Project acronym 5HT-OPTOGENETICS
Project Optogenetic Analysis of Serotonin Function in the Mammalian Brain
Researcher (PI) Zachary Mainen
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.
Summary
Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.
Max ERC Funding
2 318 636 €
Duration
Start date: 2010-07-01, End date: 2015-12-31
Project acronym AFRICA-GHG
Project AFRICA-GHG: The role of African tropical forests on the Greenhouse Gases balance of the atmosphere
Researcher (PI) Riccardo Valentini
Host Institution (HI) FONDAZIONE CENTRO EURO-MEDITERRANEOSUI CAMBIAMENTI CLIMATICI
Call Details Advanced Grant (AdG), PE10, ERC-2009-AdG
Summary The role of the African continent in the global carbon cycle, and therefore in climate change, is increasingly recognised. Despite the increasingly acknowledged importance of Africa in the global carbon cycle and its high vulnerability to climate change there is still a lack of studies on the carbon cycle in representative African ecosystems (in particular tropical forests), and on the effects of climate on ecosystem-atmosphere exchange. In the present proposal we want to focus on these spoecifc objectives : 1. Understand the role of African tropical rainforest on the GHG balance of the atmosphere and revise their role on the global methane and N2O emissions. 2. Determine the carbon source/sink strength of African tropical rainforest in the pre-industrial versus the XXth century by temporal reconstruction of biomass growth with biogeochemical markers 3. Understand and quantify carbon and GHG fluxes variability across African tropical forests (west east equatorial belt) 4.Analyse the impact of forest degradation and deforestation on carbon and other GHG emissions
Summary
The role of the African continent in the global carbon cycle, and therefore in climate change, is increasingly recognised. Despite the increasingly acknowledged importance of Africa in the global carbon cycle and its high vulnerability to climate change there is still a lack of studies on the carbon cycle in representative African ecosystems (in particular tropical forests), and on the effects of climate on ecosystem-atmosphere exchange. In the present proposal we want to focus on these spoecifc objectives : 1. Understand the role of African tropical rainforest on the GHG balance of the atmosphere and revise their role on the global methane and N2O emissions. 2. Determine the carbon source/sink strength of African tropical rainforest in the pre-industrial versus the XXth century by temporal reconstruction of biomass growth with biogeochemical markers 3. Understand and quantify carbon and GHG fluxes variability across African tropical forests (west east equatorial belt) 4.Analyse the impact of forest degradation and deforestation on carbon and other GHG emissions
Max ERC Funding
2 406 950 €
Duration
Start date: 2010-04-01, End date: 2014-12-31
Project acronym CLEAR
Project Modulating cellular clearance to cure human disease
Researcher (PI) Andrea Ballabio
Host Institution (HI) FONDAZIONE TELETHON
Call Details Advanced Grant (AdG), LS2, ERC-2009-AdG
Summary Cellular clearance is a fundamental process required by all cells in all species. Important physiological processes, such as aging, and pathological mechanisms, such as neurodegeneration, are strictly dependent on cellular clearance. In eukaryotes, most of the cellular clearing processes occur in a specialized organelle, the lysosome. This project is based on a recent discovery, made in our laboratory, of a gene network, which we have named CLEAR, that controls lysosomal biogenesis and function and regulates cellular clearance. The specific goals of the project are: 1) the comprehensive characterization of the mechanisms underlying the CLEAR network, 2) the thorough understanding of CLEAR physiological function at the cellular and organism levels, 3) the development of strategies and tools to modulate cellular clearance, and 4) the implementation of proof-of-principle therapeutic studies based on the activation of the CLEAR network in murine models of human lysosomal storage disorders and of neurodegenerative diseases, such as Alzheimers s and Huntington s diseases. A combination of genomics, bioinformatics, systems biology, chemical genomics, cell biology, and mouse genetics approaches will be used to achieve these goals. Our goal is to develop tools to modulate cellular clearance and to use such tools to develop therapies to cure human disease. The potential medical relevance of this project is very high, particularly in the field of neurodegenerative disease. Therapies that prevent, ameliorate or delay neurodegeneration in these diseases would have a huge impact on human health.
