Project acronym AGALT
Project Asymptotic Geometric Analysis and Learning Theory
Researcher (PI) Shahar Mendelson
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), PE1, ERC-2007-StG
Summary In a typical learning problem one tries to approximate an unknown function by a function from a given class using random data, sampled according to an unknown measure. In this project we will be interested in parameters that govern the complexity of a learning problem. It turns out that this complexity is determined by the geometry of certain sets in high dimension that are connected to the given class (random coordinate projections of the class). Thus, one has to understand the structure of these sets as a function of the dimension - which is given by the cardinality of the random sample. The resulting analysis leads to many theoretical questions in Asymptotic Geometric Analysis, Probability (most notably, Empirical Processes Theory) and Combinatorics, which are of independent interest beyond the application to Learning Theory. Our main goal is to describe the role of various complexity parameters involved in a learning problem, to analyze the connections between them and to investigate the way they determine the geometry of the relevant high dimensional sets. Some of the questions we intend to tackle are well known open problems and making progress towards their solution will have a significant theoretical impact. Moreover, this project should lead to a more complete theory of learning and is likely to have some practical impact, for example, in the design of more efficient learning algorithms.
Summary
In a typical learning problem one tries to approximate an unknown function by a function from a given class using random data, sampled according to an unknown measure. In this project we will be interested in parameters that govern the complexity of a learning problem. It turns out that this complexity is determined by the geometry of certain sets in high dimension that are connected to the given class (random coordinate projections of the class). Thus, one has to understand the structure of these sets as a function of the dimension - which is given by the cardinality of the random sample. The resulting analysis leads to many theoretical questions in Asymptotic Geometric Analysis, Probability (most notably, Empirical Processes Theory) and Combinatorics, which are of independent interest beyond the application to Learning Theory. Our main goal is to describe the role of various complexity parameters involved in a learning problem, to analyze the connections between them and to investigate the way they determine the geometry of the relevant high dimensional sets. Some of the questions we intend to tackle are well known open problems and making progress towards their solution will have a significant theoretical impact. Moreover, this project should lead to a more complete theory of learning and is likely to have some practical impact, for example, in the design of more efficient learning algorithms.
Max ERC Funding
750 000 €
Duration
Start date: 2009-03-01, End date: 2014-02-28
Project acronym ASSESS
Project Episodic Mass Loss in the Most Massive Stars: Key to Understanding the Explosive Early Universe
Researcher (PI) Alceste BONANOS
Host Institution (HI) NATIONAL OBSERVATORY OF ATHENS
Call Details Consolidator Grant (CoG), PE9, ERC-2017-COG
Summary Massive stars dominate their surroundings during their short lifetimes, while their explosive deaths impact the chemical evolution and spatial cohesion of their hosts. After birth, their evolution is largely dictated by their ability to remove layers of hydrogen from their envelopes. Multiple lines of evidence are pointing to violent, episodic mass-loss events being responsible for removing a large part of the massive stellar envelope, especially in low-metallicity galaxies. Episodic mass loss, however, is not understood theoretically, neither accounted for in state-of-the-art models of stellar evolution, which has far-reaching consequences for many areas of astronomy. We aim to determine whether episodic mass loss is a dominant process in the evolution of the most massive stars by conducting the first extensive, multi-wavelength survey of evolved massive stars in the nearby Universe. The project hinges on the fact that mass-losing stars form dust and are bright in the mid-infrared. We plan to (i) derive physical parameters of a large sample of dusty, evolved targets and estimate the amount of ejected mass, (ii) constrain evolutionary models, (iii) quantify the duration and frequency of episodic mass loss as a function of metallicity. The approach involves applying machine-learning algorithms to existing multi-band and time-series photometry of luminous sources in ~25 nearby galaxies. Dusty, luminous evolved massive stars will thus be automatically classified and follow-up spectroscopy will be obtained for selected targets. Atmospheric and SED modeling will yield parameters and estimates of time-dependent mass loss for ~1000 luminous stars. The emerging trend for the ubiquity of episodic mass loss, if confirmed, will be key to understanding the explosive early Universe and will have profound consequences for low-metallicity stars, reionization, and the chemical evolution of galaxies.
