Project acronym BODY-OWNERSHIP
Project Neural mechanisms of body ownership and the projection of ownership onto artificial bodies
Researcher (PI) H. Henrik Ehrsson
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS4, ERC-2007-StG
Summary How do we recognize that our limbs are part of our own body, and why do we feel that one’s self is located inside the body? These fundamental questions have been discussed in theology, philosophy and psychology for millennia. The aim of my ground-breaking research programme is to identify the neuronal mechanisms that produce the sense of ownership of the body, and the processes responsible for the feeling that the self is located inside the physical body. To solve these questions I will adopt an inter-disciplinary approach using state-of-the-art methods from the fields of imaging neuroscience, experimental psychology, computer science and robotics. My first hypothesis is that the mechanism for body ownership is the integration of information from different sensory modalities (vision, touch and muscle sense) in multi-sensory brain areas (ventral premotor and intraparietal cortex). My second hypothesis is that the sense of where you are located in the environment is mediated by allocentric spatial representations in medial temporal lobes. To test this, I will use perceptual illusions and virtual-reality techniques that allow me to manipulate body ownership and the perceived location of the self, in conjunction with non-invasive recordings of brain activity in healthy humans. Functional magnetic resonance imaging and electroencephalography will be used to identify the neuronal correlates of ownership and ‘in-body experiences’, while transcranial magnetic stimulation will be used to examine the causal relationship between neural activity and ownership. It is no overstatement to say that my pioneering work could define a new sub-field in cognitive neuroscience dealing with how the brain represents the self. These basic scientific discoveries will be used in new frontier applications. For example, the development of a prosthetic limb that feels just like a real limb, and a method of controlling humanoid robots by the illusion of ‘becoming the robot’.
Summary
How do we recognize that our limbs are part of our own body, and why do we feel that one’s self is located inside the body? These fundamental questions have been discussed in theology, philosophy and psychology for millennia. The aim of my ground-breaking research programme is to identify the neuronal mechanisms that produce the sense of ownership of the body, and the processes responsible for the feeling that the self is located inside the physical body. To solve these questions I will adopt an inter-disciplinary approach using state-of-the-art methods from the fields of imaging neuroscience, experimental psychology, computer science and robotics. My first hypothesis is that the mechanism for body ownership is the integration of information from different sensory modalities (vision, touch and muscle sense) in multi-sensory brain areas (ventral premotor and intraparietal cortex). My second hypothesis is that the sense of where you are located in the environment is mediated by allocentric spatial representations in medial temporal lobes. To test this, I will use perceptual illusions and virtual-reality techniques that allow me to manipulate body ownership and the perceived location of the self, in conjunction with non-invasive recordings of brain activity in healthy humans. Functional magnetic resonance imaging and electroencephalography will be used to identify the neuronal correlates of ownership and ‘in-body experiences’, while transcranial magnetic stimulation will be used to examine the causal relationship between neural activity and ownership. It is no overstatement to say that my pioneering work could define a new sub-field in cognitive neuroscience dealing with how the brain represents the self. These basic scientific discoveries will be used in new frontier applications. For example, the development of a prosthetic limb that feels just like a real limb, and a method of controlling humanoid robots by the illusion of ‘becoming the robot’.
Max ERC Funding
909 850 €
Duration
Start date: 2008-12-01, End date: 2013-11-30
Project acronym BUCOPHSYS
Project Bottom-up hybrid control and planning synthesis with application to multi-robot multi-human coordination
Researcher (PI) DIMOS Dimarogonas
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Starting Grant (StG), PE7, ERC-2014-STG
Summary Current control applications necessitate the treatment of systems with multiple interconnected components, rather than the traditional single component paradigm that has been studied extensively. The individual subsystems may need to fulfil different and possibly conflicting specifications in a real-time manner. At the same time, they may need to fulfill coupled constraints that are defined as relations between their states. Towards this end, the need for methods for decentralized control at the continuous level and planning at the task level becomes apparent. We aim here towards unification of these two complementary approaches. Existing solutions rely on a top down centralized approach. We instead consider here a decentralized, bottom-up solution to the problem. The approach relies on three layers of interaction. In the first layer, agents aim at coordinating in order to fulfil their coupled constraints with limited communication exchange of their state information and design of appropriate feedback controllers; in the second layer, agents coordinate in order to mutually satisfy their discrete tasks through exchange of the corresponding plans in the form of automata; in the third and most challenging layer, the communication exchange for coordination now includes both continuous state and discrete plan/abstraction information. The results will be demonstrated in a scenario involving multiple (possibly human) users and multiple robots.
