Project acronym IMMUNE/MEMORY AGING
Project Can immune system rejuvenation restore age-related memory loss?
Researcher (PI) Michal Eisenbach-Schwartz
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), LS5, ERC-2008-AdG
Summary With increased life expectancy, there has been a critical growth in the portion of the population that suffers from age-related cognitive decline and dementia. Attempts are therefore being made to find ways to slow brain-aging processes; successful therapies would have a significant impact on the quality of life of individuals, and decrease healthcare expenditures. Aging of the immune system has never been suggested as a factor in memory loss. My group formulated the concept of protective autoimmunity , suggesting a linkage between immunity and self-maintenance in the context of the brain in health and disease. Recently, we showed that T lymphocytes recognizing brain-self antigens have a pivotal role in maintaining hippocampal plasticity, as manifested by reduced neurogenesis and impaired cognitive abilities in T-cell deficient mice. Taken together, our novel observations that T cell immunity contributes to hippocampal plasticity, and the fact that T cell immunity decreases with progressive aging create the basis for the present proposal. We will focus on the following questions: (a) Which aspects of cognition are supported by the immune system- learning, memory or both; (b) whether aging of the immune system is sufficient to induce aging of the brain; (c) whether activation of the immune system is sufficient to reverse age-related cognitive decline; (d) the mechanism underlying the effect of peripheral immunity on brain cognition; and (e) potential therapeutic implications of our findings. Our preliminary results demonstrate that the immune system contributes to spatial memory, and that imposing an immune deficiency is sufficient to cause a reversible memory deficit. These findings give strong reason for optimism that memory loss in the elderly is preventable and perhaps reversible by immune-based therapies; we hope that, in the not too distant future, our studies will enable development of a vaccine to prevent CNS aging and cognitive loss in elderly.
Summary
With increased life expectancy, there has been a critical growth in the portion of the population that suffers from age-related cognitive decline and dementia. Attempts are therefore being made to find ways to slow brain-aging processes; successful therapies would have a significant impact on the quality of life of individuals, and decrease healthcare expenditures. Aging of the immune system has never been suggested as a factor in memory loss. My group formulated the concept of protective autoimmunity , suggesting a linkage between immunity and self-maintenance in the context of the brain in health and disease. Recently, we showed that T lymphocytes recognizing brain-self antigens have a pivotal role in maintaining hippocampal plasticity, as manifested by reduced neurogenesis and impaired cognitive abilities in T-cell deficient mice. Taken together, our novel observations that T cell immunity contributes to hippocampal plasticity, and the fact that T cell immunity decreases with progressive aging create the basis for the present proposal. We will focus on the following questions: (a) Which aspects of cognition are supported by the immune system- learning, memory or both; (b) whether aging of the immune system is sufficient to induce aging of the brain; (c) whether activation of the immune system is sufficient to reverse age-related cognitive decline; (d) the mechanism underlying the effect of peripheral immunity on brain cognition; and (e) potential therapeutic implications of our findings. Our preliminary results demonstrate that the immune system contributes to spatial memory, and that imposing an immune deficiency is sufficient to cause a reversible memory deficit. These findings give strong reason for optimism that memory loss in the elderly is preventable and perhaps reversible by immune-based therapies; we hope that, in the not too distant future, our studies will enable development of a vaccine to prevent CNS aging and cognitive loss in elderly.
Max ERC Funding
1 650 000 €
Duration
Start date: 2009-01-01, End date: 2012-12-31
Project acronym INNOSTOCH
Project INNOVATIONS IN STOCHASTIC ANALYSIS AND APPLICATIONS with emphasis on STOCHASTIC CONTROL AND INFORMATION
Researcher (PI) Bernt Karsten Øksendal
Host Institution (HI) UNIVERSITETET I OSLO
Call Details Advanced Grant (AdG), PE1, ERC-2008-AdG
Summary "For almost all kinds of dynamic systems modeling real processes in nature or society, most of the mathematical models we can formulate are - at best - inaccurate, and subject to random fluctuations and other types of ""noise"". Therefore it is important to be able to deal with such noisy models in a mathematically rigorous way. This rigorous theory is stochastic analysis. Theoretical progress in stochastic analysis will lead to new and improved applications in a wide range of fields.
