Project acronym B2C
Project Beasts to Craft: BioCodicology as a new approach to the study of parchment manuscripts
Researcher (PI) Matthew COLLINS
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Advanced Grant (AdG), SH6, ERC-2017-ADG
Summary The intention of Beasts to Craft (B2C) is to document the biological and craft records in parchment in order to reveal the entangled histories of animal improvement and parchment production in Europe from 500-1900 AD.
B2C will lay the foundations for a new approach to the the study of parchment manuscripts —biocodicology— which draws evidence from the overlooked first stages in production, the raising of livestock and the preparation of the skins.
1. Parchment is an extraordinary but overlooked high resolution zooarchaeological record and a molecular archive. Livestock genetics is revealing breed diversity and markers of character traits such as fleece quality. B2C will exploit this new-found knowledge, using progressively older dated archival (sheep) parchments to study the history of improvement 1300 - 1900. Visual examination of the skins will search for direct evidence of disease and fleece quality.
2. Craft skills can be read from parchment and, when combined with chemical data and comparison with modern analogues, will produce the first European wide record of the craft from 500-1900. The size and scope of this the parchment archive means it is one of the largest and most highly resolved records of a specialist medieval craft. We will explore how these skills develop and when and where regional patterns appear and decline.
These two remarkable records requires a large interdisciplinary team. However biocodicology draws from and informs upon a wide and diverse spectrum of existing scholarship in conservation, the arts and sciences. A third strand of the project will (i) furnish manuscript scholars with some of the information available to the scribe at time of production (ii) inform and shape attitudes to parchment conservation (iii) provide high resolution biological data on animal management, movement and health and (iv) explore methods to link datasets and promote data reuse.
Summary
The intention of Beasts to Craft (B2C) is to document the biological and craft records in parchment in order to reveal the entangled histories of animal improvement and parchment production in Europe from 500-1900 AD.
B2C will lay the foundations for a new approach to the the study of parchment manuscripts —biocodicology— which draws evidence from the overlooked first stages in production, the raising of livestock and the preparation of the skins.
1. Parchment is an extraordinary but overlooked high resolution zooarchaeological record and a molecular archive. Livestock genetics is revealing breed diversity and markers of character traits such as fleece quality. B2C will exploit this new-found knowledge, using progressively older dated archival (sheep) parchments to study the history of improvement 1300 - 1900. Visual examination of the skins will search for direct evidence of disease and fleece quality.
2. Craft skills can be read from parchment and, when combined with chemical data and comparison with modern analogues, will produce the first European wide record of the craft from 500-1900. The size and scope of this the parchment archive means it is one of the largest and most highly resolved records of a specialist medieval craft. We will explore how these skills develop and when and where regional patterns appear and decline.
These two remarkable records requires a large interdisciplinary team. However biocodicology draws from and informs upon a wide and diverse spectrum of existing scholarship in conservation, the arts and sciences. A third strand of the project will (i) furnish manuscript scholars with some of the information available to the scribe at time of production (ii) inform and shape attitudes to parchment conservation (iii) provide high resolution biological data on animal management, movement and health and (iv) explore methods to link datasets and promote data reuse.
Max ERC Funding
2 499 462 €
Duration
Start date: 2018-12-01, End date: 2023-11-30
Project acronym BRAINCANNABINOIDS
Project Understanding the molecular blueprint and functional complexity of the endocannabinoid metabolome in the brain
Researcher (PI) István Katona
Host Institution (HI) INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES
Call Details Starting Grant (StG), LS5, ERC-2009-StG
Summary We and others have recently delineated the molecular architecture of a new feedback pathway in brain synapses, which operates as a synaptic circuit breaker. This pathway is supposed to use a group of lipid messengers as retrograde synaptic signals, the so-called endocannabinoids. Although heterogeneous in their chemical structures, these molecules along with the psychoactive compound in cannabis are thought to target the same effector in the brain, the CB1 receptor. However, the molecular catalog of these bioactive lipids and their metabolic enzymes has been expanding rapidly by recent advances in lipidomics and proteomics raising the possibility that these lipids may also serve novel, yet unidentified physiological functions. Thus, the overall aim of our research program is to define the molecular and anatomical organization of these endocannabinoid-mediated pathways and to determine their functional significance. In the present proposal, we will focus on understanding how these novel pathways regulate synaptic and extrasynaptic signaling in hippocampal neurons. Using combination of lipidomic, genetic and high-resolution anatomical approaches, we will identify distinct chemical species of endocannabinoids and will show how their metabolic enzymes are segregated into different subcellular compartments in cell type- and synapse-specific manner. Subsequently, we will use genetically encoded gain-of-function, loss-of-function and reporter constructs in imaging experiments and electrophysiological recordings to gain insights into the diverse tasks that these new pathways serve in synaptic transmission and extrasynaptic signal processing. Our proposed experiments will reveal fundamental principles of intercellular and intracellular endocannabinoid signaling in the brain.
