Project acronym ANINAN
Project An Intersectional Analysis of Ancient Jewish Travel Narratives
Researcher (PI) Elisa Katariina UUSIMaeKI
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), SH5, ERC-2020-STG
Summary ANINAN investigates literary and cultural representations of travel and mobility – the often temporary move of a person from her or his home to another location – in ancient Israelite/Jewish narratives, including selected texts of the Hebrew Bible and other Jewish writings from the Hellenistic and early Roman eras (ca. 300 BCE – 100 CE). The sources, which originate from different parts of the Mediterranean region, are written or preserved in Hebrew, Aramaic, Greek, Latin, and Ge’ez.
The aim is to understand how human mobility was perceived and/or imagined in Jewish antiquity, including its agents, motives, and outcomes. The main objectives are: (1) to produce a series of case-studies that illustrate the portrayal of human mobility and its social confines in Israelite/Jewish literature; and (2) to compare and theorize the cultural representations of travel in an intersectional frame and, as a result, to provide a ground-breaking interpretative framework for the study of mobility in texts from the human past. The selected intersectional approach is novel and specifically unearths questions of power and social stratification that evidently pertain to (in)voluntary forms of mobility, including the individual profile of the traveller and the social realities that prompted, enabled, or compelled her or his travel in the first place.
The challenge is that we know nothing about the power dynamics of ancient Israelite/Jewish travel accounts. They are expected to reveal striking intersectional concerns, highlighting the complexity of human phenomena such as mobility. While multiple ‘categories of difference’ characterize the travelling agents, mobility also affects and shapes these categories, e.g., by leading the agent to negotiate, refine, or recreate aspects of her or his identity. The narratives also illustrate encounters between the Israelites/Jews and ‘others’, which results in a new understanding of cultural interaction in the ancient eastern Mediterranean.
Summary
ANINAN investigates literary and cultural representations of travel and mobility – the often temporary move of a person from her or his home to another location – in ancient Israelite/Jewish narratives, including selected texts of the Hebrew Bible and other Jewish writings from the Hellenistic and early Roman eras (ca. 300 BCE – 100 CE). The sources, which originate from different parts of the Mediterranean region, are written or preserved in Hebrew, Aramaic, Greek, Latin, and Ge’ez.
The aim is to understand how human mobility was perceived and/or imagined in Jewish antiquity, including its agents, motives, and outcomes. The main objectives are: (1) to produce a series of case-studies that illustrate the portrayal of human mobility and its social confines in Israelite/Jewish literature; and (2) to compare and theorize the cultural representations of travel in an intersectional frame and, as a result, to provide a ground-breaking interpretative framework for the study of mobility in texts from the human past. The selected intersectional approach is novel and specifically unearths questions of power and social stratification that evidently pertain to (in)voluntary forms of mobility, including the individual profile of the traveller and the social realities that prompted, enabled, or compelled her or his travel in the first place.
The challenge is that we know nothing about the power dynamics of ancient Israelite/Jewish travel accounts. They are expected to reveal striking intersectional concerns, highlighting the complexity of human phenomena such as mobility. While multiple ‘categories of difference’ characterize the travelling agents, mobility also affects and shapes these categories, e.g., by leading the agent to negotiate, refine, or recreate aspects of her or his identity. The narratives also illustrate encounters between the Israelites/Jews and ‘others’, which results in a new understanding of cultural interaction in the ancient eastern Mediterranean.
Max ERC Funding
1 368 977 €
Duration
Start date: 2021-02-01, End date: 2026-01-31
Project acronym CIRCUITASSEMBLY
Project Development of functional organization of the visual circuits in mice
Researcher (PI) Keisuke Yonehara
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
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 ENVNANO
Project Environmental Effects and Risk Evaluation of Engineered Nanoparticles
Researcher (PI) Anders Baun
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS9, ERC-2011-StG_20101109
Summary The objective of the project Environmental Effects and Risk Evaluation of Engineered Nanoparticles (EnvNano) is to elucidate the particle specific properties that govern the ecotoxicological effects of engineered nanoparticles and in this way shift the paradigm for environmental risk assessment of nanomaterials.
While current activities in the emerging field of nano-ecotoxicology and environmental risk assessment of nanomaterials are based on the assumption that the methodologies developed for chemicals can be adapted to be applicable for nanomaterials, EnvNano has a completely different starting point: The behaviour of nanoparticles in suspension is fundamentally different from that of chemicals in on solution.