The main purpose of this proposal is to establish a research environment which enhances the creation of new ideas and methods in the research of stochastic analysis and its applications. The emphasis is more on innovation, new models and challenges in the research frontiers, rather than small variations and minor improvements of already established theories and results. We will concentrate on applications in finance and biology, but the theoretical results may as well apply to several other areas.
Utilizing recent results and achievements by PI and a large group of distinguished coworkers, the natural extensions from the present knowledge is to concentrate on the mathematical theory of the interplay between stochastic analysis, stochastic control and information. More precisely, we have ambitions to make fundamental progress in the general theory of stochastic control of random systems and applications in finance and biology, and the explicit relation between the optimal performance and the amount of information available to the controller. Explicit examples of special interest include optimal control under partial or delayed information, and optimal control under inside or advanced information. A success of the present proposal will represent a substantial breakthrough, and in turn bring us a significant step forward in our attempts to understand various aspects of the world better, and it will help us to find optimal, sustainable ways to influence it."
Summary
"For almost all kinds of dynamic systems modeling real processes in nature or society, most of the mathematical models we can formulate are - at best - inaccurate, and subject to random fluctuations and other types of ""noise"". Therefore it is important to be able to deal with such noisy models in a mathematically rigorous way. This rigorous theory is stochastic analysis. Theoretical progress in stochastic analysis will lead to new and improved applications in a wide range of fields.
The main purpose of this proposal is to establish a research environment which enhances the creation of new ideas and methods in the research of stochastic analysis and its applications. The emphasis is more on innovation, new models and challenges in the research frontiers, rather than small variations and minor improvements of already established theories and results. We will concentrate on applications in finance and biology, but the theoretical results may as well apply to several other areas.
Utilizing recent results and achievements by PI and a large group of distinguished coworkers, the natural extensions from the present knowledge is to concentrate on the mathematical theory of the interplay between stochastic analysis, stochastic control and information. More precisely, we have ambitions to make fundamental progress in the general theory of stochastic control of random systems and applications in finance and biology, and the explicit relation between the optimal performance and the amount of information available to the controller. Explicit examples of special interest include optimal control under partial or delayed information, and optimal control under inside or advanced information. A success of the present proposal will represent a substantial breakthrough, and in turn bring us a significant step forward in our attempts to understand various aspects of the world better, and it will help us to find optimal, sustainable ways to influence it."
Max ERC Funding
1 864 800 €
Duration
Start date: 2009-09-01, End date: 2014-08-31
Project acronym INTERPLASTICITY
Project Long-term synaptic plasticity in interneurons: mechanisms and computational significance
Researcher (PI) Dimitri Michael Kullmann
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Advanced Grant (AdG), LS5, ERC-2008-AdG
Summary Memory encoding occurs by strengthening or weakening of synapses among principal neurons. However, excitatory synapses on some inhibitory neurons in the hippocampus also exhibit use-dependent long-term potentiation and depression (LTP and LTD), with important consequences for network homeostasis and information processing. This proposal addresses the following areas: 1. Although the rules determining which forms of plasticity occur at which synapses are emerging in the hippocampus, relatively little is known in other parts of the brain involved in cognition, movement initiation and emotion. We will use electrophysiology, optical imaging and mouse genetics to map out the expression of activity-dependent plasticity at excitatory synapses on inhibitory neurons in the cortex, striatum and amygdala, and relate these to the biophysical and pharmacological properties of the neurons and synapses involved. 2. Although one form of interneuron LTP resembles plasticity in pyramidal neurons, another form requires Ca2+-permeable AMPA receptors and metabotropic glutamate receptors for its induction, and shows features suggestive of pre-synaptic expression. A similar dichotomy exists in two forms of LTD, which depend on either NMDA or Ca2+-permeable AMPA and metabotropic glutamate receptors. We will test the involvement of candidate intracellular and trans-synaptic signalling cascades to understand the mechanisms triggered by distinct conjunction patterns of pre- and post-synaptic activity. 3. What is the computational significance of LTP and LTD in interneurons? The elemental computational roles of different GABAergic interneurons and their firing patterns during behaviourally relevant brain states are beginning to emerge. How synaptic strengthening and/or weakening interact with these network functions is however poorly understood. We will address this through a combination of hypothesis-driven experiments and numerical simulations.