The unification will yield a completely decentralized system, in which the bottom up approach to define tasks, the consideration of coupled constraints and their combination towards distributed hybrid control and planning in a coordinated fashion require for
new ways of thinking and approaches to analysis and constitute the proposal a beyond the SoA and groundbreaking approach to the fields of control and computer science.
Summary
Current control applications necessitate the treatment of systems with multiple interconnected components, rather than the traditional single component paradigm that has been studied extensively. The individual subsystems may need to fulfil different and possibly conflicting specifications in a real-time manner. At the same time, they may need to fulfill coupled constraints that are defined as relations between their states. Towards this end, the need for methods for decentralized control at the continuous level and planning at the task level becomes apparent. We aim here towards unification of these two complementary approaches. Existing solutions rely on a top down centralized approach. We instead consider here a decentralized, bottom-up solution to the problem. The approach relies on three layers of interaction. In the first layer, agents aim at coordinating in order to fulfil their coupled constraints with limited communication exchange of their state information and design of appropriate feedback controllers; in the second layer, agents coordinate in order to mutually satisfy their discrete tasks through exchange of the corresponding plans in the form of automata; in the third and most challenging layer, the communication exchange for coordination now includes both continuous state and discrete plan/abstraction information. The results will be demonstrated in a scenario involving multiple (possibly human) users and multiple robots.
The unification will yield a completely decentralized system, in which the bottom up approach to define tasks, the consideration of coupled constraints and their combination towards distributed hybrid control and planning in a coordinated fashion require for
new ways of thinking and approaches to analysis and constitute the proposal a beyond the SoA and groundbreaking approach to the fields of control and computer science.
Max ERC Funding
1 498 729 €
Duration
Start date: 2015-03-01, End date: 2020-02-29
Project acronym CAAXPROCESSINGHUMDIS
Project CAAX Protein Processing in Human DIsease: From Cancer to Progeria
Researcher (PI) Martin Olof Bergö
Host Institution (HI) GOETEBORGS UNIVERSITET
Call Details Starting Grant (StG), LS6, ERC-2007-StG
Summary My objective is to understand the physiologic and medical importance of the posttranslational processing of CAAX proteins (e.g., K-RAS and prelamin A) and to define the suitability of the CAAX protein processing enzymes as therapeutic targets for the treatment of cancer and progeria. CAAX proteins undergo three posttranslational processing steps at a carboxyl-terminal CAAX motif. These processing steps, which are mediated by four different enzymes (FTase, GGTase-I, RCE1, and ICMT), increase the hydrophobicity of the carboxyl terminus of the protein and thereby facilitate interactions with membrane surfaces. Somatic mutations in K-RAS deregulate cell growth and are etiologically involved in the pathogenesis of many forms of cancer. A mutation in prelamin A causes Hutchinson-Gilford progeria syndrome—a pediatric progeroid syndrome associated with misshaped cell nuclei and a host of aging-like disease phenotypes. One strategy to render the mutant K-RAS and prelamin A less harmful is to interfere with their ability to bind to membrane surfaces (e.g., the plasma membrane and the nuclear envelope). This could be accomplished by inhibiting the enzymes that modify the CAAX motif. My Specific Aims are: (1) To define the suitability of the CAAX processing enzymes as therapeutic targets in the treatment of K-RAS-induced lung cancer and leukemia; and (2) To test the hypothesis that inactivation of FTase or ICMT will ameliorate disease phenotypes of progeria. I have developed genetic strategies to produce lung cancer or leukemia in mice by activating an oncogenic K-RAS and simultaneously inactivating different CAAX processing enzymes. I will also inactivate several CAAX processing enzymes in mice with progeria—both before the emergence of phenotypes and after the development of advanced disease phenotypes. These experiments should reveal whether the absence of the different CAAX processing enzymes affects the onset, progression, or regression of cancer and progeria.