Summary
Cellular clearance is a fundamental process required by all cells in all species. Important physiological processes, such as aging, and pathological mechanisms, such as neurodegeneration, are strictly dependent on cellular clearance. In eukaryotes, most of the cellular clearing processes occur in a specialized organelle, the lysosome. This project is based on a recent discovery, made in our laboratory, of a gene network, which we have named CLEAR, that controls lysosomal biogenesis and function and regulates cellular clearance. The specific goals of the project are: 1) the comprehensive characterization of the mechanisms underlying the CLEAR network, 2) the thorough understanding of CLEAR physiological function at the cellular and organism levels, 3) the development of strategies and tools to modulate cellular clearance, and 4) the implementation of proof-of-principle therapeutic studies based on the activation of the CLEAR network in murine models of human lysosomal storage disorders and of neurodegenerative diseases, such as Alzheimers s and Huntington s diseases. A combination of genomics, bioinformatics, systems biology, chemical genomics, cell biology, and mouse genetics approaches will be used to achieve these goals. Our goal is to develop tools to modulate cellular clearance and to use such tools to develop therapies to cure human disease. The potential medical relevance of this project is very high, particularly in the field of neurodegenerative disease. Therapies that prevent, ameliorate or delay neurodegeneration in these diseases would have a huge impact on human health.
Max ERC Funding
2 100 000 €
Duration
Start date: 2010-03-01, End date: 2015-02-28
Project acronym COGSYSTEMS
Project Understanding actions and intentions of others
Researcher (PI) Giacomo Rizzolatti
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PARMA
Call Details Advanced Grant (AdG), LS5, ERC-2009-AdG
Summary How do we understand the actions and intentions of others? Hereby we intend to address this issue by using a multidisciplinary approach. Our project is subdivided into four parts. In the first part we investigate the neural organization of monkey area F5, an area deeply involved in motor act understanding. By using a new set of electrodes we will describe the columnar organization of the area F5, establish the temporal relationships between the activity of F5 mirror and motor neurons, and correlate the activity of mirror neurons coding the observed motor acts in peripersonal and extrapersonal space with the activity of motor neurons in the same cortical column. In the second part we will assess the neural mechanism underlying the understanding of the intention of complex actions , i.e. actions formed by a sequence of two (or more) individual actions. The focus will be on the neurons located in ventrolateral prefrontal cortex, an area involved in the organization of high-order motor behavior. The rational of the experiment is that, while the organization of single actions and the understanding of intention behind them is function of parietal neurons, that of complex actions relies on the activity of the prefrontal lobe. In the third and fourth parts of the project we will delimit the cortical areas involved in understanding the goal (the what) and the intention (the why) of the observed actions in individuals with typical development (TD) and in children with autism and will establish the time relation between these two processes. Our hypothesis is that the chained organization of intentional motor acts is impaired in children with autism and this impairment prevents them from organizing normally their actions and from understanding others intentions.
Summary
How do we understand the actions and intentions of others? Hereby we intend to address this issue by using a multidisciplinary approach. Our project is subdivided into four parts. In the first part we investigate the neural organization of monkey area F5, an area deeply involved in motor act understanding. By using a new set of electrodes we will describe the columnar organization of the area F5, establish the temporal relationships between the activity of F5 mirror and motor neurons, and correlate the activity of mirror neurons coding the observed motor acts in peripersonal and extrapersonal space with the activity of motor neurons in the same cortical column. In the second part we will assess the neural mechanism underlying the understanding of the intention of complex actions , i.e. actions formed by a sequence of two (or more) individual actions. The focus will be on the neurons located in ventrolateral prefrontal cortex, an area involved in the organization of high-order motor behavior. The rational of the experiment is that, while the organization of single actions and the understanding of intention behind them is function of parietal neurons, that of complex actions relies on the activity of the prefrontal lobe. In the third and fourth parts of the project we will delimit the cortical areas involved in understanding the goal (the what) and the intention (the why) of the observed actions in individuals with typical development (TD) and in children with autism and will establish the time relation between these two processes. Our hypothesis is that the chained organization of intentional motor acts is impaired in children with autism and this impairment prevents them from organizing normally their actions and from understanding others intentions.