Summary
Memory encoding occurs by strengthening or weakening of synapses among principal neurons. However, excitatory synapses on some inhibitory neurons in the hippocampus also exhibit use-dependent long-term potentiation and depression (LTP and LTD), with important consequences for network homeostasis and information processing. This proposal addresses the following areas: 1. Although the rules determining which forms of plasticity occur at which synapses are emerging in the hippocampus, relatively little is known in other parts of the brain involved in cognition, movement initiation and emotion. We will use electrophysiology, optical imaging and mouse genetics to map out the expression of activity-dependent plasticity at excitatory synapses on inhibitory neurons in the cortex, striatum and amygdala, and relate these to the biophysical and pharmacological properties of the neurons and synapses involved. 2. Although one form of interneuron LTP resembles plasticity in pyramidal neurons, another form requires Ca2+-permeable AMPA receptors and metabotropic glutamate receptors for its induction, and shows features suggestive of pre-synaptic expression. A similar dichotomy exists in two forms of LTD, which depend on either NMDA or Ca2+-permeable AMPA and metabotropic glutamate receptors. We will test the involvement of candidate intracellular and trans-synaptic signalling cascades to understand the mechanisms triggered by distinct conjunction patterns of pre- and post-synaptic activity. 3. What is the computational significance of LTP and LTD in interneurons? The elemental computational roles of different GABAergic interneurons and their firing patterns during behaviourally relevant brain states are beginning to emerge. How synaptic strengthening and/or weakening interact with these network functions is however poorly understood. We will address this through a combination of hypothesis-driven experiments and numerical simulations.
Max ERC Funding
2 500 000 €
Duration
Start date: 2009-10-01, End date: 2014-09-30
Project acronym M5CGS
Project From Mutations to Metastases: Multiscale Mathematical Modelling of Cancer Growth and Spread
Researcher (PI) Mark Andrew Joseph Chaplain
Host Institution (HI) UNIVERSITY OF DUNDEE
Call Details Advanced Grant (AdG), PE1, ERC-2008-AdG
Summary Cancer is one of the major causes of death in the world (particularly the developed world), with around 11 million people diagnosed and around 7 million people dying each year. The World Health Organisation predicts that current trends show around 9 million will die in 2015, with the number rising to 11.5 million in 2030. Cancer growth (viz. solid tumour growth) is a complicated phenomenon involving many inter-related processes across a wide range of spatial and temporal scales, and as such presents the mathematical modeller with a correspondingly complex set of problems to solve. This proposal will develop multi-scale mathematical models for the growth and spread of cancer and will focus on three main scales of interest: the sub-cellular, cellular and macroscopic. -- The sub-cellular scale refers to activities that take place within the cell or at the cell membrane, e.g. DNA synthesis, gene expression, cell cycle mechanisms, absorption of vital nutrients, activation or inactivation of receptors, transduction of chemical signals. -- The cellular scale refers to the main activities of the cells, e.g. statistical description of the progression and activation state of the cells, interactions among tumour cells and the other types of cells present in the body (such as endothelial cells, macrophages, lymphocytes), proliferative and destructive interactions, aggregation and disaggregation properties. -- The macroscopic scale refers to those phenomena which are typical of continuum systems, e.g. cell migration, diffusion and transport of nutrients and chemical factors, mechanical responses, interactions between different tissues, tissue remodelling. The proposal is multi-disciplinary in nature and aims to develop quantitative, predictive mathematical models of solid tumour growth which can ultimately be used in planning patient-specific treatment protocols such as chemotherapy, surgery and radiotherapy.