Summary
My objective is to understand the physiologic and medical importance of the posttranslational processing of CAAX proteins (e.g., K-RAS and prelamin A) and to define the suitability of the CAAX protein processing enzymes as therapeutic targets for the treatment of cancer and progeria. CAAX proteins undergo three posttranslational processing steps at a carboxyl-terminal CAAX motif. These processing steps, which are mediated by four different enzymes (FTase, GGTase-I, RCE1, and ICMT), increase the hydrophobicity of the carboxyl terminus of the protein and thereby facilitate interactions with membrane surfaces. Somatic mutations in K-RAS deregulate cell growth and are etiologically involved in the pathogenesis of many forms of cancer. A mutation in prelamin A causes Hutchinson-Gilford progeria syndrome—a pediatric progeroid syndrome associated with misshaped cell nuclei and a host of aging-like disease phenotypes. One strategy to render the mutant K-RAS and prelamin A less harmful is to interfere with their ability to bind to membrane surfaces (e.g., the plasma membrane and the nuclear envelope). This could be accomplished by inhibiting the enzymes that modify the CAAX motif. My Specific Aims are: (1) To define the suitability of the CAAX processing enzymes as therapeutic targets in the treatment of K-RAS-induced lung cancer and leukemia; and (2) To test the hypothesis that inactivation of FTase or ICMT will ameliorate disease phenotypes of progeria. I have developed genetic strategies to produce lung cancer or leukemia in mice by activating an oncogenic K-RAS and simultaneously inactivating different CAAX processing enzymes. I will also inactivate several CAAX processing enzymes in mice with progeria—both before the emergence of phenotypes and after the development of advanced disease phenotypes. These experiments should reveal whether the absence of the different CAAX processing enzymes affects the onset, progression, or regression of cancer and progeria.
Max ERC Funding
1 689 600 €
Duration
Start date: 2008-06-01, End date: 2013-05-31
Project acronym CurvedSusy
Project Dynamics of Supersymmetry in Curved Space
Researcher (PI) Guido Festuccia
Host Institution (HI) UPPSALA UNIVERSITET
Call Details Starting Grant (StG), PE2, ERC-2014-STG
Summary Quantum field theory provides a theoretical framework to explain quantitatively natural phenomena as diverse as the fluctuations in the cosmic microwave background, superconductivity, and elementary particle interactions in colliders. Even if we use quantum field theories in different settings, their structure and dynamics are still largely mysterious. Weakly coupled systems can be studied perturbatively, however many natural phenomena are characterized by strong self-interactions (e.g. high T superconductors, nuclear forces) and their analysis requires going beyond perturbation theory. Supersymmetric field theories are very interesting in this respect because they can be studied exactly even at strong coupling and their dynamics displays phenomena like confinement or the breaking of chiral symmetries that occur in nature and are very difficult to study analytically.
Recently it was realized that many interesting insights on the dynamics of supersymmetric field theories can be obtained by placing these theories in curved space preserving supersymmetry. These advances have opened new research avenues but also left many important questions unanswered. The aim of our research programme will be to clarify the dynamics of supersymmetric field theories in curved space and use this knowledge to establish new exact results for strongly coupled supersymmetric gauge theories. The novelty of our approach resides in the systematic use of the interplay between the physical properties of a supersymmetric theory and the geometrical properties of the space-time it lives in. The analytical results we will obtain, while derived for very symmetric theories, can be used as a guide in understanding the dynamics of many physical systems. Besides providing new tools to address the dynamics of quantum field theory at strong coupling this line of investigation could lead to new connections between Physics and Mathematics.