Summary
Massive stars dominate their surroundings during their short lifetimes, while their explosive deaths impact the chemical evolution and spatial cohesion of their hosts. After birth, their evolution is largely dictated by their ability to remove layers of hydrogen from their envelopes. Multiple lines of evidence are pointing to violent, episodic mass-loss events being responsible for removing a large part of the massive stellar envelope, especially in low-metallicity galaxies. Episodic mass loss, however, is not understood theoretically, neither accounted for in state-of-the-art models of stellar evolution, which has far-reaching consequences for many areas of astronomy. We aim to determine whether episodic mass loss is a dominant process in the evolution of the most massive stars by conducting the first extensive, multi-wavelength survey of evolved massive stars in the nearby Universe. The project hinges on the fact that mass-losing stars form dust and are bright in the mid-infrared. We plan to (i) derive physical parameters of a large sample of dusty, evolved targets and estimate the amount of ejected mass, (ii) constrain evolutionary models, (iii) quantify the duration and frequency of episodic mass loss as a function of metallicity. The approach involves applying machine-learning algorithms to existing multi-band and time-series photometry of luminous sources in ~25 nearby galaxies. Dusty, luminous evolved massive stars will thus be automatically classified and follow-up spectroscopy will be obtained for selected targets. Atmospheric and SED modeling will yield parameters and estimates of time-dependent mass loss for ~1000 luminous stars. The emerging trend for the ubiquity of episodic mass loss, if confirmed, will be key to understanding the explosive early Universe and will have profound consequences for low-metallicity stars, reionization, and the chemical evolution of galaxies.
Max ERC Funding
1 128 750 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym BACTERIAL SPORES
Project Investigating the Nature of Bacterial Spores
Researcher (PI) Sigal Ben-Yehuda
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Starting Grant (StG), LS3, ERC-2007-StG
Summary When triggered by nutrient limitation, the Gram-positive bacterium Bacillus subtilis and its relatives enter a pathway of cellular differentiation culminating in the formation of a dormant cell type called a spore, the most resilient cell type known. Bacterial spores can survive for long periods of time and are able to endure extremes of heat, radiation and chemical assault. Remarkably, dormant spores can rapidly convert back to actively growing cells by a process called germination. Consequently, spore forming bacteria, including dangerous pathogens, (such as C. botulinum and B. anthracis) are highly resistant to antibacterial treatments and difficult to eradicate. Despite significant advances in our understanding of the process of spore formation, little is known about the nature of the mature spore. It is unrevealed how dormancy is maintained within the spore and how it is ceased, as the organization and the dynamics of the spore macromolecules remain obscure. The unusual biochemical and biophysical characteristics of the dormant spore make it a challenging biological system to investigate using conventional methods, and thus set the need to develop innovative approaches to study spore biology. We propose to explore the nature of spores by using B. subtilis as a primary experimental system. We intend to: (1) define the architecture of the spore chromosome, (2) track the complexity and fate of mRNA and protein molecules during sporulation, dormancy and germination, (3) revisit the basic notion of the spore dormancy (is it metabolically inert?), (4) compare the characteristics of bacilli spores from diverse ecophysiological groups, (5) investigate the features of spores belonging to distant bacterial genera, (6) generate an integrative database that categorizes the molecular features of spores. Our study will provide original insights and introduce novel concepts to the field of spore biology and may help devise innovative ways to combat spore forming pathogens.
Summary
When triggered by nutrient limitation, the Gram-positive bacterium Bacillus subtilis and its relatives enter a pathway of cellular differentiation culminating in the formation of a dormant cell type called a spore, the most resilient cell type known. Bacterial spores can survive for long periods of time and are able to endure extremes of heat, radiation and chemical assault. Remarkably, dormant spores can rapidly convert back to actively growing cells by a process called germination. Consequently, spore forming bacteria, including dangerous pathogens, (such as C. botulinum and B. anthracis) are highly resistant to antibacterial treatments and difficult to eradicate. Despite significant advances in our understanding of the process of spore formation, little is known about the nature of the mature spore. It is unrevealed how dormancy is maintained within the spore and how it is ceased, as the organization and the dynamics of the spore macromolecules remain obscure. The unusual biochemical and biophysical characteristics of the dormant spore make it a challenging biological system to investigate using conventional methods, and thus set the need to develop innovative approaches to study spore biology. We propose to explore the nature of spores by using B. subtilis as a primary experimental system. We intend to: (1) define the architecture of the spore chromosome, (2) track the complexity and fate of mRNA and protein molecules during sporulation, dormancy and germination, (3) revisit the basic notion of the spore dormancy (is it metabolically inert?), (4) compare the characteristics of bacilli spores from diverse ecophysiological groups, (5) investigate the features of spores belonging to distant bacterial genera, (6) generate an integrative database that categorizes the molecular features of spores. Our study will provide original insights and introduce novel concepts to the field of spore biology and may help devise innovative ways to combat spore forming pathogens.