Therefore, all modifications of existing techniques that do not take this fact into account are bound to have a limited sphere of application or in the worst case to be invalid. By replacing the assumption of dissolved chemicals with a particle behaviour assumption, the traditional risk assessment paradigm will be so seriously impaired that a shift of paradigm will be needed.
EnvNano is based on the following hypotheses: 1. The ecotoxicity and bioaccumulation of engineered nanoparticles will be a function of specific physical and chemical characteristics of the nanoparticles; 2. The environmental hazards of engineered nanoparticles cannot be derived from hazard identifications of the material in other forms; 3. Existing regulatory risk assessment procedures for chemicals will not be appropriate to assess the behaviour and potential harmful effects of engineered nanoparticles on the environment.
These research hypotheses will be addressed in the four interacting research topics of EnvNano: Particle Characterization, Ecotoxicty, Bioaccumulation, and Framework for Risk Evaluation of Nanoparticles aimed to form the foundation for a movement from coefficient-based to kinetic-based environmental nanotoxicology and risk assessment.
Summary
The objective of the project Environmental Effects and Risk Evaluation of Engineered Nanoparticles (EnvNano) is to elucidate the particle specific properties that govern the ecotoxicological effects of engineered nanoparticles and in this way shift the paradigm for environmental risk assessment of nanomaterials.
While current activities in the emerging field of nano-ecotoxicology and environmental risk assessment of nanomaterials are based on the assumption that the methodologies developed for chemicals can be adapted to be applicable for nanomaterials, EnvNano has a completely different starting point: The behaviour of nanoparticles in suspension is fundamentally different from that of chemicals in on solution.
Therefore, all modifications of existing techniques that do not take this fact into account are bound to have a limited sphere of application or in the worst case to be invalid. By replacing the assumption of dissolved chemicals with a particle behaviour assumption, the traditional risk assessment paradigm will be so seriously impaired that a shift of paradigm will be needed.
EnvNano is based on the following hypotheses: 1. The ecotoxicity and bioaccumulation of engineered nanoparticles will be a function of specific physical and chemical characteristics of the nanoparticles; 2. The environmental hazards of engineered nanoparticles cannot be derived from hazard identifications of the material in other forms; 3. Existing regulatory risk assessment procedures for chemicals will not be appropriate to assess the behaviour and potential harmful effects of engineered nanoparticles on the environment.
These research hypotheses will be addressed in the four interacting research topics of EnvNano: Particle Characterization, Ecotoxicty, Bioaccumulation, and Framework for Risk Evaluation of Nanoparticles aimed to form the foundation for a movement from coefficient-based to kinetic-based environmental nanotoxicology and risk assessment.
Max ERC Funding
1 196 260 €
Duration
Start date: 2011-12-01, End date: 2016-03-31
Project acronym miPDesign
Project Designing microProteins to alter growth processes in crop plants
Researcher (PI) Stephan Wenkel
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS9, ERC-2013-StG
Summary The directed control of protein activity plays a crucial role in the regulation of growth and development of multicellular organisms. Different post-translational control mechanisms are known to influence the activity of proteins. Here, I am proposing a novel way to control the activity of proteins that function as multimeric complexes. MicroProteins, are small single-domain protein species that can influence target proteins by sequestering them into non-productive protein complexes. I have developed the concept of microProtein function and subsequently started to identify novel microProtein regulators in the model plant Arabidopsis. The aim of this proposal is to use the microProtein concept and build synthetic microProtein modules in economical import crop plants. By combining synthetic biology approaches with modern plant breeding, we intent to re-wire plant development and alter the flowering behaviour of rice. In addition, we will use a combination of artificial microProteins and microProtein-resistant transcription factors to modify the inclination angle of leaves in rice and the bioenergy model species Brachypodium distachion. Modification of the leaf angle will allow us to grow crops at higher densities, thus having the potential to increase both biomass and seed production per acreage. Finally, we aim to identify novel, evolutionary conserved microProtein-modules and unravel the mechanism of microProtein function, to study their role in plant development and adaptation.