Max ERC Funding
1 992 000 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym COMBOS
Project Collective phenomena in quantum and classical many body systems
Researcher (PI) Alessandro Giuliani
Host Institution (HI) UNIVERSITA DEGLI STUDI ROMA TRE
Call Details Starting Grant (StG), PE1, ERC-2009-StG
Summary The collective behavior of quantum and classical many body systems such as ultracold atomic gases, nanowires, cuprates and micromagnets are currently subject of an intense experimental and theoretical research worldwide. Understanding the fascinating phenomena of Bose-Einstein condensation, Luttinger liquid vs non-Luttinger liquid behavior, high temperature superconductivity, and spontaneous formation of periodic patterns in magnetic systems, is an exciting challenge for theoreticians. Most of these phenomena are still far from being fully understood, even from a heuristic point of view. Unveiling the exotic properties of such systems by rigorous mathematical analysis is an important and difficult challenge for mathematical physics. In the last two decades, substantial progress has been made on various aspects of many-body theory, including Fermi liquids, Luttinger liquids, perturbed Ising models at criticality, bosonization, trapped Bose gases and spontaneous formation of periodic patterns. The techniques successfully employed in this field are diverse, and range from constructive renormalization group to functional variational estimates. In this research project we propose to investigate a number of statistical mechanics models by a combination of different mathematical methods. The objective is, on the one hand, to understand crossover phenomena, phase transitions and low-temperature states with broken symmetry, which are of interest in the theory of condensed matter and that we believe to be accessible to the currently available methods; on the other, to develop new techiques combining different and complementary methods, such as multiscale analysis and localization bounds, or reflection positivity and cluster expansion, which may be useful to further progress on important open problems, such as Bose-Einstein condensation, conformal invariance in non-integrable models, existence of magnetic or superconducting long range order.
Summary
The collective behavior of quantum and classical many body systems such as ultracold atomic gases, nanowires, cuprates and micromagnets are currently subject of an intense experimental and theoretical research worldwide. Understanding the fascinating phenomena of Bose-Einstein condensation, Luttinger liquid vs non-Luttinger liquid behavior, high temperature superconductivity, and spontaneous formation of periodic patterns in magnetic systems, is an exciting challenge for theoreticians. Most of these phenomena are still far from being fully understood, even from a heuristic point of view. Unveiling the exotic properties of such systems by rigorous mathematical analysis is an important and difficult challenge for mathematical physics. In the last two decades, substantial progress has been made on various aspects of many-body theory, including Fermi liquids, Luttinger liquids, perturbed Ising models at criticality, bosonization, trapped Bose gases and spontaneous formation of periodic patterns. The techniques successfully employed in this field are diverse, and range from constructive renormalization group to functional variational estimates. In this research project we propose to investigate a number of statistical mechanics models by a combination of different mathematical methods. The objective is, on the one hand, to understand crossover phenomena, phase transitions and low-temperature states with broken symmetry, which are of interest in the theory of condensed matter and that we believe to be accessible to the currently available methods; on the other, to develop new techiques combining different and complementary methods, such as multiscale analysis and localization bounds, or reflection positivity and cluster expansion, which may be useful to further progress on important open problems, such as Bose-Einstein condensation, conformal invariance in non-integrable models, existence of magnetic or superconducting long range order.