Max ERC Funding
1 630 000 €
Duration
Start date: 2008-10-01, End date: 2013-09-30
Project acronym BANDWIDTH
Project The cost of limited communication bandwidth in distributed computing
Researcher (PI) Keren CENSOR-HILLEL
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), PE6, ERC-2017-STG
Summary Distributed systems underlie many modern technologies, a prime example being the Internet. The ever-increasing abundance of distributed systems necessitates their design and usage to be backed by strong theoretical foundations.
A major challenge that distributed systems face is the lack of a central authority, which brings many aspects of uncertainty into the environment, in the form of unknown network topology or unpredictable dynamic behavior. A practical restriction of distributed systems, which is at the heart of this proposal, is the limited bandwidth available for communication between the network components.
A central family of distributed tasks is that of local tasks, which are informally described as tasks which are possible to solve by sending information through only a relatively small number of hops. A cornerstone example is the need to break symmetry and provide a better utilization of resources, which can be obtained by the task of producing a valid coloring of the nodes given some small number of colors. Amazingly, there are still huge gaps between the known upper and lower bounds for the complexity of many local tasks. This holds even if one allows powerful assumptions of unlimited bandwidth. While some known algorithms indeed use small messages, the complexity gaps are even larger compared to the unlimited bandwidth case. This is not a mere coincidence, and in fact the existing theoretical infrastructure is provably incapable of
giving stronger lower bounds for many local tasks under limited bandwidth.
This proposal zooms in on this crucial blind spot in the current literature on the theory of distributed computing, namely, the study of local tasks under limited bandwidth. The goal of this research is to produce fast algorithms for fundamental distributed local tasks under restricted bandwidth, as well as understand their limitations by providing lower bounds.
Summary
Distributed systems underlie many modern technologies, a prime example being the Internet. The ever-increasing abundance of distributed systems necessitates their design and usage to be backed by strong theoretical foundations.
A major challenge that distributed systems face is the lack of a central authority, which brings many aspects of uncertainty into the environment, in the form of unknown network topology or unpredictable dynamic behavior. A practical restriction of distributed systems, which is at the heart of this proposal, is the limited bandwidth available for communication between the network components.
A central family of distributed tasks is that of local tasks, which are informally described as tasks which are possible to solve by sending information through only a relatively small number of hops. A cornerstone example is the need to break symmetry and provide a better utilization of resources, which can be obtained by the task of producing a valid coloring of the nodes given some small number of colors. Amazingly, there are still huge gaps between the known upper and lower bounds for the complexity of many local tasks. This holds even if one allows powerful assumptions of unlimited bandwidth. While some known algorithms indeed use small messages, the complexity gaps are even larger compared to the unlimited bandwidth case. This is not a mere coincidence, and in fact the existing theoretical infrastructure is provably incapable of
giving stronger lower bounds for many local tasks under limited bandwidth.
This proposal zooms in on this crucial blind spot in the current literature on the theory of distributed computing, namely, the study of local tasks under limited bandwidth. The goal of this research is to produce fast algorithms for fundamental distributed local tasks under restricted bandwidth, as well as understand their limitations by providing lower bounds.
