtaining rigorous results. A major problem is catastrophic quenching, i.e. the decline of dynamo effects in inverse proportion to the magnetic Reynolds number, which is huge. Tremendous advances have been made in the last few years since the cause of catastrophic quenching in dynamos has been understood in terms of magnetic helicity evolution. The numerical tools are now in place to allow for magnetic helicity fluxes via coronal mass ejections, thus alleviating catastrophic quenching. This work employs simulations in spherical shells, augmented by Cartesian simulations in special cases. The roles of the near-surface shear layer, the tachocline, as well as pumping in the bulk of the convection zone are to be clarified. The Pencil Code will be used for most applications. The code is third order in time and sixth order in space and is used for solving the hydromagnetic equations. It is a public domain code developed by roughly 20 scientists world wide and maintained under an a central versioning system at Nordita. Automatic nightly tests of currently 30 applications ensure the integrity of the code. It is used for a wide range of applications and may include the effects of radiation, self-gravity, dust, chemistry, variable ionization, cosmic rays, in addition to those of magnetohydrodynamics. The code with its infrastructure offers a good opportunity for individuals within a broad group of people to develop new tools that may automatically be useful to others.
Max ERC Funding
2 220 000 €
Duration
Start date: 2009-02-01, End date: 2014-01-31
Project acronym ATMNUCLE
Project Atmospheric nucleation: from molecular to global scale
Researcher (PI) Markku Tapio Kulmala
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Advanced Grant (AdG), PE10, ERC-2008-AdG
Summary Atmospheric aerosol particles and trace gases affect the quality of our life in many ways (e.g. health effects, changes in climate and hydrological cycle). Trace gases and atmospheric aerosols are tightly connected via physical, chemical, meteorological and biological processes occurring in the atmosphere and at the atmosphere-biosphere interface. One important phenomenon is atmospheric aerosol formation, which involves the production of nanometer-size particles by nucleation and their growth to detectable sizes. The main scientific objectives of this project are 1) to quantify the mechanisms responsible for atmospheric new particle formation and 2) to find out how important this process is for the behaviour of the global aerosol system and, ultimately, for the whole climate system. Our scientific plan is designed as a research chain that aims to advance our understanding of climate and air quality through a series of connected activities. We start from molecular simulations and laboratory measurements to understand nucleation and aerosol thermodynamic processes. We measure nanoparticles and atmospheric clusters at 15-20 sites all around the world using state of the art instrumentation and study feedbacks and interactions between climate and biosphere. With these atmospheric boundary layer studies we form a link to regional-scale processes and further to global-scale phenomena. In order to be able to simulate global climate and air quality, the most recent progress on this chain of processes must be compiled, integrated and implemented in Climate Change and Air Quality numerical models via novel parameterizations.
Summary
Atmospheric aerosol particles and trace gases affect the quality of our life in many ways (e.g. health effects, changes in climate and hydrological cycle). Trace gases and atmospheric aerosols are tightly connected via physical, chemical, meteorological and biological processes occurring in the atmosphere and at the atmosphere-biosphere interface. One important phenomenon is atmospheric aerosol formation, which involves the production of nanometer-size particles by nucleation and their growth to detectable sizes. The main scientific objectives of this project are 1) to quantify the mechanisms responsible for atmospheric new particle formation and 2) to find out how important this process is for the behaviour of the global aerosol system and, ultimately, for the whole climate system. Our scientific plan is designed as a research chain that aims to advance our understanding of climate and air quality through a series of connected activities. We start from molecular simulations and laboratory measurements to understand nucleation and aerosol thermodynamic processes. We measure nanoparticles and atmospheric clusters at 15-20 sites all around the world using state of the art instrumentation and study feedbacks and interactions between climate and biosphere. With these atmospheric boundary layer studies we form a link to regional-scale processes and further to global-scale phenomena. In order to be able to simulate global climate and air quality, the most recent progress on this chain of processes must be compiled, integrated and implemented in Climate Change and Air Quality numerical models via novel parameterizations.