Summary
We and others have recently delineated the molecular architecture of a new feedback pathway in brain synapses, which operates as a synaptic circuit breaker. This pathway is supposed to use a group of lipid messengers as retrograde synaptic signals, the so-called endocannabinoids. Although heterogeneous in their chemical structures, these molecules along with the psychoactive compound in cannabis are thought to target the same effector in the brain, the CB1 receptor. However, the molecular catalog of these bioactive lipids and their metabolic enzymes has been expanding rapidly by recent advances in lipidomics and proteomics raising the possibility that these lipids may also serve novel, yet unidentified physiological functions. Thus, the overall aim of our research program is to define the molecular and anatomical organization of these endocannabinoid-mediated pathways and to determine their functional significance. In the present proposal, we will focus on understanding how these novel pathways regulate synaptic and extrasynaptic signaling in hippocampal neurons. Using combination of lipidomic, genetic and high-resolution anatomical approaches, we will identify distinct chemical species of endocannabinoids and will show how their metabolic enzymes are segregated into different subcellular compartments in cell type- and synapse-specific manner. Subsequently, we will use genetically encoded gain-of-function, loss-of-function and reporter constructs in imaging experiments and electrophysiological recordings to gain insights into the diverse tasks that these new pathways serve in synaptic transmission and extrasynaptic signal processing. Our proposed experiments will reveal fundamental principles of intercellular and intracellular endocannabinoid signaling in the brain.
Max ERC Funding
1 638 000 €
Duration
Start date: 2009-11-01, End date: 2014-10-31
Project acronym BTVI
Project First Biodegradable Biocatalytic VascularTherapeutic Implants
Researcher (PI) Alexander Zelikin
Host Institution (HI) AARHUS UNIVERSITET
Call Details Consolidator Grant (CoG), PE8, ERC-2013-CoG
Summary "We aim to perform academic development of a novel biomedical opportunity: localized synthesis of drugs within biocatalytic therapeutic vascular implants (BVI) for site-specific drug delivery to target organs and tissues. Primary envisioned targets for therapeutic intervention using BVI are atherosclerosis, viral hepatitis, and hepatocellular carcinoma: three of the most prevalent and debilitating conditions which affect hundreds of millions worldwide and which continue to increase in their importance in the era of increasingly aging population. For hepatic applications, we aim to develop drug eluting beads which are equipped with tools of enzyme-prodrug therapy (EPT) and are administered to the liver via trans-arterial catheter embolization. Therein, the beads perform localized synthesis of drugs and imaging reagents for anticancer combination therapy and theranostics, antiviral and anti-inflammatory agents for the treatment of hepatitis. Further, we conceive vascular therapeutic inserts (VTI) as a novel type of implantable biomaterials for treatment of atherosclerosis and re-endothelialization of vascular stents and grafts. Using EPT, inserts will tame “the guardian of cardiovascular grafts”, nitric oxide, for which localized, site specific synthesis and delivery spell success of therapeutic intervention and/or aided tissue regeneration. This proposal is positioned on the forefront of biomedical engineering and its success requires excellence in polymer chemistry, materials design, medicinal chemistry, and translational medicine. Each part of this proposal - design of novel types of vascular implants, engineering novel biomaterials, developing innovative fabrication and characterization techniques – is of high value for fundamental biomedical sciences. The project is target-oriented and once successful, will be of highest practical value and contribute to increased quality of life of millions of people worldwide."