Max ERC Funding
650 000 €
Duration
Start date: 2010-01-01, End date: 2014-12-31
Project acronym CONLAWS
Project Hyperbolic Systems of Conservation Laws: singular limits, properties of solutions and control problems
Researcher (PI) Stefano Bianchini
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Call Details Starting Grant (StG), PE1, ERC-2009-StG
Summary The research program concerns various theoretic aspects of hyperbolic conservation laws. In first place we plan to study the existence and uniqueness of solutions to systems of equations of mathematical physics with physic viscosity. This is one of the main open problems within the theory of conservation laws in one space dimension, which cannot be tackled relying on the techniques developed in the case where the viscosity matrix is the identity. Furthermore, this represents a first step toward the analysis of more complex relaxation and kinetic models with a finite number of velocities as for Broadwell equation, or with a continuous distribution of velocities as for Boltzmann equation. A second research topic concerns the study of conservation laws with large data. Even in this case the basic model is provided by fluidodynamic equations. We wish to extend the results of existence, uniqueness and continuous dependence of solutions to the case of large (in BV or in L^infty) data, at least for the simplest systems of mathematical physics such as the isentropic gas dynamics. A third research topic that we wish to pursue concerns the analysis of fine properties of solutions to conservation laws. Many of such properties depend on the existence of one or more entropies of the system. In particular, we have in mind to study the regularity and the concentration of the dissipativity measure for an entropic solution of a system of conservation laws. Finally, we wish to continue the study of hyperbolic equations from the control theory point of view along two directions: (i) the analysis of controllability and asymptotic stabilizability properties; (ii) the study of optimal control problems related to hyperbolic systems.
Summary
The research program concerns various theoretic aspects of hyperbolic conservation laws. In first place we plan to study the existence and uniqueness of solutions to systems of equations of mathematical physics with physic viscosity. This is one of the main open problems within the theory of conservation laws in one space dimension, which cannot be tackled relying on the techniques developed in the case where the viscosity matrix is the identity. Furthermore, this represents a first step toward the analysis of more complex relaxation and kinetic models with a finite number of velocities as for Broadwell equation, or with a continuous distribution of velocities as for Boltzmann equation. A second research topic concerns the study of conservation laws with large data. Even in this case the basic model is provided by fluidodynamic equations. We wish to extend the results of existence, uniqueness and continuous dependence of solutions to the case of large (in BV or in L^infty) data, at least for the simplest systems of mathematical physics such as the isentropic gas dynamics. A third research topic that we wish to pursue concerns the analysis of fine properties of solutions to conservation laws. Many of such properties depend on the existence of one or more entropies of the system. In particular, we have in mind to study the regularity and the concentration of the dissipativity measure for an entropic solution of a system of conservation laws. Finally, we wish to continue the study of hyperbolic equations from the control theory point of view along two directions: (i) the analysis of controllability and asymptotic stabilizability properties; (ii) the study of optimal control problems related to hyperbolic systems.
Max ERC Funding
422 000 €
Duration
Start date: 2009-11-01, End date: 2013-10-31
Project acronym CRIPHERASY
Project Critical Phenomena in Random Systems
Researcher (PI) Giorgio Parisi
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Call Details Advanced Grant (AdG), PE2, ERC-2009-AdG
Summary This project aims to get a theoretical understanding of the most important large-scale phenomena in classical and quantum disordered systems. Thanks to the renormalization group approach the critical behaviour of pure systems is under very good control; however disordered systems are in many ways remarkably peculiar (think for example to non-perturbative phenomena like Griffiths singularities), often the conventional approach does not work and many crucial issues are still unclear. My work aims to fill this important hole in our understanding of disordered systems. I will concentrate my efforts on some of the most important and studied systems, i.e. spin glasses, random field ferromagnets (that are realized in nature as diluted antiferromagnets in a field), Anderson and Mott localization (with possible experimental applications to Bose-Einstein condensates and to electron glasses), surface growth in random media (KPZ and DLA models). In this project I want to pursue a new approach to these problems. I aim to compute in the most accurate way the properties of these systems using the original Wilson formulation of the renormalization group with a phase space cell analysis; this is equivalent to solving a statistical model on a hierarchical lattice (Dyson-Bleher-Sinai model). This is not an easy job. In the same conceptual frame we plan to use simultaneously very different techniques: probabilistic techniques, perturbative techniques at high orders, expansions around mean field on Bethe lattice and numerical techniques to evaluate the critical behaviour. I believe that even this restricted approach is very ambitious, but that the theoretical progresses that have been done in unveiling important features of disordered systems suggest that it will be possible to obtain solid results.
