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 CANCERSTEM
Project Stem cells in epithelial cancer initiation and growth
Researcher (PI) Cédric Blanpain
Host Institution (HI) UNIVERSITE LIBRE DE BRUXELLES
Call Details Starting Grant (StG), LS6, ERC-2007-StG
Summary Cancer is the result of a multi-step process requiring the accumulation of mutations in several genes. For most cancers, the target cells of oncogenic mutations are unknown. Adult stem cells (SCs) might be the initial target cells as they self-renew for extended periods of time, providing increased opportunity to accumulate the mutations required for cancer formation. Certain cancers contain cells characteristics of SC with high self-renewal capacities and the ability to reform the parental tumor upon transplantation. However, whether the initial oncogenic mutations arise in normal stem cells or in more differentiated cells that re-acquire stem cell-like properties remains to be determined. The demonstration that SCs are the target cells of the initial transforming events and that cancers contain cells with SC characteristics await the development of tools allowing for the isolation and characterization of normal adult SCs. In most epithelia from which cancers naturally arise, such tools are not yet available. We have recently developed novel methods to specifically mark and isolate multipotent epidermal slow-cycling SCs, making it now possible to determine the role of SC during epithelial cancer formation. In this project, we will use mice epidermis as a model to define the role of SC in epithelial cancer initiation and growth. Specifically, we will determine whether epithelial SCs are the initial target cells of oncogenic mutations during skin cancer formation, whether oncogenic mutations lead preferentially to skin cancer when they arise in SC rather than in more committed cells and whether cancer stem cells contribute to epithelial tumor growth and relapse after therapy.
Summary
Cancer is the result of a multi-step process requiring the accumulation of mutations in several genes. For most cancers, the target cells of oncogenic mutations are unknown. Adult stem cells (SCs) might be the initial target cells as they self-renew for extended periods of time, providing increased opportunity to accumulate the mutations required for cancer formation. Certain cancers contain cells characteristics of SC with high self-renewal capacities and the ability to reform the parental tumor upon transplantation. However, whether the initial oncogenic mutations arise in normal stem cells or in more differentiated cells that re-acquire stem cell-like properties remains to be determined. The demonstration that SCs are the target cells of the initial transforming events and that cancers contain cells with SC characteristics await the development of tools allowing for the isolation and characterization of normal adult SCs. In most epithelia from which cancers naturally arise, such tools are not yet available. We have recently developed novel methods to specifically mark and isolate multipotent epidermal slow-cycling SCs, making it now possible to determine the role of SC during epithelial cancer formation. In this project, we will use mice epidermis as a model to define the role of SC in epithelial cancer initiation and growth. Specifically, we will determine whether epithelial SCs are the initial target cells of oncogenic mutations during skin cancer formation, whether oncogenic mutations lead preferentially to skin cancer when they arise in SC rather than in more committed cells and whether cancer stem cells contribute to epithelial tumor growth and relapse after therapy.