Summary
"We aim to perform academic development of a novel biomedical opportunity: localized synthesis of drugs within biocatalytic therapeutic vascular implants (BVI) for site-specific drug delivery to target organs and tissues. Primary envisioned targets for therapeutic intervention using BVI are atherosclerosis, viral hepatitis, and hepatocellular carcinoma: three of the most prevalent and debilitating conditions which affect hundreds of millions worldwide and which continue to increase in their importance in the era of increasingly aging population. For hepatic applications, we aim to develop drug eluting beads which are equipped with tools of enzyme-prodrug therapy (EPT) and are administered to the liver via trans-arterial catheter embolization. Therein, the beads perform localized synthesis of drugs and imaging reagents for anticancer combination therapy and theranostics, antiviral and anti-inflammatory agents for the treatment of hepatitis. Further, we conceive vascular therapeutic inserts (VTI) as a novel type of implantable biomaterials for treatment of atherosclerosis and re-endothelialization of vascular stents and grafts. Using EPT, inserts will tame “the guardian of cardiovascular grafts”, nitric oxide, for which localized, site specific synthesis and delivery spell success of therapeutic intervention and/or aided tissue regeneration. This proposal is positioned on the forefront of biomedical engineering and its success requires excellence in polymer chemistry, materials design, medicinal chemistry, and translational medicine. Each part of this proposal - design of novel types of vascular implants, engineering novel biomaterials, developing innovative fabrication and characterization techniques – is of high value for fundamental biomedical sciences. The project is target-oriented and once successful, will be of highest practical value and contribute to increased quality of life of millions of people worldwide."
Max ERC Funding
1 996 126 €
Duration
Start date: 2014-04-01, End date: 2019-09-30
Project acronym CASINO
Project Carbohydrate signals controlling nodulation
Researcher (PI) Jens Stougaard Jensen
Host Institution (HI) AARHUS UNIVERSITET
Call Details Advanced Grant (AdG), LS3, ERC-2010-AdG_20100317
Summary Mechanisms governing interaction between multicellular organisms and microbes are central for understanding pathogenesis, symbiosis and the function of ecosystems. We propose to address these mechanisms by pioneering an interdisciplinary approach for understanding cellular signalling, response processes and organ development. The challenge is to determine factors synchronising three processes, organogenesis, infection thread formation and bacterial infection, running in parallel to build a root nodule hosting symbiotic bacteria. We aim to exploit the unique possibilities for analysing endocytosis of bacteria in model legumes and to develop genomic, genetic and biological chemistry tools to break new ground in our understanding of carbohydrates in plant development and plant-microbe interaction. Surface exposed rhizobial polysaccharides play a crucial but poorly understood role in infection thread formation and rhizobial invasion resulting in endocytosis. We will undertake an integrated functional characterisation of receptor-ligand mechanisms mediating recognition of secreted polysaccharides and subsequent signal amplification. So far progress in this field has been limited by the complex nature of carbohydrate polymers, lack of a suitable experimental model system where both partners in an interaction could be manipulated and lack of corresponding methods for carbohydrate synthesis, analysis and interaction studies. In this context our legume model system and the discovery that the legume Nod-factor receptors recognise bacterial lipochitin-oligosaccharide signals at their LysM domains provides a new opportunity. Combined with advanced bioorganic chemistry and nanobioscience approaches this proposal will engage the above mentioned limitations.