Summary
The directed control of protein activity plays a crucial role in the regulation of growth and development of multicellular organisms. Different post-translational control mechanisms are known to influence the activity of proteins. Here, I am proposing a novel way to control the activity of proteins that function as multimeric complexes. MicroProteins, are small single-domain protein species that can influence target proteins by sequestering them into non-productive protein complexes. I have developed the concept of microProtein function and subsequently started to identify novel microProtein regulators in the model plant Arabidopsis. The aim of this proposal is to use the microProtein concept and build synthetic microProtein modules in economical import crop plants. By combining synthetic biology approaches with modern plant breeding, we intent to re-wire plant development and alter the flowering behaviour of rice. In addition, we will use a combination of artificial microProteins and microProtein-resistant transcription factors to modify the inclination angle of leaves in rice and the bioenergy model species Brachypodium distachion. Modification of the leaf angle will allow us to grow crops at higher densities, thus having the potential to increase both biomass and seed production per acreage. Finally, we aim to identify novel, evolutionary conserved microProtein-modules and unravel the mechanism of microProtein function, to study their role in plant development and adaptation.
Max ERC Funding
1 443 320 €
Duration
Start date: 2013-12-01, End date: 2018-11-30
Project acronym MOS
Project Manifestations of Solitude: Withdrawal and Engagement in the long seventeenth-century
Researcher (PI) Mette Birkedal Bruun
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), SH5, ERC-2012-StG_20111124
Summary The objective of Manifestations of Solitude: Withdrawal and Engagement in the long seventeenth-century is to demonstrate how the creation of zones of unworldliness within the world structures re-ligious practice. We will examine withdrawal in its historical settings and uncover the facetted na-ture of this phenomenon in the seventeenth-century religious culture, thus offering insights and tools for a better understanding of the representation of religious experience in European culture.
Working across cultural and confessional boundaries, the project explores appropriations of the appeal that the Christian be in the world but not of the world: in texts, architecture, images and mu-sic, and it examines the ways in which these media are employed to prompt and sustain with¬drawal from the world. The project focuses on ten institutional social units (e.g. the abbey, the Konventikel, the household), which manifest solitude in different ways. It examines such units through ten exem-plary places (e.g. Herrnhut, Saint-Cyr) and their cultural and reli¬gious life, drawing on materials such as architectural plans, interior decoration, treatises on theology and aesthetics, letters, diaries, epitaphs, emblems, portraits, devotional images, sermons and musical pieces.
The backbone of the project is an innovative strategy for interdisciplinary analysis which traces the generation of a symbolically charged space around religious withdrawals. With this analytical tool we will examine how symbols of ‘world’, ‘solitude’ and the demarcation between them are materialized in forms ranging from material culture (architecture, furnishing), via artistic, perfor-mative expressions (devotional images, musical pieces) to literary topoi and metaphors and the in-fluence on such forms of contemporary aesthetic sensibilities. The project examines the cultivation of the religious self: shaping a sym¬bolically charged space – and shaped in turn by this space.
Summary
The objective of Manifestations of Solitude: Withdrawal and Engagement in the long seventeenth-century is to demonstrate how the creation of zones of unworldliness within the world structures re-ligious practice. We will examine withdrawal in its historical settings and uncover the facetted na-ture of this phenomenon in the seventeenth-century religious culture, thus offering insights and tools for a better understanding of the representation of religious experience in European culture.
Working across cultural and confessional boundaries, the project explores appropriations of the appeal that the Christian be in the world but not of the world: in texts, architecture, images and mu-sic, and it examines the ways in which these media are employed to prompt and sustain with¬drawal from the world. The project focuses on ten institutional social units (e.g. the abbey, the Konventikel, the household), which manifest solitude in different ways. It examines such units through ten exem-plary places (e.g. Herrnhut, Saint-Cyr) and their cultural and reli¬gious life, drawing on materials such as architectural plans, interior decoration, treatises on theology and aesthetics, letters, diaries, epitaphs, emblems, portraits, devotional images, sermons and musical pieces.
The backbone of the project is an innovative strategy for interdisciplinary analysis which traces the generation of a symbolically charged space around religious withdrawals. With this analytical tool we will examine how symbols of ‘world’, ‘solitude’ and the demarcation between them are materialized in forms ranging from material culture (architecture, furnishing), via artistic, perfor-mative expressions (devotional images, musical pieces) to literary topoi and metaphors and the in-fluence on such forms of contemporary aesthetic sensibilities. The project examines the cultivation of the religious self: shaping a sym¬bolically charged space – and shaped in turn by this space.
Max ERC Funding
1 250 000 €
Duration
Start date: 2013-02-01, End date: 2017-03-31
Project acronym REFOCUS
Project Chip-Scale Self-Referenced Optical Frequency Comb Sources
Researcher (PI) Minhao Pu
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), PE7, ERC-2019-STG
Summary As a Nobel-honored technology, optical frequency combs, which consist of equidistant spectral lines, have revolutionized applications in time-keeping, and metrology as they offer unprecedented precision in frequency via self-referencing. However, conventional frequency comb systems have been confined to laboratories due to the cost, size, and power requirements of their components. This project aims to develop a chip-scale optical frequency comb source that can be self-referenced.