Summary
Quantum field theory provides a theoretical framework to explain quantitatively natural phenomena as diverse as the fluctuations in the cosmic microwave background, superconductivity, and elementary particle interactions in colliders. Even if we use quantum field theories in different settings, their structure and dynamics are still largely mysterious. Weakly coupled systems can be studied perturbatively, however many natural phenomena are characterized by strong self-interactions (e.g. high T superconductors, nuclear forces) and their analysis requires going beyond perturbation theory. Supersymmetric field theories are very interesting in this respect because they can be studied exactly even at strong coupling and their dynamics displays phenomena like confinement or the breaking of chiral symmetries that occur in nature and are very difficult to study analytically.
Recently it was realized that many interesting insights on the dynamics of supersymmetric field theories can be obtained by placing these theories in curved space preserving supersymmetry. These advances have opened new research avenues but also left many important questions unanswered. The aim of our research programme will be to clarify the dynamics of supersymmetric field theories in curved space and use this knowledge to establish new exact results for strongly coupled supersymmetric gauge theories. The novelty of our approach resides in the systematic use of the interplay between the physical properties of a supersymmetric theory and the geometrical properties of the space-time it lives in. The analytical results we will obtain, while derived for very symmetric theories, can be used as a guide in understanding the dynamics of many physical systems. Besides providing new tools to address the dynamics of quantum field theory at strong coupling this line of investigation could lead to new connections between Physics and Mathematics.
Max ERC Funding
1 145 879 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym DII
Project The Design of International Institutions: Legitimacy, Effectiveness and Distribution in Global Governance
Researcher (PI) Jonas Tallberg
Host Institution (HI) STOCKHOLMS UNIVERSITET
Call Details Starting Grant (StG), SH2, ERC-2007-StG
Summary One of the most profound trends in global governance over the past two decades is the growing extent to which international institutions offer mechanisms for the participation of transnational actors. This project will explore two central research questions, pertaining to the causes and effects of this shift in the design of international institutions: (1) Why have international institutions increasingly opened up to transnational actor involvement? (2) What are the consequences of involving transnational actors for the democratic legitimacy, problem-solving effectiveness, and distributional effects of international institutions? These are research questions that previously have not been explored systematically in existing literatures on international institutional design, transnational actors in global governance, and democracy beyond the nation-state. This project opens up a new research agenda on the design of international institutions through an ambitious combination of novel theory development and comparative empirical research. Theoretically, the project develops and tests alternative hypotheses about the causes and effects of transnational participation in international policy-making. Empirically, the project explores the dynamics of transnational participation through comparative case studies of five major international institutions, supplemented with a large-n mapping of formal mechanisms of transnational access in a broader sample of institutions. The project will help to establish an internationally competitive research group of post-doc researchers and Ph.D. students devoted to international institutional design, and consolidate the position of the principal investigator as a leading researcher in this field.
Summary
One of the most profound trends in global governance over the past two decades is the growing extent to which international institutions offer mechanisms for the participation of transnational actors. This project will explore two central research questions, pertaining to the causes and effects of this shift in the design of international institutions: (1) Why have international institutions increasingly opened up to transnational actor involvement? (2) What are the consequences of involving transnational actors for the democratic legitimacy, problem-solving effectiveness, and distributional effects of international institutions? These are research questions that previously have not been explored systematically in existing literatures on international institutional design, transnational actors in global governance, and democracy beyond the nation-state. This project opens up a new research agenda on the design of international institutions through an ambitious combination of novel theory development and comparative empirical research. Theoretically, the project develops and tests alternative hypotheses about the causes and effects of transnational participation in international policy-making. Empirically, the project explores the dynamics of transnational participation through comparative case studies of five major international institutions, supplemented with a large-n mapping of formal mechanisms of transnational access in a broader sample of institutions. The project will help to establish an internationally competitive research group of post-doc researchers and Ph.D. students devoted to international institutional design, and consolidate the position of the principal investigator as a leading researcher in this field.