Summary
Mechanisms governing interaction between multicellular organisms and microbes are central for understanding pathogenesis, symbiosis and the function of ecosystems. We propose to address these mechanisms by pioneering an interdisciplinary approach for understanding cellular signalling, response processes and organ development. The challenge is to determine factors synchronising three processes, organogenesis, infection thread formation and bacterial infection, running in parallel to build a root nodule hosting symbiotic bacteria. We aim to exploit the unique possibilities for analysing endocytosis of bacteria in model legumes and to develop genomic, genetic and biological chemistry tools to break new ground in our understanding of carbohydrates in plant development and plant-microbe interaction. Surface exposed rhizobial polysaccharides play a crucial but poorly understood role in infection thread formation and rhizobial invasion resulting in endocytosis. We will undertake an integrated functional characterisation of receptor-ligand mechanisms mediating recognition of secreted polysaccharides and subsequent signal amplification. So far progress in this field has been limited by the complex nature of carbohydrate polymers, lack of a suitable experimental model system where both partners in an interaction could be manipulated and lack of corresponding methods for carbohydrate synthesis, analysis and interaction studies. In this context our legume model system and the discovery that the legume Nod-factor receptors recognise bacterial lipochitin-oligosaccharide signals at their LysM domains provides a new opportunity. Combined with advanced bioorganic chemistry and nanobioscience approaches this proposal will engage the above mentioned limitations.
Max ERC Funding
2 399 127 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
Project acronym CholAminCo
Project Synergy and antagonism of cholinergic and dopaminergic systems in associative learning
Researcher (PI) Balazs Gyoergy HANGYA
Host Institution (HI) INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES
Call Details Starting Grant (StG), LS5, ERC-2016-STG
Summary Neuromodulators such as acetylcholine and dopamine are able to rapidly reprogram neuronal information processing and dynamically change brain states. Degeneration or dysfunction of cholinergic and dopaminergic neurons can lead to neuropsychiatric conditions like schizophrenia and addiction or cognitive diseases such as Alzheimer’s. Neuromodulatory systems control overlapping cognitive processes and often have similar modes of action; therefore it is important to reveal cooperation and competition between different systems to understand their unique contributions to cognitive functions like learning, memory and attention. This is only possible by direct comparison, which necessitates monitoring multiple neuromodulatory systems under identical experimental conditions. Moreover, simultaneous recording of different neuromodulatory cell types goes beyond phenomenological description of similarities and differences by revealing the underlying correlation structure at the level of action potential timing. However, such data allowing direct comparison of neuromodulatory actions are still sparse. As a first step to bridge this gap, I propose to elucidate the unique versus complementary roles of two “classical” neuromodulatory systems, the cholinergic and dopaminergic projection system implicated in various cognitive functions including associative learning and plasticity. First, we will record optogenetically identified cholinergic and dopaminergic neurons simultaneously using chronic extracellular recording in mice undergoing classical and operant conditioning. Second, we will determine the postsynaptic impact of cholinergic and dopaminergic neurons by manipulating them both separately and simultaneously while recording consequential changes in cortical neuronal activity and learning behaviour. These experiments will reveal how major neuromodulatory systems interact to mediate similar or different aspects of the same cognitive functions.
Summary
Neuromodulators such as acetylcholine and dopamine are able to rapidly reprogram neuronal information processing and dynamically change brain states. Degeneration or dysfunction of cholinergic and dopaminergic neurons can lead to neuropsychiatric conditions like schizophrenia and addiction or cognitive diseases such as Alzheimer’s. Neuromodulatory systems control overlapping cognitive processes and often have similar modes of action; therefore it is important to reveal cooperation and competition between different systems to understand their unique contributions to cognitive functions like learning, memory and attention. This is only possible by direct comparison, which necessitates monitoring multiple neuromodulatory systems under identical experimental conditions. Moreover, simultaneous recording of different neuromodulatory cell types goes beyond phenomenological description of similarities and differences by revealing the underlying correlation structure at the level of action potential timing. However, such data allowing direct comparison of neuromodulatory actions are still sparse. As a first step to bridge this gap, I propose to elucidate the unique versus complementary roles of two “classical” neuromodulatory systems, the cholinergic and dopaminergic projection system implicated in various cognitive functions including associative learning and plasticity. First, we will record optogenetically identified cholinergic and dopaminergic neurons simultaneously using chronic extracellular recording in mice undergoing classical and operant conditioning. Second, we will determine the postsynaptic impact of cholinergic and dopaminergic neurons by manipulating them both separately and simultaneously while recording consequential changes in cortical neuronal activity and learning behaviour. These experiments will reveal how major neuromodulatory systems interact to mediate similar or different aspects of the same cognitive functions.