Max ERC Funding
1 600 000 €
Duration
Start date: 2008-07-01, End date: 2013-12-31
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 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 IMAGINED
Project Integrated Multi-disciplinary Approach to Gain INsight into Endothelial Diversity
Researcher (PI) Aernout Luttun
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Starting Grant (StG), LS6, ERC-2007-StG
Summary Endothelial cells (EC) lining the inside of blood/lymphatic vessels in different organs show significant heterogeneity caused by cell-intrinsic and -extrinsic factors. While intrinsic properties are preserved in vitro, EC-extrinsic characteristics are lost upon isolation from the in vivo context. Thus, getting a grasp on EC diversity requires an approach that integrates EC-intrinsic and -extrinsic cues. EC heterogeneity likely forms the basis of vessel-type restricted disorders and may explain the side effects and limited success of ‘broad-spectrum’ (anti-)angiogenic therapies. Also, EC progenitor-based revascularization studies have not asked whether cells acquire the desired EC phenotype once engrafted in diseased tissue where appropriate environmental cues are lacking. Unraveling mechanisms of EC heterogeneity should allow designing tailor-made therapies, which remains the main challenge in curing vessel-related disease. This research program proposes to use an unprecedented integrated in vitro/in vivo multi-disciplinary approach based on stem/progenitor cells and small animal models to: (i) expand our knowledge of EC diversity; (ii) exploit that knowledge to design specialized vascular therapies for (lymph)vascular disorders. In phase 1, gene-profiles (‘blueprints’) will be obtained by micro-array on EC isolated from various organs and macrovessels of different species with (intrinsic blueprint) or without (extrinsic blueprint) further culture. In phase 2, (co-)culture techniques that simulate the in vivo context will be applied to generate EC with the desired blueprint and appropriate function/morphology, by EC differentiation from adult stem cells. In phase 3, information obtained from phase 1/2 will be validated in vivo by (i) testing the expression profile of selected blueprint-genes, (ii) by morpholino knock-down of these genes in zebrafish, (iii) by transplanting stem cells, pre-specialized or not, into models of vascular bed or organ-specific disorders.
Summary
Endothelial cells (EC) lining the inside of blood/lymphatic vessels in different organs show significant heterogeneity caused by cell-intrinsic and -extrinsic factors. While intrinsic properties are preserved in vitro, EC-extrinsic characteristics are lost upon isolation from the in vivo context. Thus, getting a grasp on EC diversity requires an approach that integrates EC-intrinsic and -extrinsic cues. EC heterogeneity likely forms the basis of vessel-type restricted disorders and may explain the side effects and limited success of ‘broad-spectrum’ (anti-)angiogenic therapies. Also, EC progenitor-based revascularization studies have not asked whether cells acquire the desired EC phenotype once engrafted in diseased tissue where appropriate environmental cues are lacking. Unraveling mechanisms of EC heterogeneity should allow designing tailor-made therapies, which remains the main challenge in curing vessel-related disease. This research program proposes to use an unprecedented integrated in vitro/in vivo multi-disciplinary approach based on stem/progenitor cells and small animal models to: (i) expand our knowledge of EC diversity; (ii) exploit that knowledge to design specialized vascular therapies for (lymph)vascular disorders. In phase 1, gene-profiles (‘blueprints’) will be obtained by micro-array on EC isolated from various organs and macrovessels of different species with (intrinsic blueprint) or without (extrinsic blueprint) further culture. In phase 2, (co-)culture techniques that simulate the in vivo context will be applied to generate EC with the desired blueprint and appropriate function/morphology, by EC differentiation from adult stem cells. In phase 3, information obtained from phase 1/2 will be validated in vivo by (i) testing the expression profile of selected blueprint-genes, (ii) by morpholino knock-down of these genes in zebrafish, (iii) by transplanting stem cells, pre-specialized or not, into models of vascular bed or organ-specific disorders.
Max ERC Funding
1 616 719 €
Duration
Start date: 2008-10-01, End date: 2013-09-30
Project acronym MOLTALL
Project Molecularly targeted therapy for T cell acute lymphoblastic leukemia
Researcher (PI) Jan Cools
Host Institution (HI) VIB
Call Details Starting Grant (StG), LS6, ERC-2007-StG
Summary T cell acute lymphoblastic leukemia (T-ALL) is an aggressive T cell malignancy that is most common in children and adolescents. Our current understanding of the molecular genetics of T-ALL indicates that leukemic transformation of thymocytes is caused by the cooperation of mutations that affect proliferation, survival, cell cycle, differentiation and self renewal. Molecular analysis has identified a large number of T-ALL specific oncogenes, but the genetic defects that are implicated in the aberrant proliferation and survival of the leukemic cells remain largely unknown. It is the aim of this project to continue the molecular characterization of T-ALL using genome wide analyses, focused RNAi screens, and drug library screens to identify oncogenes that specifically provide proliferation and survival advantages, as well as other targets for therapy in T-ALL. In addition, we will study the cooperation of these oncogenes with other oncogenic events using in vitro and in vivo mouse models, and use those models for the development and characterization of novel therapeutics. This project will generate novel insights in the molecular pathogenesis of T-ALL and aims at translating this information towards novel targeted therapies.