Summary
Cancer is one of the major causes of death in the world (particularly the developed world), with around 11 million people diagnosed and around 7 million people dying each year. The World Health Organisation predicts that current trends show around 9 million will die in 2015, with the number rising to 11.5 million in 2030. Cancer growth (viz. solid tumour growth) is a complicated phenomenon involving many inter-related processes across a wide range of spatial and temporal scales, and as such presents the mathematical modeller with a correspondingly complex set of problems to solve. This proposal will develop multi-scale mathematical models for the growth and spread of cancer and will focus on three main scales of interest: the sub-cellular, cellular and macroscopic. -- The sub-cellular scale refers to activities that take place within the cell or at the cell membrane, e.g. DNA synthesis, gene expression, cell cycle mechanisms, absorption of vital nutrients, activation or inactivation of receptors, transduction of chemical signals. -- The cellular scale refers to the main activities of the cells, e.g. statistical description of the progression and activation state of the cells, interactions among tumour cells and the other types of cells present in the body (such as endothelial cells, macrophages, lymphocytes), proliferative and destructive interactions, aggregation and disaggregation properties. -- The macroscopic scale refers to those phenomena which are typical of continuum systems, e.g. cell migration, diffusion and transport of nutrients and chemical factors, mechanical responses, interactions between different tissues, tissue remodelling. The proposal is multi-disciplinary in nature and aims to develop quantitative, predictive mathematical models of solid tumour growth which can ultimately be used in planning patient-specific treatment protocols such as chemotherapy, surgery and radiotherapy.
Max ERC Funding
1 680 974 €
Duration
Start date: 2009-09-01, End date: 2014-08-31
Project acronym MASSTEV
Project Mass hierarchy and particle physics at the TeV scale
Researcher (PI) Ignatios Antoniadis
Host Institution (HI) EUROPEAN ORGANIZATION FOR NUCLEAR RESEARCH
Call Details Advanced Grant (AdG), PE2, ERC-2008-AdG
Summary The research goal of this proposal is the investigation of the most fundamental aspects of particle physics models and gravity at high energies, and establishing the connection between these findings and experiments. The main fundamental questions that will be addressed are: What is the origin of mass for the mediators of the weak interactions and its connection with the masses of quarks and leptons? Why this mass is hierarchically different from the Planck scale which makes gravity so weak compared to the other three known fundamental interactions described by the current Standard Model of particle physics? Why this enormous mass hierarchy is quantum mechanically stable? What is the theory that describes physical laws at TeV energies which will be explored in the near future by the Large Hadron Collider at CERN? These questions are at the very frontier of knowledge of theoretical particle physics and phenomenology and their intersection with gravity and string theory. All members of the proposed research team have made breakthrough contributions in putting forward and developing new ideas that dominated such a research during the past 10 years. Although there is a certain overlap in the interests, each member brings a different unique expertise to the research, which will strongly resonate with the other members activity. Obviously, this project is strongly correlated with LHC physics confronting theoretical predictions with observations and using experimental data for building new theories and correcting existing models. In such an intense dynamical process, participation of doctoral students and postdoctoral researchers will be absolutely crucial and their active involvement is an essential component of the project. The main funding required by the project from the EU is for hiring of 14 person-years of PhD students and 14 person-years of postdocs.