Max ERC Funding
1 499 463 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym CIRCUITASSEMBLY
Project Development of functional organization of the visual circuits in mice
Researcher (PI) Keisuke Yonehara
Host Institution (HI) AARHUS UNIVERSITET
Call Details Starting Grant (StG), LS5, ERC-2014-STG
Summary The key organizing principles that characterize neuronal systems include asymmetric, parallel, and topographic connectivity of the neural circuits. The main aim of my research is to elucidate the key principles underlying functional development of neural circuits by focusing on those organizing principles. I choose mouse visual system as my model since it contains all of these principles and provides sophisticated genetic tools to label and manipulate individual circuit components. My research is based on the central hypothesis that the mechanisms of brain development cannot be fully understood without first identifying individual functional cell types in adults, and then understanding how the functions of these cell types become established, using cell-type-specific molecular and synaptic mechanisms in developing animals. Recently, I have identified several transgenic mouse lines in which specific cell types in a visual center, the superior colliculus, are labeled with Cre recombinase in both developing and adult animals. Here I will take advantage of these mouse lines to ask fundamental questions about the functional development of neural circuits. First, how are distinct sensory features processed by the parallel topographic neuronal pathways, and how do they contribute to behavior? Second, what are the molecular and synaptic mechanisms that underlie developmental circuit plasticity for forming parallel topographic neuronal maps in the brain? Third, what are the molecular mechanisms that set up spatially asymmetric circuit connectivity without the need for sensory experience? I predict that my insights into the developmental mechanism of asymmetric, parallel, and topographic connectivity and circuit plasticity will be instructive when studying other brain circuits which contain similar organizing principles.
Summary
The key organizing principles that characterize neuronal systems include asymmetric, parallel, and topographic connectivity of the neural circuits. The main aim of my research is to elucidate the key principles underlying functional development of neural circuits by focusing on those organizing principles. I choose mouse visual system as my model since it contains all of these principles and provides sophisticated genetic tools to label and manipulate individual circuit components. My research is based on the central hypothesis that the mechanisms of brain development cannot be fully understood without first identifying individual functional cell types in adults, and then understanding how the functions of these cell types become established, using cell-type-specific molecular and synaptic mechanisms in developing animals. Recently, I have identified several transgenic mouse lines in which specific cell types in a visual center, the superior colliculus, are labeled with Cre recombinase in both developing and adult animals. Here I will take advantage of these mouse lines to ask fundamental questions about the functional development of neural circuits. First, how are distinct sensory features processed by the parallel topographic neuronal pathways, and how do they contribute to behavior? Second, what are the molecular and synaptic mechanisms that underlie developmental circuit plasticity for forming parallel topographic neuronal maps in the brain? Third, what are the molecular mechanisms that set up spatially asymmetric circuit connectivity without the need for sensory experience? I predict that my insights into the developmental mechanism of asymmetric, parallel, and topographic connectivity and circuit plasticity will be instructive when studying other brain circuits which contain similar organizing principles.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-04-01, End date: 2020-03-31
Project acronym CLIOARCH
Project Cliodynamic archaeology: Computational approaches to Final Palaeolithic/earliest Mesolithic archaeology and climate change
Researcher (PI) Felix RIEDE
Host Institution (HI) AARHUS UNIVERSITET
Call Details Consolidator Grant (CoG), SH6, ERC-2018-COG
Summary Late Pleistocene/early Holocene Europe is said to be the ideal laboratory for the investigation of human responses to rapidly changing climates and environments, migration and adaptation. Yet, pinpointing precisely how and why contemporaneous Final Palaeolithic/earliest Mesolithic (15,000-11,000 years BP) foragers migrated, and which environmental or other factors they adapted to – or failed to – has remained remarkably elusive. At the core of ClioArch is the radical but, in light of research-historical insights, necessary hypothesis that the current archaeological cultural taxonomy for this iconic period of European prehistory is epistemologically flawed and that operationalisations and interpretations based on this traditional taxonomy – especially those that seek to relate observed changes in material culture and land-use to contemporaneous climatic and environmental changes – are therefore problematic. Hence, novel approaches to crafting the taxonomic building blocks are required, as are novel analyses of human|environment relations in this period. ClioArch’s premier ambition is to provide operational cultural taxonomies for the Final Palaeolithic/earliest Mesolithic of Europe and to couple these with interdisciplinary cultural evolutionary, quantitative ecological methods and field archaeological investigations beyond the state-of-the-art, so as to better capture such adaptations – almost certainly with major implications for the standard culture-historical narrative relating to this period. In so doing, the project will pioneer a fully transparent and replicable – and eminently transferable – methodology for the study of the impacts of climate change and extreme environmental events in deep history. In turn, such a quantitative understanding of past adaptive dynamics will position archaeology more centrally in contemporary debates about climate change, environmental catastrophe and their cultural dimensions.