Summary
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive T cell malignancy that is most common in children and adolescents. Our current understanding of the molecular genetics of T-ALL indicates that leukemic transformation of thymocytes is caused by the cooperation of mutations that affect proliferation, survival, cell cycle, differentiation and self renewal. Molecular analysis has identified a large number of T-ALL specific oncogenes, but the genetic defects that are implicated in the aberrant proliferation and survival of the leukemic cells remain largely unknown. It is the aim of this project to continue the molecular characterization of T-ALL using genome wide analyses, focused RNAi screens, and drug library screens to identify oncogenes that specifically provide proliferation and survival advantages, as well as other targets for therapy in T-ALL. In addition, we will study the cooperation of these oncogenes with other oncogenic events using in vitro and in vivo mouse models, and use those models for the development and characterization of novel therapeutics. This project will generate novel insights in the molecular pathogenesis of T-ALL and aims at translating this information towards novel targeted therapies.
Max ERC Funding
1 384 632 €
Duration
Start date: 2008-10-01, End date: 2013-09-30
Project acronym NANOFIB
Project Nano fibrous materials - structure, design and application
Researcher (PI) Christian Clasen
Host Institution (HI) KATHOLIEKE UNIVERSITEIT LEUVEN
Call Details Starting Grant (StG), PE6, ERC-2007-StG
Summary The performance and physical attributes of a material and product can be tailored to so far unmatched material strengths and properties by creating new nano fibrous structures from polymers by electrospinning. The electrospinning process uses an electric field to produce charged jets of polymer solutions or melts. Bending instabilities of the jet, caused by the surface charge, lead to extremely high local extension rates of the jet and produce fibres with diameters of the order of a few nanometer that consist of highly aligned polymer strands. However, the biggest unsolved problem of the electrospinning process is the sensitive equilibrium between surface tension, viscosity, elasticity and conductivity of the polymer solutions. These are controlled by molecular parameters as the molar mass, chemical microstructure, conformation in solution or supramolecular structures via intermolecular interactions. The optimal combination of these parameters is, as yet, unknown. Within this project, a novel and unique technical platform will be developed and installed, that is generally capable to image and analyse high speed free surface flows in miniaturised dimensions. This platform will then be utilized to analyse electrospinning process parameters and to connect them to the material properties and the molecular structure of the polymer solution. Only such a fundamental understanding of the relation of these properties to the flow and mass transfer phenomena on the micro-time and -dimensional scale will allow to design in the second part of this project the required structural and material properties of nano-scale fibres for: -novel fibre/matrix composites for the creation of ultra-high-strength hydrogel membranes; -short fibre morphologies created by a novel controlled disruptive spinning process at the boundaries of the parameter space; -tailoring of fibre properties from renewable resources by modification of the chemical side-chain structure of polysaccharides.