Max ERC Funding
1 486 480 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym BioMet
Project Selective Functionalization of Saturated Hydrocarbons
Researcher (PI) Ilan MAREK
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Advanced Grant (AdG), PE5, ERC-2017-ADG
Summary Despite that C–H functionalization represents a paradigm shift from the standard logic of organic synthesis, the selective activation of non-functionalized alkanes has puzzled chemists for centuries and is always referred to one of the remaining major challenges in chemical sciences. Alkanes are inert compounds representing the major constituents of natural gas and petroleum. Converting these cheap and widely available hydrocarbon feedstocks into added-value intermediates would tremendously affect the field of chemistry. For long saturated hydrocarbons, one must distinguish between non-equivalent but chemically very similar alkane substrate C−H bonds, and for functionalization at the terminus position, one must favor activation of the stronger, primary C−H bonds at the expense of weaker and numerous secondary C-H bonds. The goal of this work is to develop a general principle in organic synthesis for the preparation of a wide variety of more complex molecular architectures from saturated hydrocarbons. In our approach, the alkane will first be transformed into an alkene that will subsequently be engaged in a metal-catalyzed hydrometalation/migration sequence. The first step of the sequence, ideally represented by the removal of two hydrogen atoms, will be performed by the use of a mutated strain of Rhodococcus. The position and geometry of the formed double bond has no effect on the second step of the reaction as the metal-catalyzed hydrometalation/migration will isomerize the double bond along the carbon skeleton to selectively produce the primary organometallic species. Trapping the resulting organometallic derivatives with a large variety of electrophiles will provide the desired functionalized alkane. This work will lead to the invention of new, selective and efficient processes for the utilization of simple hydrocarbons and valorize the synthetic potential of raw hydrocarbon feedstock for the environmentally benign production of new compounds and new materials.
Summary
Despite that C–H functionalization represents a paradigm shift from the standard logic of organic synthesis, the selective activation of non-functionalized alkanes has puzzled chemists for centuries and is always referred to one of the remaining major challenges in chemical sciences. Alkanes are inert compounds representing the major constituents of natural gas and petroleum. Converting these cheap and widely available hydrocarbon feedstocks into added-value intermediates would tremendously affect the field of chemistry. For long saturated hydrocarbons, one must distinguish between non-equivalent but chemically very similar alkane substrate C−H bonds, and for functionalization at the terminus position, one must favor activation of the stronger, primary C−H bonds at the expense of weaker and numerous secondary C-H bonds. The goal of this work is to develop a general principle in organic synthesis for the preparation of a wide variety of more complex molecular architectures from saturated hydrocarbons. In our approach, the alkane will first be transformed into an alkene that will subsequently be engaged in a metal-catalyzed hydrometalation/migration sequence. The first step of the sequence, ideally represented by the removal of two hydrogen atoms, will be performed by the use of a mutated strain of Rhodococcus. The position and geometry of the formed double bond has no effect on the second step of the reaction as the metal-catalyzed hydrometalation/migration will isomerize the double bond along the carbon skeleton to selectively produce the primary organometallic species. Trapping the resulting organometallic derivatives with a large variety of electrophiles will provide the desired functionalized alkane. This work will lead to the invention of new, selective and efficient processes for the utilization of simple hydrocarbons and valorize the synthetic potential of raw hydrocarbon feedstock for the environmentally benign production of new compounds and new materials.
Max ERC Funding
2 499 375 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym BIOSELFORGANIZATION
Project Biophysical aspects of self-organization in actin-based cell motility
Researcher (PI) Kinneret Magda Keren
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), PE3, ERC-2007-StG
Summary Cell motility is a fascinating dynamic process crucial for a wide variety of biological phenomena including defense against injury or infection, embryogenesis and cancer metastasis. A spatially extended, self-organized, mechanochemical machine consisting of numerous actin polymers, accessory proteins and molecular motors drives this process. This impressive assembly self-organizes over several orders of magnitude in both the temporal and spatial domains bridging from the fast dynamics of individual molecular-sized building blocks to the persistent motion of whole cells over minutes and hours. The molecular players involved in the process and the basic biochemical mechanisms are largely known. However, the principles governing the assembly of the motility apparatus, which involve an intricate interplay between biophysical processes and biochemical reactions, are still poorly understood. The proposed research is focused on investigating the biophysical aspects of the self-organization processes underlying cell motility and trying to adapt these processes to instill motility in artificial cells. Important biophysical characteristics of moving cells such as the intracellular fluid flow and membrane tension will be measured and their effect on the motility process will be examined, using fish epithelial keratocytes as a model system. The dynamics of the system will be further investigated by quantitatively analyzing the morphological and kinematic variation displayed by a population of cells and by an individual cell through time. Such measurements will feed into and direct the development of quantitative theoretical models. In parallel, I will work toward the development of a synthetic physical model system for cell motility by encapsulating the actin machinery in a cell-sized compartment. This synthetic system will allow cell motility to be studied in a simplified and controlled environment, detached from the complexity of the living cell.