Summary
This project aims to get a theoretical understanding of the most important large-scale phenomena in classical and quantum disordered systems. Thanks to the renormalization group approach the critical behaviour of pure systems is under very good control; however disordered systems are in many ways remarkably peculiar (think for example to non-perturbative phenomena like Griffiths singularities), often the conventional approach does not work and many crucial issues are still unclear. My work aims to fill this important hole in our understanding of disordered systems. I will concentrate my efforts on some of the most important and studied systems, i.e. spin glasses, random field ferromagnets (that are realized in nature as diluted antiferromagnets in a field), Anderson and Mott localization (with possible experimental applications to Bose-Einstein condensates and to electron glasses), surface growth in random media (KPZ and DLA models). In this project I want to pursue a new approach to these problems. I aim to compute in the most accurate way the properties of these systems using the original Wilson formulation of the renormalization group with a phase space cell analysis; this is equivalent to solving a statistical model on a hierarchical lattice (Dyson-Bleher-Sinai model). This is not an easy job. In the same conceptual frame we plan to use simultaneously very different techniques: probabilistic techniques, perturbative techniques at high orders, expansions around mean field on Bethe lattice and numerical techniques to evaluate the critical behaviour. I believe that even this restricted approach is very ambitious, but that the theoretical progresses that have been done in unveiling important features of disordered systems suggest that it will be possible to obtain solid results.
Max ERC Funding
2 098 800 €
Duration
Start date: 2010-01-01, End date: 2014-12-31
Project acronym DISQUA
Project Disorder physics with ultracold quantum gases
Researcher (PI) Massimo Inguscio
Host Institution (HI) LABORATORIO EUROPEO DI SPETTROSCOPIE NON LINEARI
Call Details Advanced Grant (AdG), PE2, ERC-2009-AdG
Summary Disorder is ubiquitous in nature and has a strong impact on the behaviour of many physical systems. The most celebrated effect of disorder is Anderson localization of single particles, but many other more complex phenomena arise in interacting, many-body systems. A full understanding of how disorder affects the behavior of quantum systems is still missing, also because of the unavoidable presence of nonlinearities, dissipation and thermal effects that make a careful exploration of real condensed-matter systems very difficult. In this project we want to fully exploit the unprecedented potentialities offered by ultracold atomic quantum gases to explore some of the present challenges for our understanding of the physics of disorder. These systems offer indeed the possibility of controlling to a great extent crucial parameters such as the type of disorder, the nonlinearities due to interactions, the temperature and density, the dimensionality, the quantum statistics. A variety of advanced diagnostic techniques allow to gain detailed information on the static and dynamic properties of the system. The potentialities of atomic quantum gases for the study of disorder have already showed up in recent breakthrough experiments. The project aims at an experimental exploration, supported by advanced theory, of the current issues in disordered quantum systems. We will investigate a few frontier themes of general interest: 1) Anderson localization and the interplay of disorder and a weak interaction; 2) strongly correlated, disordered bosonic systems; 3) disordered, interacting fermionic systems. In the research we will employ atomic Bose and Fermi gases with tunable interactions and advanced diagnostic techniques that we have recently contributed to develop. A successful completion of the project will push forward our understanding of the behaviour of quantum systems with disorder, with a potentially large impact on many fields of physics.