Summary
The research goal of this proposal is the investigation of the most fundamental aspects of particle physics models and gravity at high energies, and establishing the connection between these findings and experiments. The main fundamental questions that will be addressed are: What is the origin of mass for the mediators of the weak interactions and its connection with the masses of quarks and leptons? Why this mass is hierarchically different from the Planck scale which makes gravity so weak compared to the other three known fundamental interactions described by the current Standard Model of particle physics? Why this enormous mass hierarchy is quantum mechanically stable? What is the theory that describes physical laws at TeV energies which will be explored in the near future by the Large Hadron Collider at CERN? These questions are at the very frontier of knowledge of theoretical particle physics and phenomenology and their intersection with gravity and string theory. All members of the proposed research team have made breakthrough contributions in putting forward and developing new ideas that dominated such a research during the past 10 years. Although there is a certain overlap in the interests, each member brings a different unique expertise to the research, which will strongly resonate with the other members activity. Obviously, this project is strongly correlated with LHC physics confronting theoretical predictions with observations and using experimental data for building new theories and correcting existing models. In such an intense dynamical process, participation of doctoral students and postdoctoral researchers will be absolutely crucial and their active involvement is an essential component of the project. The main funding required by the project from the EU is for hiring of 14 person-years of PhD students and 14 person-years of postdocs.
Max ERC Funding
1 999 992 €
Duration
Start date: 2008-12-01, End date: 2014-08-31
Project acronym MATHCARD
Project Mathematical Modelling and Simulation of the Cardiovascular System
Researcher (PI) Alfio Quarteroni
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Advanced Grant (AdG), PE1, ERC-2008-AdG
Summary This research project aims at the development, analysis and computer implementation of mathematical models of the cardiovascular system. Our goal is to describe and simulate the anatomic structure and the physiological response of the human cardiovascular system in healthy or diseased states. This demands to address many fundamental issues. Blood flow interacts both mechanically and chemically with the vessel walls and tissue, giving rise to complex fluid-structure interaction problems. The mathematical analysis of these problems is complicated and the related numerical analysis difficult. We propose to extend the recently achieved results on blood flow simulations by directing our analysis in several new directions. Our goal is to encompass aspects of metabolic regulation, micro-circulation, the electrical and mechanical activity of the heart, and their interactions. Modelling and optimisation of drugs delivery in clinical diseases will be addressed as well. This requires the understanding of transport, diffusion and reaction processes within the blood and organs of the body. The emphasis of this project will be put on mathematical modelling, numerical analysis, algorithm implementation, computational efficiency, validation and verification. Our purpose is to set up a mathematical simulation platform eventually leading to the improvement of vascular diseases diagnosis, setting up of surgical planning, and cure of inflammatory processes in the circulatory system. This platform might also help physicians to construct and evaluate combined anatomic/physiological models to predict the outcome of alternative treatment plans for individual patients.
Summary
This research project aims at the development, analysis and computer implementation of mathematical models of the cardiovascular system. Our goal is to describe and simulate the anatomic structure and the physiological response of the human cardiovascular system in healthy or diseased states. This demands to address many fundamental issues. Blood flow interacts both mechanically and chemically with the vessel walls and tissue, giving rise to complex fluid-structure interaction problems. The mathematical analysis of these problems is complicated and the related numerical analysis difficult. We propose to extend the recently achieved results on blood flow simulations by directing our analysis in several new directions. Our goal is to encompass aspects of metabolic regulation, micro-circulation, the electrical and mechanical activity of the heart, and their interactions. Modelling and optimisation of drugs delivery in clinical diseases will be addressed as well. This requires the understanding of transport, diffusion and reaction processes within the blood and organs of the body. The emphasis of this project will be put on mathematical modelling, numerical analysis, algorithm implementation, computational efficiency, validation and verification. Our purpose is to set up a mathematical simulation platform eventually leading to the improvement of vascular diseases diagnosis, setting up of surgical planning, and cure of inflammatory processes in the circulatory system. This platform might also help physicians to construct and evaluate combined anatomic/physiological models to predict the outcome of alternative treatment plans for individual patients.