Summary
Cell motility is a fascinating dynamic process crucial for a wide variety of biological phenomena including defense against injury or infection, embryogenesis and cancer metastasis. A spatially extended, self-organized, mechanochemical machine consisting of numerous actin polymers, accessory proteins and molecular motors drives this process. This impressive assembly self-organizes over several orders of magnitude in both the temporal and spatial domains bridging from the fast dynamics of individual molecular-sized building blocks to the persistent motion of whole cells over minutes and hours. The molecular players involved in the process and the basic biochemical mechanisms are largely known. However, the principles governing the assembly of the motility apparatus, which involve an intricate interplay between biophysical processes and biochemical reactions, are still poorly understood. The proposed research is focused on investigating the biophysical aspects of the self-organization processes underlying cell motility and trying to adapt these processes to instill motility in artificial cells. Important biophysical characteristics of moving cells such as the intracellular fluid flow and membrane tension will be measured and their effect on the motility process will be examined, using fish epithelial keratocytes as a model system. The dynamics of the system will be further investigated by quantitatively analyzing the morphological and kinematic variation displayed by a population of cells and by an individual cell through time. Such measurements will feed into and direct the development of quantitative theoretical models. In parallel, I will work toward the development of a synthetic physical model system for cell motility by encapsulating the actin machinery in a cell-sized compartment. This synthetic system will allow cell motility to be studied in a simplified and controlled environment, detached from the complexity of the living cell.
Max ERC Funding
900 000 €
Duration
Start date: 2008-08-01, End date: 2013-07-31
Project acronym BirNonArchGeom
Project Birational and non-archimedean geometries
Researcher (PI) Michael TEMKIN
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Consolidator Grant (CoG), PE1, ERC-2017-COG
Summary Resolution of singularities is one of classical, central and difficult areas of algebraic geometry, with a centennial history of intensive research and contributions of such great names as Zariski, Hironaka and Abhyankar. Nowadays, desingularization of schemes of characteristic zero is very well understood, while semistable reduction of morphisms and desingularization in positive characteristic are still waiting for major breakthroughs. In addition to the classical techniques with their triumph in characteristic zero, modern resolution of singularities includes de Jong's method of alterations, toroidal methods, formal analytic and non-archimedean methods, etc.
The aim of the proposed research is to study nearly all directions in resolution of singularities and semistable reduction, as well as the wild ramification phenomena, which are probably the main obstacle to transfer methods from characteristic zero to positive characteristic.
The methods of algebraic and non-archimedean geometries are intertwined in the proposal, though algebraic geometry is somewhat dominating, especially due to the new stack-theoretic techniques. It seems very probable that increasing the symbiosis between birational and non-archimedean geometries will be one of by-products of this research.
Summary
Resolution of singularities is one of classical, central and difficult areas of algebraic geometry, with a centennial history of intensive research and contributions of such great names as Zariski, Hironaka and Abhyankar. Nowadays, desingularization of schemes of characteristic zero is very well understood, while semistable reduction of morphisms and desingularization in positive characteristic are still waiting for major breakthroughs. In addition to the classical techniques with their triumph in characteristic zero, modern resolution of singularities includes de Jong's method of alterations, toroidal methods, formal analytic and non-archimedean methods, etc.
The aim of the proposed research is to study nearly all directions in resolution of singularities and semistable reduction, as well as the wild ramification phenomena, which are probably the main obstacle to transfer methods from characteristic zero to positive characteristic.
The methods of algebraic and non-archimedean geometries are intertwined in the proposal, though algebraic geometry is somewhat dominating, especially due to the new stack-theoretic techniques. It seems very probable that increasing the symbiosis between birational and non-archimedean geometries will be one of by-products of this research.