Summary
Disorder is ubiquitous in nature and has a strong impact on the behaviour of many physical systems. The most celebrated effect of disorder is Anderson localization of single particles, but many other more complex phenomena arise in interacting, many-body systems. A full understanding of how disorder affects the behavior of quantum systems is still missing, also because of the unavoidable presence of nonlinearities, dissipation and thermal effects that make a careful exploration of real condensed-matter systems very difficult. In this project we want to fully exploit the unprecedented potentialities offered by ultracold atomic quantum gases to explore some of the present challenges for our understanding of the physics of disorder. These systems offer indeed the possibility of controlling to a great extent crucial parameters such as the type of disorder, the nonlinearities due to interactions, the temperature and density, the dimensionality, the quantum statistics. A variety of advanced diagnostic techniques allow to gain detailed information on the static and dynamic properties of the system. The potentialities of atomic quantum gases for the study of disorder have already showed up in recent breakthrough experiments. The project aims at an experimental exploration, supported by advanced theory, of the current issues in disordered quantum systems. We will investigate a few frontier themes of general interest: 1) Anderson localization and the interplay of disorder and a weak interaction; 2) strongly correlated, disordered bosonic systems; 3) disordered, interacting fermionic systems. In the research we will employ atomic Bose and Fermi gases with tunable interactions and advanced diagnostic techniques that we have recently contributed to develop. A successful completion of the project will push forward our understanding of the behaviour of quantum systems with disorder, with a potentially large impact on many fields of physics.
Max ERC Funding
2 500 000 €
Duration
Start date: 2010-03-01, End date: 2015-02-28
Project acronym DYCOCA
Project DYNAMIC COVALENT CAPTURE: Dynamic Chemistry for Biomolecular Recognition and Catalysis
Researcher (PI) Leonard Jan Prins
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Call Details Starting Grant (StG), PE5, ERC-2009-StG
Summary Molecular recognition plays a fundamental role in nearly all chemical and biological processes. The objective of this research project is to develop new methodology for studying and utilizing the noncovalent recognition between two molecular entities, focussing on biomolecular receptors and catalysts. A dynamic covalent capture strategy is proposed, characterized by the following strongholds. The target itself self-selects the best component out of a combinatorial library. The approach has a very high sensitivity, because molecular recognition occurs intramolecularly, and is very flexible, which allows for an easy implementation in very diverse research areas simply by changing the target. The dynamic covalent capture strategy is strongly embedded in the fields of supramolecular chemistry and (physical) organic chemistry. Nonetheless, the different work programmes strongly rely on the input from other areas, such as combinatorial chemistry, bioorganic chemistry, catalysis and computational chemistry, which renders the project highly interdisciplinary. Identified targets are new synthetic catalysts for the selective cleavage of biologically relevant compounds (D-Ala-D-Lac, cocaine and acetylcholine, and in a later stage peptides and DNA/RNA). Applicative work programmes are dedicated to the dynamic imprinting of monolayers on nanoparticles for multivalent recognition and cleavage of biologically relevant targets in vivo and to the development of new screening methodology for measuring chemical equilibria and, specifically, for the discovery of new HIV-1 fusion inhibitors.
Summary
Molecular recognition plays a fundamental role in nearly all chemical and biological processes. The objective of this research project is to develop new methodology for studying and utilizing the noncovalent recognition between two molecular entities, focussing on biomolecular receptors and catalysts. A dynamic covalent capture strategy is proposed, characterized by the following strongholds. The target itself self-selects the best component out of a combinatorial library. The approach has a very high sensitivity, because molecular recognition occurs intramolecularly, and is very flexible, which allows for an easy implementation in very diverse research areas simply by changing the target. The dynamic covalent capture strategy is strongly embedded in the fields of supramolecular chemistry and (physical) organic chemistry. Nonetheless, the different work programmes strongly rely on the input from other areas, such as combinatorial chemistry, bioorganic chemistry, catalysis and computational chemistry, which renders the project highly interdisciplinary. Identified targets are new synthetic catalysts for the selective cleavage of biologically relevant compounds (D-Ala-D-Lac, cocaine and acetylcholine, and in a later stage peptides and DNA/RNA). Applicative work programmes are dedicated to the dynamic imprinting of monolayers on nanoparticles for multivalent recognition and cleavage of biologically relevant targets in vivo and to the development of new screening methodology for measuring chemical equilibria and, specifically, for the discovery of new HIV-1 fusion inhibitors.