Max ERC Funding
1 810 992 €
Duration
Start date: 2009-01-01, End date: 2014-06-30
Project acronym MITO BY-PASS
Project Molecular by-pass therapy for mitochondrial dysfunction
Researcher (PI) Howard Trevor Jacobs
Host Institution (HI) TAMPEREEN YLIOPISTO
Call Details Advanced Grant (AdG), LS4, ERC-2008-AdG
Summary Many eukaryotes, but not the higher metazoans such as vertebrates or arthropods, possess intrinsic by-pass systems that provide alternative routes for electron flow from NADH to oxygen. Whereas the standard mitochondrial OXPHOS system couples electron transport to proton pumping across the inner mitochondrial membrane, creating the proton gradient which is used to drive ATP synthesis and other energy-requiring processes, the by-pass enzymes are non-proton-pumping, and their activity is redox-regulated rather than subject to ATP requirements. My laboratory has engineered two of these by-pass enzymes, the single-subunit NADH dehydrogenase Ndi1p from yeast, and the alternative oxidase AOX from Ciona intestinalis, for expression in Drosophila and mammalian cells. Their expression is benign, and the enzymes appear to be almost inert, except under conditions of redox stress induced by OXPHOS toxins or mutations. The research set out in this proposal will explore the utility of these by-passes for alleviating metabolic stress in the whole organism and in specific tissues, arising from mitochondrial OXPHOS dysfunction. Specifically, I will test the ability of Ndi1p and AOX in Drosophila and in mammalian models to compensate for the toxicity of OXPHOS poisons, to complement disease-equivalent mutations impairing the assembly or function of the OXPHOS system, and to diminish the pathological excess production of reactive oxygen species seen in many neurodegenerative disorders associated with OXPHOS impairment, and under conditions of ischemia-reperfusion. The attenuation of endogenous mitochondrial ROS production by deployment of these by-pass enzymes also offers a novel route to testing the mitochondrial (oxyradical) theory of ageing.
Summary
Many eukaryotes, but not the higher metazoans such as vertebrates or arthropods, possess intrinsic by-pass systems that provide alternative routes for electron flow from NADH to oxygen. Whereas the standard mitochondrial OXPHOS system couples electron transport to proton pumping across the inner mitochondrial membrane, creating the proton gradient which is used to drive ATP synthesis and other energy-requiring processes, the by-pass enzymes are non-proton-pumping, and their activity is redox-regulated rather than subject to ATP requirements. My laboratory has engineered two of these by-pass enzymes, the single-subunit NADH dehydrogenase Ndi1p from yeast, and the alternative oxidase AOX from Ciona intestinalis, for expression in Drosophila and mammalian cells. Their expression is benign, and the enzymes appear to be almost inert, except under conditions of redox stress induced by OXPHOS toxins or mutations. The research set out in this proposal will explore the utility of these by-passes for alleviating metabolic stress in the whole organism and in specific tissues, arising from mitochondrial OXPHOS dysfunction. Specifically, I will test the ability of Ndi1p and AOX in Drosophila and in mammalian models to compensate for the toxicity of OXPHOS poisons, to complement disease-equivalent mutations impairing the assembly or function of the OXPHOS system, and to diminish the pathological excess production of reactive oxygen species seen in many neurodegenerative disorders associated with OXPHOS impairment, and under conditions of ischemia-reperfusion. The attenuation of endogenous mitochondrial ROS production by deployment of these by-pass enzymes also offers a novel route to testing the mitochondrial (oxyradical) theory of ageing.