Max ERC Funding
1 651 200 €
Duration
Start date: 2009-01-01, End date: 2014-12-31
Project acronym ERIKLINDAHLERC2007
Project Multiscale and Distributed Computing Algorithms for Biomolecular Simulation and Efficient Free Energy Calculations
Researcher (PI) Erik Lindahl
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Call Details Starting Grant (StG), PE4, ERC-2007-StG
Summary The long-term goal of our research is to advance the state-of-the-art in molecular simulation algorithms by 4-5 orders of magnitude, particularly in the context of the GROMACS software we are developing. This is an immense challenge, but with huge potential rewards: it will be an amazing virtual microscope for basic chemistry, polymer and material science research; it could help us understand the molecular basis of diseases such as Creutzfeldt-Jacob, and it would enable rational design rather than random screening for future drugs. To realize it, we will focus on four critical topics: • ALGORITHMS FOR SIMULATION ON GRAPHICS AND OTHER STREAMING PROCESSORS: Graphics cards and the test Intel 80-core chip are not only the most powerful processors available, but this type of streaming architectures will power many supercomputers in 3-5 years, and it is thus critical that we design new “streamable” MD algorithms. • MULTISCALE MODELING: We will develop virtual-site-based methods to bridge atomic and mesoscopic dynamics, QM/MM, and mixed explicit/implicit solvent models with water layers around macromolecules. • MULTI-LEVEL PARALLEL & DISTRIBUTED SIMULATION: Distributed computing provides virtually infinite computer power, but has been limited to small systems. We will address this by combining SMP parallelization and Markov State Models that partition phase space into transition/local dynamics to enable distributed simulation of arbitrary systems. • EFFICIENT FREE ENERGY CALCULATIONS: We will design algorithms for multi-conformational parallel sampling, implement Bennett Acceptance Ratios in Gromacs, correction terms for PME lattice sums, and combine standard force fields with polarization/multipoles, e.g. Amoeba. We have a very strong track record of converting methodological advances into applications, and the results will have impact on a wide range of fields from biomolecules and polymer science through material simulations and nanotechnology.
Summary
The long-term goal of our research is to advance the state-of-the-art in molecular simulation algorithms by 4-5 orders of magnitude, particularly in the context of the GROMACS software we are developing. This is an immense challenge, but with huge potential rewards: it will be an amazing virtual microscope for basic chemistry, polymer and material science research; it could help us understand the molecular basis of diseases such as Creutzfeldt-Jacob, and it would enable rational design rather than random screening for future drugs. To realize it, we will focus on four critical topics: • ALGORITHMS FOR SIMULATION ON GRAPHICS AND OTHER STREAMING PROCESSORS: Graphics cards and the test Intel 80-core chip are not only the most powerful processors available, but this type of streaming architectures will power many supercomputers in 3-5 years, and it is thus critical that we design new “streamable” MD algorithms. • MULTISCALE MODELING: We will develop virtual-site-based methods to bridge atomic and mesoscopic dynamics, QM/MM, and mixed explicit/implicit solvent models with water layers around macromolecules. • MULTI-LEVEL PARALLEL & DISTRIBUTED SIMULATION: Distributed computing provides virtually infinite computer power, but has been limited to small systems. We will address this by combining SMP parallelization and Markov State Models that partition phase space into transition/local dynamics to enable distributed simulation of arbitrary systems. • EFFICIENT FREE ENERGY CALCULATIONS: We will design algorithms for multi-conformational parallel sampling, implement Bennett Acceptance Ratios in Gromacs, correction terms for PME lattice sums, and combine standard force fields with polarization/multipoles, e.g. Amoeba. We have a very strong track record of converting methodological advances into applications, and the results will have impact on a wide range of fields from biomolecules and polymer science through material simulations and nanotechnology.