Summary
The performance and physical attributes of a material and product can be tailored to so far unmatched material strengths and properties by creating new nano fibrous structures from polymers by electrospinning. The electrospinning process uses an electric field to produce charged jets of polymer solutions or melts. Bending instabilities of the jet, caused by the surface charge, lead to extremely high local extension rates of the jet and produce fibres with diameters of the order of a few nanometer that consist of highly aligned polymer strands. However, the biggest unsolved problem of the electrospinning process is the sensitive equilibrium between surface tension, viscosity, elasticity and conductivity of the polymer solutions. These are controlled by molecular parameters as the molar mass, chemical microstructure, conformation in solution or supramolecular structures via intermolecular interactions. The optimal combination of these parameters is, as yet, unknown. Within this project, a novel and unique technical platform will be developed and installed, that is generally capable to image and analyse high speed free surface flows in miniaturised dimensions. This platform will then be utilized to analyse electrospinning process parameters and to connect them to the material properties and the molecular structure of the polymer solution. Only such a fundamental understanding of the relation of these properties to the flow and mass transfer phenomena on the micro-time and -dimensional scale will allow to design in the second part of this project the required structural and material properties of nano-scale fibres for: -novel fibre/matrix composites for the creation of ultra-high-strength hydrogel membranes; -short fibre morphologies created by a novel controlled disruptive spinning process at the boundaries of the parameter space; -tailoring of fibre properties from renewable resources by modification of the chemical side-chain structure of polysaccharides.
Max ERC Funding
1 228 736 €
Duration
Start date: 2008-07-01, End date: 2013-06-30
Project acronym PHOTOCHROMES
Project Photochromic Systems for Solid State Molecular Electronic Devices and Light-Activated Cancer Drugs
Researcher (PI) Joakim Andréasson
Host Institution (HI) CHALMERS TEKNISKA HOEGSKOLA AB
Call Details Starting Grant (StG), PE4, ERC-2007-StG
Summary Photochromic molecules, or photochromes, can be reversibly isomerized between two thermally stable forms by exposure to light of different wavelengths. Upon isomerization, properties such as excitation energies, redox properties, charge distribution, and structure experience significant changes. These changes can be harnessed to switch “on” or “off” the action of a variety of photophysical processes in the photochromic constructs, e.g., energy and electron transfer. Until now, the focus of my research has been to show proof of principle for a large selection of molecule-based photonically controlled logic devices (solution based) with the functional basis in the switching of the transfer processes mentioned above. Now, I wish to extend the study to include experiments in the solid state, e.g., polymer matrices. Taking the step into doing solid state chemistry is not only a prerequisite for any real-world application. It will also allow for experiments that cannot be performed in fluid solution, such as aligning molecules in a stretched film for chemistry with polarized light, and immobilization of molecules for selective addressing in a three-dimensional array of volume elements. Furthermore, I intend to investigate the possibility to photonically control the membrane penetrating and the DNA-binding abilities of photochromes, aiming at, in a long-term perspective, light-activated cancer drugs. Due to the fact that both the structure and the charge distribution of a photochrome may change drastically upon isomerization, one of the two isomeric forms is often suitable for penetrating a membrane. Inside the membrane, e.g., in a cell, the photochrome can be photo-isomerized to a structure with high affinity for strong binding to DNA. Upon binding, transcription is inhibited and the cell dies. If desired, pH-sensitivity and two-photon processes could be used to further increase the selectivity in addressing very specific regions of the body, such as a tumor.
Summary
Photochromic molecules, or photochromes, can be reversibly isomerized between two thermally stable forms by exposure to light of different wavelengths. Upon isomerization, properties such as excitation energies, redox properties, charge distribution, and structure experience significant changes. These changes can be harnessed to switch “on” or “off” the action of a variety of photophysical processes in the photochromic constructs, e.g., energy and electron transfer. Until now, the focus of my research has been to show proof of principle for a large selection of molecule-based photonically controlled logic devices (solution based) with the functional basis in the switching of the transfer processes mentioned above. Now, I wish to extend the study to include experiments in the solid state, e.g., polymer matrices. Taking the step into doing solid state chemistry is not only a prerequisite for any real-world application. It will also allow for experiments that cannot be performed in fluid solution, such as aligning molecules in a stretched film for chemistry with polarized light, and immobilization of molecules for selective addressing in a three-dimensional array of volume elements. Furthermore, I intend to investigate the possibility to photonically control the membrane penetrating and the DNA-binding abilities of photochromes, aiming at, in a long-term perspective, light-activated cancer drugs. Due to the fact that both the structure and the charge distribution of a photochrome may change drastically upon isomerization, one of the two isomeric forms is often suitable for penetrating a membrane. Inside the membrane, e.g., in a cell, the photochrome can be photo-isomerized to a structure with high affinity for strong binding to DNA. Upon binding, transcription is inhibited and the cell dies. If desired, pH-sensitivity and two-photon processes could be used to further increase the selectivity in addressing very specific regions of the body, such as a tumor.