Summary
Late Pleistocene/early Holocene Europe is said to be the ideal laboratory for the investigation of human responses to rapidly changing climates and environments, migration and adaptation. Yet, pinpointing precisely how and why contemporaneous Final Palaeolithic/earliest Mesolithic (15,000-11,000 years BP) foragers migrated, and which environmental or other factors they adapted to – or failed to – has remained remarkably elusive. At the core of ClioArch is the radical but, in light of research-historical insights, necessary hypothesis that the current archaeological cultural taxonomy for this iconic period of European prehistory is epistemologically flawed and that operationalisations and interpretations based on this traditional taxonomy – especially those that seek to relate observed changes in material culture and land-use to contemporaneous climatic and environmental changes – are therefore problematic. Hence, novel approaches to crafting the taxonomic building blocks are required, as are novel analyses of human|environment relations in this period. ClioArch’s premier ambition is to provide operational cultural taxonomies for the Final Palaeolithic/earliest Mesolithic of Europe and to couple these with interdisciplinary cultural evolutionary, quantitative ecological methods and field archaeological investigations beyond the state-of-the-art, so as to better capture such adaptations – almost certainly with major implications for the standard culture-historical narrative relating to this period. In so doing, the project will pioneer a fully transparent and replicable – and eminently transferable – methodology for the study of the impacts of climate change and extreme environmental events in deep history. In turn, such a quantitative understanding of past adaptive dynamics will position archaeology more centrally in contemporary debates about climate change, environmental catastrophe and their cultural dimensions.
Max ERC Funding
1 907 638 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym DeCode
Project Dendrites and memory: role of dendritic spikes in information coding by hippocampal CA3 pyramidal neurons
Researcher (PI) Judit MAKARA
Host Institution (HI) INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES
Call Details Consolidator Grant (CoG), LS5, ERC-2017-COG
Summary The hippocampus is essential for building episodic memories. Coding of locations, contexts or events in the hippocampus is based on the correlated activity of neuronal ensembles; however, the mechanisms promoting the recruitment of individual neurons into information-coding ensembles are poorly understood.
In particular, the recurrent synaptic network of pyramidal cells (PCs) in the hippocampal CA3 area, receiving external inputs from the entorhinal cortex and the dentate gyrus, is thought to be essential for associative memory. Current models of the associative functions of CA3 are mainly based on plasticity of these synaptic connections. Recent work by us and others however suggests that active, voltage-dependent properties of CA3PC dendrites may also promote ensemble functions. Dendritic voltage-dependent ion channels allow nonlinear amplification of spatiotemporally correlated synaptic inputs (such as those produced by ensemble activity) and can even generate local dendritic spikes, which may elicit specific action potential patterns and induce synaptic plasticity. Furthermore, dendritic processing may be modulated by activity-dependent regulation of dendritic ion channels. However, still little is known about the active properties of CA3PC dendrites and their functions during spatial coding or memory tasks.
The general aim of my research program is to understand the cellular mechanisms that underlie the formation of hippocampal memory-coding neuronal ensembles. Specifically, we will test the hypothesis that active input integration by dendrites of individual CA3PCs plays an important role in their recruitment into specific context-coding ensembles. By combining in vitro (patch-clamp electrophysiology and two-photon (2P) microscopy in slices) and in vivo (2P imaging and activity-dependent labelling in behaving rodents) approaches, we will provide an in-depth understanding of the dendritic components contributing to the generation of the CA3 ensemble code.