Max ERC Funding
2 436 000 €
Duration
Start date: 2009-04-01, End date: 2015-03-31
Project acronym MM-PGT
Project Modern Methods for Perturbative Gauge Theories
Researcher (PI) David A. Kosower
Host Institution (HI) COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
Call Details Advanced Grant (AdG), PE2, ERC-2008-AdG
Summary Gauge theories are the basis of modern theories of high-energy physics. Perturbative calculations are crucial to developing our quantitative understanding of these theories, as well as seeking new and deeper structures in these theories. Precision higher-order calculations in the SU(3) component of the Standard Model, perturbative Quantum Chromodynamics (QCD), will be crucial to understanding data at the CERN-based Large Hadron Collider (LHC) and finding and measuring physics beyond the standard model. Precision calculations in the electroweak theory will also play a role in confronting later precision data with theoretical models. The related maximally (N=4) supersymmetric gauge theory has served both as an important theoretical laboratory for developing new calculational techniques, as well as a link to string theory via the AdS/CFT duality. It is also emerging as a fruitful meeting point for ideas and methods from three distinct areas of theoretical physics: perturbative gauge theories, integrable systems, and string theory. The Project covers three related areas of perturbative gauge theories: computation of one- and two-loop amplitudes in perturbative quantum chromodynamics; incorporation of these amplitudes and development of a fully-matched parton-shower formalism and numerical code; and higher-loop computations in the N=4 supersymmetric theory. It aims to develop a general-purpose numerical-analytic hybrid program for computing phenomenologically-relevant one- and two-loop amplitudes in perturbative QCD. It also aims to develop a new parton shower allowing complete matching to leading and next-to-leading order computations. It seeks to further develop on-shell computational methods, and apply them to the N=4 supersymmetric gauge theory, with the goal of connecting perturbative quantities to their strong-coupling counterparts computed using the dual string theory.
Summary
Gauge theories are the basis of modern theories of high-energy physics. Perturbative calculations are crucial to developing our quantitative understanding of these theories, as well as seeking new and deeper structures in these theories. Precision higher-order calculations in the SU(3) component of the Standard Model, perturbative Quantum Chromodynamics (QCD), will be crucial to understanding data at the CERN-based Large Hadron Collider (LHC) and finding and measuring physics beyond the standard model. Precision calculations in the electroweak theory will also play a role in confronting later precision data with theoretical models. The related maximally (N=4) supersymmetric gauge theory has served both as an important theoretical laboratory for developing new calculational techniques, as well as a link to string theory via the AdS/CFT duality. It is also emerging as a fruitful meeting point for ideas and methods from three distinct areas of theoretical physics: perturbative gauge theories, integrable systems, and string theory. The Project covers three related areas of perturbative gauge theories: computation of one- and two-loop amplitudes in perturbative quantum chromodynamics; incorporation of these amplitudes and development of a fully-matched parton-shower formalism and numerical code; and higher-loop computations in the N=4 supersymmetric theory. It aims to develop a general-purpose numerical-analytic hybrid program for computing phenomenologically-relevant one- and two-loop amplitudes in perturbative QCD. It also aims to develop a new parton shower allowing complete matching to leading and next-to-leading order computations. It seeks to further develop on-shell computational methods, and apply them to the N=4 supersymmetric gauge theory, with the goal of connecting perturbative quantities to their strong-coupling counterparts computed using the dual string theory.
Max ERC Funding
961 080 €
Duration
Start date: 2009-01-01, End date: 2014-12-31
Project acronym MOBILE
Project Modelling, Optimization and Control of Biomedical Systems
Researcher (PI) Efstratios Pistikopoulos
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Advanced Grant (AdG), PE7, ERC-2008-AdG
Summary The main aim of the proposed project is to develop models and model based control and optimization methods and tools for drug delivery systems, which would ensure: (i) Reliable and fast calculation of the optimal drug dosage without the need for an on-line computer while taking into account the specifics and constraints of the patient model (personalised health care) (ii) Flexibility to adapt to changing patient characteristics, (iii) Incorporation of the physician s performance criteria (iv) Safety of the patients (v) Reduced size effects by optimising the drug infusion rates The overall control and optimisation approach will rely on the novel multi-parametric model-based control technology developed by the PI over the past 15 years, which will be further extended and implemented in the context of the following biomedical systems (a) insulin delivery (b) control of anaesthesia and hemodynamic variables, (c) optimal chemotherapy design for anti-cancer (d) optimal control of the chemotherapy for HIV.