Max ERC Funding
992 413 €
Duration
Start date: 2008-09-01, End date: 2013-08-31
Project acronym GENOMIC STABILITY
Project Genomic stability -chromosome segregation and repair
Researcher (PI) Camilla Björkegren Sjögren
Host Institution (HI) KAROLINSKA INSTITUTET
Call Details Starting Grant (StG), LS1, ERC-2007-StG
Summary The eukaryotic genome combines a highly dynamic nature with stable transmission of genetic information from mother to daughter cells. This is achieved by a plethora of protein networks regulating processes such as chromosome duplication, segregation and repair. The principal aim of our research is to determine the molecular interplay between chromosome segregation and repair. Accurate execution of these two events is crucial for the maintenance of genome stability, which in turn is essential for life. Additionally, erroneous segregation or repair leads to chromosomal aberrations that are linked to tumor formation and human developmental syndromes. Thus, our investigations are not only crucial in a basic research perspective, but important also for the understanding of the causes of human disease. The research is based on the budding yeast model system, and combines genome-wide analysis of protein-chromosome interactions with cell-based experimental systems. Our investigations have until now revealed that chromosome segregation and repair are directly linked through two evolutionary conserved SMC (Structural Maintenance of Chromosomes) protein complexes, Cohesin and the Smc5/6 complex. The project now further explores the molecular details of this connection, bringing light into this unexplored area of research, and deciphering the cellular defense against genomic alterations connected to cancer and developmental diseases.
Summary
The eukaryotic genome combines a highly dynamic nature with stable transmission of genetic information from mother to daughter cells. This is achieved by a plethora of protein networks regulating processes such as chromosome duplication, segregation and repair. The principal aim of our research is to determine the molecular interplay between chromosome segregation and repair. Accurate execution of these two events is crucial for the maintenance of genome stability, which in turn is essential for life. Additionally, erroneous segregation or repair leads to chromosomal aberrations that are linked to tumor formation and human developmental syndromes. Thus, our investigations are not only crucial in a basic research perspective, but important also for the understanding of the causes of human disease. The research is based on the budding yeast model system, and combines genome-wide analysis of protein-chromosome interactions with cell-based experimental systems. Our investigations have until now revealed that chromosome segregation and repair are directly linked through two evolutionary conserved SMC (Structural Maintenance of Chromosomes) protein complexes, Cohesin and the Smc5/6 complex. The project now further explores the molecular details of this connection, bringing light into this unexplored area of research, and deciphering the cellular defense against genomic alterations connected to cancer and developmental diseases.
Max ERC Funding
900 000 €
Duration
Start date: 2008-09-01, End date: 2013-08-31
Project acronym GLOBALVISION
Project Global Optimization Methods in Computer Vision, Pattern Recognition and Medical Imaging
Researcher (PI) Fredrik Kahl
Host Institution (HI) LUNDS UNIVERSITET
Call Details Starting Grant (StG), PE5, ERC-2007-StG
Summary Computer vision concerns itself with understanding the real world through the analysis of images. Typical problems are object recognition, medical image segmentation, geometric reconstruction problems and navigation of autonomous vehicles. Such problems often lead to complicated optimization problems with a mixture of discrete and continuous variables, or even infinite dimensional variables in terms of curves and surfaces. Today, state-of-the-art in solving these problems generally relies on heuristic methods that generate only local optima of various qualities. During the last few years, work by the applicant, co-workers, and others has opened new possibilities. This research project builds on this. We will in this project focus on developing new global optimization methods for computing high-quality solutions for a broad class of problems. A guiding principle will be to relax the original, complicated problem to an approximate, simpler one to which globally optimal solutions can more easily be computed. Technically, this relaxed problem often is convex. A crucial point in this approach is to estimate the quality of the exact solution of the approximate problem compared to the (unknown) global optimum of the original problem. Preliminary results have been well received by the research community and we now wish to extend this work to more difficult and more general problem settings, resulting in thorough re-examination of algorithms used widely in different and trans-disciplinary fields. This project is to be considered as a basic research project with relevance to industry. The expected outcome is new knowledge spread to a wide community through scientific papers published at international journals and conferences as well as publicly available software.