Max ERC Funding
2 000 000 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym AUTOHEPARIN
Project Automated Synthesis of Heparin and Chondroitin Libraries for the Preparation of Diverse Carbohydrate Arrays
Researcher (PI) Peter Seeberger
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), PE5, ERC-2008-AdG
Summary While heparin, a glacosaminoglycan (GAG) has served as an anticoagulant for more than 60 years, the structure-activity relationship of heparin and chondroitin sulfate for specific interactions with proteins are still poorly understood. It has become evident that defined lengths and sequences or patterns are responsible for binding to a particular protein and modulating its biological activity. Determination of the structure-activity relationships of heparins and chondroitins creates an opportunity to modulate processes underlying viral entry, angiogenesis, kidney diseases and diseases of the central nervous system. The isolation of pure GAGs is extremely tedious and chemical synthesis is often the only means to access defined oligosaccharides. Currently available synthetic methods for the preparation of heparins and chondroitins are time consuming and lack generality. Therefore, it is still impossible to create large collections of GAG oligosaccharides for systematic studies of GAG-protein interactions. The overall goal of the project is the development of all aspects of automated GAG synthesis, the procurement of a large collection of heparin and chondroitin oligosaccharides of 2-10 sugars in length with a linker for ready attachment to microarray surfaces and other tools. These molecular tools will be employed to study the interaction of GAGs with growth factors, chemokines and other proteins. The specific aims include: 1) Synthesis of uronic acid and galactosamine building blocks; 2) Development of a new linker for automated GAG solid phase synthesis; 3) Construction of a new automated oligosaccharide synthesizer; 4) Development of methods for the automated assembly of heparin and chondroitin sulfate oligosaccharides; 5) Synthesis of a collection of defined heparin and chondroitin sulfate oligosaccharides; 6) Construction of synthetic GAG microarrays and SPR; 7) Preparation of GAG dendrimers and quantum dots.
Summary
While heparin, a glacosaminoglycan (GAG) has served as an anticoagulant for more than 60 years, the structure-activity relationship of heparin and chondroitin sulfate for specific interactions with proteins are still poorly understood. It has become evident that defined lengths and sequences or patterns are responsible for binding to a particular protein and modulating its biological activity. Determination of the structure-activity relationships of heparins and chondroitins creates an opportunity to modulate processes underlying viral entry, angiogenesis, kidney diseases and diseases of the central nervous system. The isolation of pure GAGs is extremely tedious and chemical synthesis is often the only means to access defined oligosaccharides. Currently available synthetic methods for the preparation of heparins and chondroitins are time consuming and lack generality. Therefore, it is still impossible to create large collections of GAG oligosaccharides for systematic studies of GAG-protein interactions. The overall goal of the project is the development of all aspects of automated GAG synthesis, the procurement of a large collection of heparin and chondroitin oligosaccharides of 2-10 sugars in length with a linker for ready attachment to microarray surfaces and other tools. These molecular tools will be employed to study the interaction of GAGs with growth factors, chemokines and other proteins. The specific aims include: 1) Synthesis of uronic acid and galactosamine building blocks; 2) Development of a new linker for automated GAG solid phase synthesis; 3) Construction of a new automated oligosaccharide synthesizer; 4) Development of methods for the automated assembly of heparin and chondroitin sulfate oligosaccharides; 5) Synthesis of a collection of defined heparin and chondroitin sulfate oligosaccharides; 6) Construction of synthetic GAG microarrays and SPR; 7) Preparation of GAG dendrimers and quantum dots.
Max ERC Funding
2 500 000 €
Duration
Start date: 2009-01-01, End date: 2014-12-31
Project acronym BCCI
Project Bidirectional cortical communication interface
Researcher (PI) Wolfgang Rosenstiel
Host Institution (HI) EBERHARD KARLS UNIVERSITAET TUEBINGEN
Call Details Advanced Grant (AdG), PE7, ERC-2008-AdG
Summary This project aims at establishing bidirectional communication via the cortical areas of the brain. In recent years there have been extensive research efforts for establishing an efferent pathway from the brain by means of cortical recordings to allow patients suffering from amyotrophic lateral sclerosis (ALS), stroke or high spinal cord lesions to interact with their environment (Birbaumer and Cohen, 2007; Wolpaw et al., 2002). As an extension this project will investigate the possibility of an afferent pathway to the brain by means of cortical stimulation, since it is ex-pected that stimulation might help to increase the information transfer rate for the efferent path-way. To achieve this there are two possible stimulation paradigms to be investigated. The first is based on the identification of optimal brain states for communication and the active maintenance of these states by stimulation. Inspired by classical conditioning, the second stimulation paradigm seeks to support and accelerate the rehabilitation process in stroke patients, as well as the learning process needed for the efferent communication pathway in ALS patients. By development of visual cortical prostheses (Schmidt et al., 1996) it became apparent that there are several fundamental problems related to cortical stimulation, which need to be solved before it is possible to evoke well-defined neural responses by stimulation - a prerequisite of the stimulation paradigms mentioned above. To overcome these problems it is envisaged to adapt stimulus parameters based on the current background brain activity by a feedback system in real time. Leveraging prior knowledge from microstimulation studies the feasibility of this approach will be evaluated by simultaneous stimulation and recording from ECoG grids and accompanied by the development of suitable algorithms.