Summary
The main aim of the proposed project is to develop models and model based control and optimization methods and tools for drug delivery systems, which would ensure: (i) Reliable and fast calculation of the optimal drug dosage without the need for an on-line computer while taking into account the specifics and constraints of the patient model (personalised health care) (ii) Flexibility to adapt to changing patient characteristics, (iii) Incorporation of the physician s performance criteria (iv) Safety of the patients (v) Reduced size effects by optimising the drug infusion rates The overall control and optimisation approach will rely on the novel multi-parametric model-based control technology developed by the PI over the past 15 years, which will be further extended and implemented in the context of the following biomedical systems (a) insulin delivery (b) control of anaesthesia and hemodynamic variables, (c) optimal chemotherapy design for anti-cancer (d) optimal control of the chemotherapy for HIV.
Max ERC Funding
1 782 925 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym MORIAE
Project HUMAN AND MOUSE MODELS OF RHINOVIRUS INDUCED ACUTE ASTHMA EXACERBATIONS
Researcher (PI) Sebastian Lennox Johnston
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Advanced Grant (AdG), LS4, ERC-2008-AdG
Summary Asthma is the most common chronic respiratory disease and in many countries prevalence continues to rise. The major cause of asthma morbidity, mortality and health care costs are acute exacerbations, with rhinovirus infection the major cause. The aim of this application is to identify novel targets for the development of new more effective therapies for treatment and prevention of virus-induced asthma exacerbations, a disease area where there is a major unmet current clinical need. This proposal combines two unique state of the art novel models of acute exacerbations of asthma. First, a human model will be used to identify dysregulated genes/proteins and determine relationships with disease outcomes in vivo. This study will compare lower airway responses between asthmatic and control subjects undergoing rhinovirus experimental infection. This will have the dual advantage of investigating mechanisms in the most natural model possible, as well as developing a better model for testing novel therapeutic approaches. The second utilizes a unique new mouse model of rhinovirus infection in which causal relationships with disease outcomes can be investigated in vivo. This will be performed using gene-knockout mice, blocking antibodies, siRNA, pharmacologic inhibition and/or over-expression in genes in a novel mouse model of rhinovirus exacerbation. Any genes/proteins shown to be dysregulated and related to disease outcomes in the human model, AND causally related to disease outcomes in the mouse in vivo model will be very strong candidates for immediate translation of approaches to correct the dysregulation in proof of concept pivotal human intervention studies. The development of a new low dose challenge human model proposed will also provide a new and optimal model of naturally occurring exacerbations, in which such proof of concept pivotal human intervention studies can be carried out.
Summary
Asthma is the most common chronic respiratory disease and in many countries prevalence continues to rise. The major cause of asthma morbidity, mortality and health care costs are acute exacerbations, with rhinovirus infection the major cause. The aim of this application is to identify novel targets for the development of new more effective therapies for treatment and prevention of virus-induced asthma exacerbations, a disease area where there is a major unmet current clinical need. This proposal combines two unique state of the art novel models of acute exacerbations of asthma. First, a human model will be used to identify dysregulated genes/proteins and determine relationships with disease outcomes in vivo. This study will compare lower airway responses between asthmatic and control subjects undergoing rhinovirus experimental infection. This will have the dual advantage of investigating mechanisms in the most natural model possible, as well as developing a better model for testing novel therapeutic approaches. The second utilizes a unique new mouse model of rhinovirus infection in which causal relationships with disease outcomes can be investigated in vivo. This will be performed using gene-knockout mice, blocking antibodies, siRNA, pharmacologic inhibition and/or over-expression in genes in a novel mouse model of rhinovirus exacerbation. Any genes/proteins shown to be dysregulated and related to disease outcomes in the human model, AND causally related to disease outcomes in the mouse in vivo model will be very strong candidates for immediate translation of approaches to correct the dysregulation in proof of concept pivotal human intervention studies. The development of a new low dose challenge human model proposed will also provide a new and optimal model of naturally occurring exacerbations, in which such proof of concept pivotal human intervention studies can be carried out.
Max ERC Funding
2 497 761 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