Summary
The hippocampus is essential for building episodic memories. Coding of locations, contexts or events in the hippocampus is based on the correlated activity of neuronal ensembles; however, the mechanisms promoting the recruitment of individual neurons into information-coding ensembles are poorly understood.
In particular, the recurrent synaptic network of pyramidal cells (PCs) in the hippocampal CA3 area, receiving external inputs from the entorhinal cortex and the dentate gyrus, is thought to be essential for associative memory. Current models of the associative functions of CA3 are mainly based on plasticity of these synaptic connections. Recent work by us and others however suggests that active, voltage-dependent properties of CA3PC dendrites may also promote ensemble functions. Dendritic voltage-dependent ion channels allow nonlinear amplification of spatiotemporally correlated synaptic inputs (such as those produced by ensemble activity) and can even generate local dendritic spikes, which may elicit specific action potential patterns and induce synaptic plasticity. Furthermore, dendritic processing may be modulated by activity-dependent regulation of dendritic ion channels. However, still little is known about the active properties of CA3PC dendrites and their functions during spatial coding or memory tasks.
The general aim of my research program is to understand the cellular mechanisms that underlie the formation of hippocampal memory-coding neuronal ensembles. Specifically, we will test the hypothesis that active input integration by dendrites of individual CA3PCs plays an important role in their recruitment into specific context-coding ensembles. By combining in vitro (patch-clamp electrophysiology and two-photon (2P) microscopy in slices) and in vivo (2P imaging and activity-dependent labelling in behaving rodents) approaches, we will provide an in-depth understanding of the dendritic components contributing to the generation of the CA3 ensemble code.
Max ERC Funding
1 990 314 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
Project acronym EIMS
Project "Early infectious, inflammatory and immune mechanisms in schizophrenia"
Researcher (PI) Preben Bo Mortensen
Host Institution (HI) AARHUS UNIVERSITET
Call Details Advanced Grant (AdG), LS5, ERC-2011-ADG_20110310
Summary "The ambitious goal of this proposal is to identify causal mechanisms in schizophrenia, a devastating disease affecting about 1 percent of the population worldwide, and for which there is no current prevention or cure.
If my team and I are successful, we will discover etiological factors that can be targets for preventive interventions on the general population level and in high-risk groups, as well as inform the development of novel treatments.
I will use a truly unique population-based set of registers and biobanks, based upon a total national Danish birth cohort of more that 1.6 million individuals, and apply a novel combination of epidemiological design and methods and molecular biological techniques to the study of early risk factors for schizophrenia: I propose to combine cohort, nested case-control and case-sibling designs in studies of this total national birth cohort with detailed biological assessment of genetic and environmental risk factors operating during fetal life and around birth, in combination with detailed longitudinal information about the life course of cases, controls and their relatives.
Together with my team, I will for the first time in a human population empirically test a range of novel and specific hypotheses, tied together by a common theoretical framework of inflammatory and immune mechanisms interacting with individual genetic vulnerability during fetal life. Specifically the focus will be on infectious agents, markers of inflammation, effects of maternal auto-antibodies, and interactions with maternal vitamin D as well as genes involved in apoptosis and other relevant pathways. All findings will be tested in independent replication samples from the same population and further validated by comparison to healthy sibling controls. Because my studies are performed in a total population birth cohort, we will be able to make risk prediction suitable for the identification of targets for preventive strategies."
Summary
"The ambitious goal of this proposal is to identify causal mechanisms in schizophrenia, a devastating disease affecting about 1 percent of the population worldwide, and for which there is no current prevention or cure.
If my team and I are successful, we will discover etiological factors that can be targets for preventive interventions on the general population level and in high-risk groups, as well as inform the development of novel treatments.
I will use a truly unique population-based set of registers and biobanks, based upon a total national Danish birth cohort of more that 1.6 million individuals, and apply a novel combination of epidemiological design and methods and molecular biological techniques to the study of early risk factors for schizophrenia: I propose to combine cohort, nested case-control and case-sibling designs in studies of this total national birth cohort with detailed biological assessment of genetic and environmental risk factors operating during fetal life and around birth, in combination with detailed longitudinal information about the life course of cases, controls and their relatives.