Max ERC Funding
1 365 600 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
Project acronym BRAINPLASTICITY
Project In vivo imaging of functional plasticity in the mammalian brain
Researcher (PI) Adi Mizrahi
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Starting Grant (StG), LS4, ERC-2007-StG
Summary "The dynamic nature of the brain operates at disparate time scales ranging from milliseconds to months. How do single neurons change over such long time scales? This question remains stubborn to answer in the field of brain plasticity mainly because of limited tools to study the physiology of single neurons over time in the complex environment of the brain. The research aim of this proposal is to reveal the physiological changes of single neurons in the mammalian brain over disparate time scales using time-lapse optical imaging. Specifically, we aim to establish a new team that will develop genetic and optical tools to probe the physiological activity of single neurons, in vivo. As a model system, we will study a unique neuronal population in the mammalian brain; the adult-born local neurons in the olfactory bulb. These neurons have tremendous potential to reveal how neurons develop and maintain in the intact brain because they are accessible both genetically and optically. By following the behavior of adult-born neurons in vivo we will discover how neurons mature and maintain over days and weeks. If our objectives will be met, this study has the potential to significantly ""raise the bar"" on how neuronal plasticity is studied and reveal some basic secrets of the ever changing mammalian brain."
Summary
"The dynamic nature of the brain operates at disparate time scales ranging from milliseconds to months. How do single neurons change over such long time scales? This question remains stubborn to answer in the field of brain plasticity mainly because of limited tools to study the physiology of single neurons over time in the complex environment of the brain. The research aim of this proposal is to reveal the physiological changes of single neurons in the mammalian brain over disparate time scales using time-lapse optical imaging. Specifically, we aim to establish a new team that will develop genetic and optical tools to probe the physiological activity of single neurons, in vivo. As a model system, we will study a unique neuronal population in the mammalian brain; the adult-born local neurons in the olfactory bulb. These neurons have tremendous potential to reveal how neurons develop and maintain in the intact brain because they are accessible both genetically and optically. By following the behavior of adult-born neurons in vivo we will discover how neurons mature and maintain over days and weeks. If our objectives will be met, this study has the potential to significantly ""raise the bar"" on how neuronal plasticity is studied and reveal some basic secrets of the ever changing mammalian brain."
Max ERC Funding
1 750 000 €
Duration
Start date: 2008-08-01, End date: 2013-07-31
Project acronym CardHeal
Project Novel strategies for mammalian cardiac repair
Researcher (PI) Eldad TZAHOR
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Advanced Grant (AdG), LS4, ERC-2017-ADG
Summary Recent ground-breaking studies by my team and others demonstrated that latent heart regeneration machinery can be awakened even in adult mammals. My lab’s main contribution is the identification of two, apparently different, molecular mechanisms for augmenting cardiac regeneration in adult mice. The first requires transient activation of ErbB2 signalling in cardiomyocytes and the second involves extra cellular matrix-driven signalling by the proteoglycan agrin. Impressively, both mechanisms promote a major regenerative response that, in turn, enhances cardiac repair. In CardHeal we will use the two powerful regenerative models to obtain a holistic view of cardiac regeneration and repair mechanisms in mammals (mice and pigs).
In Aim 1, we will explore the molecular mechanisms underlying our discovery that transient activation of ErbB2 in adult cardiomyocytes results in massive cardiomyocyte dedifferentiation and proliferation followed by new vessels formation, scar resolution and functional cardiac repair. Specific objectives focus on ErbB2-Yap/Hippo signalling during cardiac regeneration; ErbB2 activation in a chronic heart failure model; ErbB2-induced regenerative EMT-like process; and cardiomyocyte re-differentiation.
In Aim 2, we will investigate the therapeutic effects of agrin, whose administration into injured hearts of mice and pigs elicits a significant regenerative response. Specific objectives are matrix-related cardiac regenerative cues, modulation of the immune response, angiogenesis, matrix remodeling, and developing a preclinical, large animal model to study agrin efficacy for cardiac repair.
Interrogating the differences and similarities between our two regenerative models should give us a detailed roadmap for cardiac regenerative medicine by providing deeper knowledge of the regenerative process in the heart and pointing to novel targets for cardiac repair in human patients.
Summary
Recent ground-breaking studies by my team and others demonstrated that latent heart regeneration machinery can be awakened even in adult mammals. My lab’s main contribution is the identification of two, apparently different, molecular mechanisms for augmenting cardiac regeneration in adult mice. The first requires transient activation of ErbB2 signalling in cardiomyocytes and the second involves extra cellular matrix-driven signalling by the proteoglycan agrin. Impressively, both mechanisms promote a major regenerative response that, in turn, enhances cardiac repair. In CardHeal we will use the two powerful regenerative models to obtain a holistic view of cardiac regeneration and repair mechanisms in mammals (mice and pigs).