Summary
Computer vision concerns itself with understanding the real world through the analysis of images. Typical problems are object recognition, medical image segmentation, geometric reconstruction problems and navigation of autonomous vehicles. Such problems often lead to complicated optimization problems with a mixture of discrete and continuous variables, or even infinite dimensional variables in terms of curves and surfaces. Today, state-of-the-art in solving these problems generally relies on heuristic methods that generate only local optima of various qualities. During the last few years, work by the applicant, co-workers, and others has opened new possibilities. This research project builds on this. We will in this project focus on developing new global optimization methods for computing high-quality solutions for a broad class of problems. A guiding principle will be to relax the original, complicated problem to an approximate, simpler one to which globally optimal solutions can more easily be computed. Technically, this relaxed problem often is convex. A crucial point in this approach is to estimate the quality of the exact solution of the approximate problem compared to the (unknown) global optimum of the original problem. Preliminary results have been well received by the research community and we now wish to extend this work to more difficult and more general problem settings, resulting in thorough re-examination of algorithms used widely in different and trans-disciplinary fields. This project is to be considered as a basic research project with relevance to industry. The expected outcome is new knowledge spread to a wide community through scientific papers published at international journals and conferences as well as publicly available software.
Max ERC Funding
1 440 000 €
Duration
Start date: 2008-07-01, End date: 2013-06-30
Project acronym INTESTINANOS
Project Intestinal Lipoidal Nanostructures - A Lipid Bridge to Increased Drug Delivery
Researcher (PI) Christel Anna Sofie Bergstrom
Host Institution (HI) UPPSALA UNIVERSITET
Call Details Starting Grant (StG), LS7, ERC-2014-STG
Summary My research program explores molecular interplay between drug, dosage form and the complex environment of the gastrointestinal tract (GIT). Drug molecules currently being discovered to cure e.g. CNS diseases, cancer and the metabolic syndrome show poor water solubility and 70-90% of recently discovered drugs have too poor solubility to allow absorption from the GIT. For such compounds the dosage form can significantly improve the absorption. My long-term goal is to establish a computational platform that predicts, from molecular structures and computational tools, the development potential of drug molecules to well-functioning orally administered medicines. A major gap to understand drug performance in the intestine is the poor knowledge of the dynamics of solubilizing lipoidal nanostructures (micelles, vesicles, oil droplets) present in the fluid. This project explores restructuring of these lipid colloids in response to intake of food or dosage forms, enzymatic digestion, absorption and transit along the GIT. Novel experimental tools are developed to reveal the impact of these nanostructures on drug solubilization, supersaturation and likelihood of precipitation in vivo, all being important for drug absorption. The experimental results are fed into in silico models taking use of Molecular Dynamics simulations to develop a computational platform predicting drug performance in the dynamic intestinal milieu. The novel tools designed herein will allow dosage forms that improve performance and increase drug absorption after oral administration to, for the first time, be designed by computational means. The results of this project, in particular the novel in silico tools exploring rearrangement of lipoidal nanostructures, are highly important to related areas such as GIT disease models and food processing but also have wider applications in e.g. studies of intracellular vesicle rearrangements and transport processes in plants.