Together with my team, I will for the first time in a human population empirically test a range of novel and specific hypotheses, tied together by a common theoretical framework of inflammatory and immune mechanisms interacting with individual genetic vulnerability during fetal life. Specifically the focus will be on infectious agents, markers of inflammation, effects of maternal auto-antibodies, and interactions with maternal vitamin D as well as genes involved in apoptosis and other relevant pathways. All findings will be tested in independent replication samples from the same population and further validated by comparison to healthy sibling controls. Because my studies are performed in a total population birth cohort, we will be able to make risk prediction suitable for the identification of targets for preventive strategies."
Max ERC Funding
2 471 736 €
Duration
Start date: 2012-05-01, End date: 2017-04-30
Project acronym ElectroThermo
Project New Paradigm in Electrolyte Thermodynamics
Researcher (PI) Georgios KONTOGEORGIS
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Advanced Grant (AdG), PE8, ERC-2018-ADG
Summary The project’s overall target is to arrive at a fundamental understanding of electrolyte thermodynamics and thus enable the engineering of a new generation of useful, physically sound models for electrolyte solutions. These models should be general and applicable to a very wide range of conditions so that they can be potentially used for a wide range of applications.
Electrolyte solutions are present almost anywhere and find numerous applications in physical sciences including chemistry, geology, material science, medicine, biochemistry and physiology as well as in many engineering fields especially chemical & biochemical, electrical and petroleum engineering. In all these applications the thermodynamics plays a crucial role over wide ranges of temperature, pressure and composition. As the subject is important, a relatively large body of knowledge has been accumulated with lots of data and models. However, disappointingly the state-of-the art thermodynamic models used today in engineering practice are semi-empirical and require numerous experimental data. They lack generality and have not enhanced our understanding of electrolyte thermodynamics. Going beyond the current state of the art, we will create the scientific foundation for studying, at their extremes, both “primitive” and “non-primitive” approaches for electrolyte solutions and identify strengths and limitations. The project is based on the PI’s many years of experience in thermodynamics. The ambition is to make new advances to clarify major questions and misunderstandings in electrolyte thermodynamics, some remaining for over 100 years, which currently prevent real progress from being made, and create a new paradigm which will ultimately pave the way for the development of new engineering models for electrolyte solutions. This is a risky, ambitious and crucial task, but a successful completion will have significant benefits in many industrial sectors as well as in environmental studies and biotechnology.
Summary
The project’s overall target is to arrive at a fundamental understanding of electrolyte thermodynamics and thus enable the engineering of a new generation of useful, physically sound models for electrolyte solutions. These models should be general and applicable to a very wide range of conditions so that they can be potentially used for a wide range of applications.
Electrolyte solutions are present almost anywhere and find numerous applications in physical sciences including chemistry, geology, material science, medicine, biochemistry and physiology as well as in many engineering fields especially chemical & biochemical, electrical and petroleum engineering. In all these applications the thermodynamics plays a crucial role over wide ranges of temperature, pressure and composition. As the subject is important, a relatively large body of knowledge has been accumulated with lots of data and models. However, disappointingly the state-of-the art thermodynamic models used today in engineering practice are semi-empirical and require numerous experimental data. They lack generality and have not enhanced our understanding of electrolyte thermodynamics. Going beyond the current state of the art, we will create the scientific foundation for studying, at their extremes, both “primitive” and “non-primitive” approaches for electrolyte solutions and identify strengths and limitations. The project is based on the PI’s many years of experience in thermodynamics. The ambition is to make new advances to clarify major questions and misunderstandings in electrolyte thermodynamics, some remaining for over 100 years, which currently prevent real progress from being made, and create a new paradigm which will ultimately pave the way for the development of new engineering models for electrolyte solutions. This is a risky, ambitious and crucial task, but a successful completion will have significant benefits in many industrial sectors as well as in environmental studies and biotechnology.
Max ERC Funding
2 500 000 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