Max ERC Funding
1 000 000 €
Duration
Start date: 2008-09-01, End date: 2013-08-31
Project acronym QPQV
Project Quantum plasmas and the quantum vacuum: New vistas in physics
Researcher (PI) Mattias Marklund
Host Institution (HI) UMEA UNIVERSITET
Call Details Starting Grant (StG), PE2, ERC-2007-StG
Summary The quantum vacuum constitutes a highly nontrivial medium, in which complex nonlinear processes, such as pair production and photon splitting, can take place. These processes will yield measurable alterations to classical electromagnetic wave dynamics and laser-matter interactions using the next-generation laser systems. It has been suggested that this could even give rise to self-compression of electromagnetic pulses in vacuum, and therefore produce intensities above the laser limit. This gives the possibility of anti-matter production, light splitting, and light collisions, that could be of importance for testing the invariance properties of the laws of physics. Furthermore, the properties of the quantum vacuum holds the key to a fundamental understanding of highly magnetized stars, the relation of spacetime dynamics to thermodynamics, and could be used to obtain information about e.g. dark matter candidates. Thus, the effects of the quantum vacuum will be noticeable both on a practical level, in future high intensity field experiments and applications, as well as at the level of basic research, providing crucial information about the properties of the laws of physics. The aim of this proposal is manifold. Using high intensity electromagnetic field generation different aspects of the quantum vacuum will be probed. The experimental investigation of the Unruh effect will yield insight into black hole physics and effects of spacetime structure on quantum field theory. The possibility to detect elastic scattering among photons would open up a completely new branch in science and deepen our understanding of the laws of physics. Moreover, using state-of-the-art laser facilities, methods for probing extreme plasmas, where quantum particle dynamics and the nonlinear quantum vacuum are important, will be developed. This holds promising applications as lasers approach entirely new intensity level in the near future.
Summary
The quantum vacuum constitutes a highly nontrivial medium, in which complex nonlinear processes, such as pair production and photon splitting, can take place. These processes will yield measurable alterations to classical electromagnetic wave dynamics and laser-matter interactions using the next-generation laser systems. It has been suggested that this could even give rise to self-compression of electromagnetic pulses in vacuum, and therefore produce intensities above the laser limit. This gives the possibility of anti-matter production, light splitting, and light collisions, that could be of importance for testing the invariance properties of the laws of physics. Furthermore, the properties of the quantum vacuum holds the key to a fundamental understanding of highly magnetized stars, the relation of spacetime dynamics to thermodynamics, and could be used to obtain information about e.g. dark matter candidates. Thus, the effects of the quantum vacuum will be noticeable both on a practical level, in future high intensity field experiments and applications, as well as at the level of basic research, providing crucial information about the properties of the laws of physics. The aim of this proposal is manifold. Using high intensity electromagnetic field generation different aspects of the quantum vacuum will be probed. The experimental investigation of the Unruh effect will yield insight into black hole physics and effects of spacetime structure on quantum field theory. The possibility to detect elastic scattering among photons would open up a completely new branch in science and deepen our understanding of the laws of physics. Moreover, using state-of-the-art laser facilities, methods for probing extreme plasmas, where quantum particle dynamics and the nonlinear quantum vacuum are important, will be developed. This holds promising applications as lasers approach entirely new intensity level in the near future.
Max ERC Funding
1 000 000 €
Duration
Start date: 2008-08-01, End date: 2013-07-31