In Aim 1, we will explore the molecular mechanisms underlying our discovery that transient activation of ErbB2 in adult cardiomyocytes results in massive cardiomyocyte dedifferentiation and proliferation followed by new vessels formation, scar resolution and functional cardiac repair. Specific objectives focus on ErbB2-Yap/Hippo signalling during cardiac regeneration; ErbB2 activation in a chronic heart failure model; ErbB2-induced regenerative EMT-like process; and cardiomyocyte re-differentiation.
In Aim 2, we will investigate the therapeutic effects of agrin, whose administration into injured hearts of mice and pigs elicits a significant regenerative response. Specific objectives are matrix-related cardiac regenerative cues, modulation of the immune response, angiogenesis, matrix remodeling, and developing a preclinical, large animal model to study agrin efficacy for cardiac repair.
Interrogating the differences and similarities between our two regenerative models should give us a detailed roadmap for cardiac regenerative medicine by providing deeper knowledge of the regenerative process in the heart and pointing to novel targets for cardiac repair in human patients.
Max ERC Funding
2 268 750 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym CSG
Project C° symplectic geometry
Researcher (PI) Lev Buhovski
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Starting Grant (StG), PE1, ERC-2017-STG
Summary "The objective of this proposal is to study ""continuous"" (or C^0) objects, as well as C^0 properties of smooth objects, in the field of symplectic geometry and topology. C^0 symplectic geometry has seen spectacular progress in recent years, drawing attention of mathematicians from various background. The proposed study aims to discover new fascinating C^0 phenomena in symplectic geometry.
One circle of questions concerns symplectic and Hamiltonian homeomorphisms. Recent studies indicate that these objects possess both rigidity and flexibility, appearing in surprising and counter-intuitive ways. Our understanding of symplectic and Hamiltonian homeomorphisms is far from being satisfactory, and here we intend to study questions related to action of symplectic homeomorphisms on submanifolds. Some other questions are about Hamiltonian homeomorphisms in relation to the celebrated Arnold conjecture. The PI suggests to study spectral invariants of continuous Hamiltonian flows, which allow to formulate the C^0 Arnold conjecture in higher dimensions. Another central problem that the PI will work on is the C^0 flux conjecture.
A second circle of questions is about the Poisson bracket operator, and its functional-theoretic properties. The first question concerns the lower bound for the Poisson bracket invariant of a cover, conjectured by L. Polterovich who indicated relations between this problem and quantum mechanics. Another direction aims to study the C^0 rigidity versus flexibility of the L_p norm of the Poisson bracket. Despite a recent progress in dimension two showing rigidity, very little is known in higher dimensions. The PI proposes to use combination of tools from topology and from hard analysis in order to address this question, whose solution will be a big step towards understanding functional-theoretic properties of the Poisson bracket operator."
Summary
"The objective of this proposal is to study ""continuous"" (or C^0) objects, as well as C^0 properties of smooth objects, in the field of symplectic geometry and topology. C^0 symplectic geometry has seen spectacular progress in recent years, drawing attention of mathematicians from various background. The proposed study aims to discover new fascinating C^0 phenomena in symplectic geometry.
One circle of questions concerns symplectic and Hamiltonian homeomorphisms. Recent studies indicate that these objects possess both rigidity and flexibility, appearing in surprising and counter-intuitive ways. Our understanding of symplectic and Hamiltonian homeomorphisms is far from being satisfactory, and here we intend to study questions related to action of symplectic homeomorphisms on submanifolds. Some other questions are about Hamiltonian homeomorphisms in relation to the celebrated Arnold conjecture. The PI suggests to study spectral invariants of continuous Hamiltonian flows, which allow to formulate the C^0 Arnold conjecture in higher dimensions. Another central problem that the PI will work on is the C^0 flux conjecture.
A second circle of questions is about the Poisson bracket operator, and its functional-theoretic properties. The first question concerns the lower bound for the Poisson bracket invariant of a cover, conjectured by L. Polterovich who indicated relations between this problem and quantum mechanics. Another direction aims to study the C^0 rigidity versus flexibility of the L_p norm of the Poisson bracket. Despite a recent progress in dimension two showing rigidity, very little is known in higher dimensions. The PI proposes to use combination of tools from topology and from hard analysis in order to address this question, whose solution will be a big step towards understanding functional-theoretic properties of the Poisson bracket operator."
Max ERC Funding
1 345 282 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