Summary
My research program explores molecular interplay between drug, dosage form and the complex environment of the gastrointestinal tract (GIT). Drug molecules currently being discovered to cure e.g. CNS diseases, cancer and the metabolic syndrome show poor water solubility and 70-90% of recently discovered drugs have too poor solubility to allow absorption from the GIT. For such compounds the dosage form can significantly improve the absorption. My long-term goal is to establish a computational platform that predicts, from molecular structures and computational tools, the development potential of drug molecules to well-functioning orally administered medicines. A major gap to understand drug performance in the intestine is the poor knowledge of the dynamics of solubilizing lipoidal nanostructures (micelles, vesicles, oil droplets) present in the fluid. This project explores restructuring of these lipid colloids in response to intake of food or dosage forms, enzymatic digestion, absorption and transit along the GIT. Novel experimental tools are developed to reveal the impact of these nanostructures on drug solubilization, supersaturation and likelihood of precipitation in vivo, all being important for drug absorption. The experimental results are fed into in silico models taking use of Molecular Dynamics simulations to develop a computational platform predicting drug performance in the dynamic intestinal milieu. The novel tools designed herein will allow dosage forms that improve performance and increase drug absorption after oral administration to, for the first time, be designed by computational means. The results of this project, in particular the novel in silico tools exploring rearrangement of lipoidal nanostructures, are highly important to related areas such as GIT disease models and food processing but also have wider applications in e.g. studies of intracellular vesicle rearrangements and transport processes in plants.
Max ERC Funding
1 706 250 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym MEDIA AND POLICY
Project The impact of mass media on public policy
Researcher (PI) David Strömberg
Host Institution (HI) STOCKHOLMS UNIVERSITET
Call Details Starting Grant (StG), SH1, ERC-2007-StG
Summary This project will study political economics issues, that is, how public policies are influenced by political considerations. The emphasis is on the mass media's role in shaping government policies. A smaller part will also analyze how different political institutions and economic outcomes influence policy and the impact of extreme weather events. The project will mainly be empirical, using statistical methods with a focus on identifying causal effects, rather than correlations. The study of media effects will analyze the political impact of having a press actively covering politics. This is an important issue, largely unanswered because the presence of an active press is endogenous to things like corruption and voter information. We will address this question in the special case of media coverage of US Congressional elections. To identify the effect of news, we will use the fact that the amount of coverage is driven to a large extent by the coincidental match between media markets and congressional districts. We intend to analyze the effect of active press coverage on, (i) voter information, (ii) politicians actions, and (iii) federal funds per capita. The project will also investigate how political institutions and economic outcomes influences the health impacts (such as mortality among old and infants) of weather extremes. Historical weather data at a very detailed geographical level will be combined with socio-economic data in a panel (longitudinal) form. This is joint work with meteorologists who will construct historical weather data at fine grids across the globe. The part dealing with structural political economics aims to develop a framework for investigating the effects of institutions on economic policy. In existing work, there is a disconnect between the theoretical modelling and empirical applications. The aim is to close this gap.
Summary
This project will study political economics issues, that is, how public policies are influenced by political considerations. The emphasis is on the mass media's role in shaping government policies. A smaller part will also analyze how different political institutions and economic outcomes influence policy and the impact of extreme weather events. The project will mainly be empirical, using statistical methods with a focus on identifying causal effects, rather than correlations. The study of media effects will analyze the political impact of having a press actively covering politics. This is an important issue, largely unanswered because the presence of an active press is endogenous to things like corruption and voter information. We will address this question in the special case of media coverage of US Congressional elections. To identify the effect of news, we will use the fact that the amount of coverage is driven to a large extent by the coincidental match between media markets and congressional districts. We intend to analyze the effect of active press coverage on, (i) voter information, (ii) politicians actions, and (iii) federal funds per capita. The project will also investigate how political institutions and economic outcomes influences the health impacts (such as mortality among old and infants) of weather extremes. Historical weather data at a very detailed geographical level will be combined with socio-economic data in a panel (longitudinal) form. This is joint work with meteorologists who will construct historical weather data at fine grids across the globe. The part dealing with structural political economics aims to develop a framework for investigating the effects of institutions on economic policy. In existing work, there is a disconnect between the theoretical modelling and empirical applications. The aim is to close this gap.
Max ERC Funding
799 945 €
Duration
Start date: 2008-09-01, End date: 2014-08-31