Max ERC Funding
1 400 000 €
Duration
Start date: 2009-10-01, End date: 2014-09-30
Project acronym EBLA CHORA
Project The early state and its chora. Towns, villages and landscape at Ebla in Syria during the 3rd Millennium BC. Royal archives, visual and material culture, remote sensing and artificial neural networks
Researcher (PI) Paolo Matthiae
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Call Details Advanced Grant (AdG), SH6, ERC-2009-AdG
Summary The case of Ebla in northern Syria is certainly the most favourable one for enhancing our understanding of mechanisms of functioning of the early state. The discovery in 1975 of royal archives consisting of 17.000 cuneiform tablets dating to c. 2300 BC has supplied the scientific community with an invaluable mass of documents dealing with all aspects of state organization. These tablets inform us about the political, diplomatic and military affairs of the Eblaite state, as well as on the economic and social fabric of this early state formation. Further, considerable progresses during the past decade have been made at Ebla in seriating material culture assemblages, in interpreting the rich evidence for ancient visual communication and in exposing the urban structure. We now foresee a unique opportunity to test theories and models about the rise and structure of the early state by expanding the level of analysis to the landscape around Ebla: archaeological surface surveys, remote sensing, geomorphological studies will be evaluated together with the results of archaeological and geophysic investigations on village sites. Our research group has already considerable experience in developing calculation programs that employ along with traditional statistic and quantitative methods within a web GIS environment, including all the cuneiform tablets models of modern dynamic mathematics: the massive amount of data obtained from excavations, surveys, epigraphic studies, archeometric and archeobiological analyses will be combined and analyzed by means of mathematical, economical and computer science concepts and models, in order to build a multi-tier explanatory pattern which can be applied also to other early foci of urbanization in the Near East and elsewhere. We thus hope to gain a much richer historical framework and a sophisticated predictive model of general validity: until now no studies have ever focused on explanations of these phenomena on such an integrated scale
Summary
The case of Ebla in northern Syria is certainly the most favourable one for enhancing our understanding of mechanisms of functioning of the early state. The discovery in 1975 of royal archives consisting of 17.000 cuneiform tablets dating to c. 2300 BC has supplied the scientific community with an invaluable mass of documents dealing with all aspects of state organization. These tablets inform us about the political, diplomatic and military affairs of the Eblaite state, as well as on the economic and social fabric of this early state formation. Further, considerable progresses during the past decade have been made at Ebla in seriating material culture assemblages, in interpreting the rich evidence for ancient visual communication and in exposing the urban structure. We now foresee a unique opportunity to test theories and models about the rise and structure of the early state by expanding the level of analysis to the landscape around Ebla: archaeological surface surveys, remote sensing, geomorphological studies will be evaluated together with the results of archaeological and geophysic investigations on village sites. Our research group has already considerable experience in developing calculation programs that employ along with traditional statistic and quantitative methods within a web GIS environment, including all the cuneiform tablets models of modern dynamic mathematics: the massive amount of data obtained from excavations, surveys, epigraphic studies, archeometric and archeobiological analyses will be combined and analyzed by means of mathematical, economical and computer science concepts and models, in order to build a multi-tier explanatory pattern which can be applied also to other early foci of urbanization in the Near East and elsewhere. We thus hope to gain a much richer historical framework and a sophisticated predictive model of general validity: until now no studies have ever focused on explanations of these phenomena on such an integrated scale
Max ERC Funding
1 105 240 €
Duration
Start date: 2010-04-01, End date: 2014-03-31