Summary
This project aims at establishing bidirectional communication via the cortical areas of the brain. In recent years there have been extensive research efforts for establishing an efferent pathway from the brain by means of cortical recordings to allow patients suffering from amyotrophic lateral sclerosis (ALS), stroke or high spinal cord lesions to interact with their environment (Birbaumer and Cohen, 2007; Wolpaw et al., 2002). As an extension this project will investigate the possibility of an afferent pathway to the brain by means of cortical stimulation, since it is ex-pected that stimulation might help to increase the information transfer rate for the efferent path-way. To achieve this there are two possible stimulation paradigms to be investigated. The first is based on the identification of optimal brain states for communication and the active maintenance of these states by stimulation. Inspired by classical conditioning, the second stimulation paradigm seeks to support and accelerate the rehabilitation process in stroke patients, as well as the learning process needed for the efferent communication pathway in ALS patients. By development of visual cortical prostheses (Schmidt et al., 1996) it became apparent that there are several fundamental problems related to cortical stimulation, which need to be solved before it is possible to evoke well-defined neural responses by stimulation - a prerequisite of the stimulation paradigms mentioned above. To overcome these problems it is envisaged to adapt stimulus parameters based on the current background brain activity by a feedback system in real time. Leveraging prior knowledge from microstimulation studies the feasibility of this approach will be evaluated by simultaneous stimulation and recording from ECoG grids and accompanied by the development of suitable algorithms.
Max ERC Funding
1 169 400 €
Duration
Start date: 2009-02-01, End date: 2012-10-31
Project acronym BIOFORCE
Project Simultaneous multi-pathway engineering in crop plants through combinatorial genetic transformation: Creating nutritionally biofortified cereal grains for food security
Researcher (PI) Paul Christou
Host Institution (HI) UNIVERSIDAD DE LLEIDA
Call Details Advanced Grant (AdG), LS9, ERC-2008-AdG
Summary BIOFORCE has a highly ambitious applied objective: to create transgenic cereal plants that will provide a near-complete micronutrient complement (vitamins A, C, E, folate and essential minerals Ca, Fe, Se and Zn) for malnourished people in the developing world, as well as built-in resistance to insects and parasitic weeds. This in itself represents a striking advance over current efforts to address food insecurity using applied biotechnology in the developing world. We will also address fundamental mechanistic aspects of multi-gene/pathway engineering through transcriptome and metabolome profiling. Fundamental science and applied objectives will be achieved through the application of an exciting novel technology (combinatorial genetic transformation) developed and patented by my research group. This allows the simultaneous transfer of an unlimited number of transgenes into plants followed by library-based selection of plants with appropriate genotypes and phenotypes. All transgenes integrate into one locus ensuring expression stability over multiple generations. This proposal represents a new line of research in my laboratory, founded on incremental advances in the elucidation of transgene integration mechanisms in plants over the past two and a half decades. In addition to scientific issues, BIOFORCE address challenges such as intellectual property, regulatory and biosafety issues and crucially how the fruits of our work will be taken up through philanthropic initiatives in the developing world while creating exploitable opportunities elsewhere. BIOFORCE is comprehensive and it provides a complete package that stands to make an unprecedented contribution to food security in the developing world, while at the same time generating new knowledge to streamline and simplify multiplex gene transfer and the simultaneous modification of multiple complex plant metabolic pathways
Summary
BIOFORCE has a highly ambitious applied objective: to create transgenic cereal plants that will provide a near-complete micronutrient complement (vitamins A, C, E, folate and essential minerals Ca, Fe, Se and Zn) for malnourished people in the developing world, as well as built-in resistance to insects and parasitic weeds. This in itself represents a striking advance over current efforts to address food insecurity using applied biotechnology in the developing world. We will also address fundamental mechanistic aspects of multi-gene/pathway engineering through transcriptome and metabolome profiling. Fundamental science and applied objectives will be achieved through the application of an exciting novel technology (combinatorial genetic transformation) developed and patented by my research group. This allows the simultaneous transfer of an unlimited number of transgenes into plants followed by library-based selection of plants with appropriate genotypes and phenotypes. All transgenes integrate into one locus ensuring expression stability over multiple generations. This proposal represents a new line of research in my laboratory, founded on incremental advances in the elucidation of transgene integration mechanisms in plants over the past two and a half decades. In addition to scientific issues, BIOFORCE address challenges such as intellectual property, regulatory and biosafety issues and crucially how the fruits of our work will be taken up through philanthropic initiatives in the developing world while creating exploitable opportunities elsewhere. BIOFORCE is comprehensive and it provides a complete package that stands to make an unprecedented contribution to food security in the developing world, while at the same time generating new knowledge to streamline and simplify multiplex gene transfer and the simultaneous modification of multiple complex plant metabolic pathways
Max ERC Funding
2 290 046 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