Key components to realize self-referencing are comb generators and frequency doublers. However, it is challenging to integrate both functionalities on the same chip as they typically rely on different nonlinear processes and thus different material platforms. Another major challenge in the system miniaturization is how to achieve ultra-efficient comb generation and frequency doubling to enable on-chip comb pumping and self-referencing beat note detection, respectively.
In this project, we will circumvent the multi-material issue by developing both comb generator and frequency doubler based on the same nonlinear material: aluminum gallium arsenide (AlGaAs). This material exhibits both strong cubic and quadratic nonlinearities which can be utilized for comb generation and frequency doubling, respectively. Ultra-efficient comb generation will be realized by developing ultra-high-quality-factor microresonators and employing new comb generation methods combining cubic and quadratic nonlinearities while highly-efficient frequency doubling will be achieved by adaptively-controlling the phase-matching condition. We will also develop heterogeneous integration technologies to bridge the nonlinear devices with on-chip laser sources and detectors by using intermediate silicon nitride circuits. Successful miniaturization of a self-referenced frequency comb source will enable applications like LIDAR, coherent communications, chemical sensing, medical imaging, and precision metrology.
Summary
As a Nobel-honored technology, optical frequency combs, which consist of equidistant spectral lines, have revolutionized applications in time-keeping, and metrology as they offer unprecedented precision in frequency via self-referencing. However, conventional frequency comb systems have been confined to laboratories due to the cost, size, and power requirements of their components. This project aims to develop a chip-scale optical frequency comb source that can be self-referenced.
Key components to realize self-referencing are comb generators and frequency doublers. However, it is challenging to integrate both functionalities on the same chip as they typically rely on different nonlinear processes and thus different material platforms. Another major challenge in the system miniaturization is how to achieve ultra-efficient comb generation and frequency doubling to enable on-chip comb pumping and self-referencing beat note detection, respectively.
In this project, we will circumvent the multi-material issue by developing both comb generator and frequency doubler based on the same nonlinear material: aluminum gallium arsenide (AlGaAs). This material exhibits both strong cubic and quadratic nonlinearities which can be utilized for comb generation and frequency doubling, respectively. Ultra-efficient comb generation will be realized by developing ultra-high-quality-factor microresonators and employing new comb generation methods combining cubic and quadratic nonlinearities while highly-efficient frequency doubling will be achieved by adaptively-controlling the phase-matching condition. We will also develop heterogeneous integration technologies to bridge the nonlinear devices with on-chip laser sources and detectors by using intermediate silicon nitride circuits. Successful miniaturization of a self-referenced frequency comb source will enable applications like LIDAR, coherent communications, chemical sensing, medical imaging, and precision metrology.
Max ERC Funding
1 487 597 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym SOCRATES
Project Serial Optical Communications for Advanced Terabit Ethernet Systems
Researcher (PI) Leif Katsuo Oxenloewe
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), PE7, ERC-2009-StG
Summary The last two decades has seen an explosion in telecommunication bandwidth, a trend which has never ceased. Another current trend is the growing concern for the environmental footprint humankind is leaving due to various industries. The Internet traffic grows roughly by 60% per year, and internet servers today consume about 2% of the total global electric power consumption corresponding to a CO2 emission approaching 1% of the total emission caused by human beings. These trends have made it very clear that it is imperative to develop new technologies that can accommodate for the ever growing bandwidth demand and reduce power consumption. The key issue for modern telecommunication engineers and designers is no longer cost per bit, but power per bit. Using optical methods for carrying data and processing the data, without opto-to-electrical conversion, so-called all-optical methods, may help in this respect. This project will aim at developing an all-optical power-efficient communication scenario based on serial optical communications. In serial communications, fewer components will in general be used, and with ultra-short pulses, very high bit rates will become available. Historically, increases in the serial data rate have lead to cost savings, due to reduced complexity in management, reduced power consumption and a reduced number of components. We believe this will hold true, and will explore the fundamental physical limits of serial communications to reach the ultimate serial bit rate, and develop network scenarios to fully take advantage of the serial nature of the data, whilst maintaining a focus on limiting the power consumption. In particular we want to design network scenarios for optical serial multi-Tbit/s data and additionally build a 1 Tbit/s optical Ethernet scenario. We will develop stable ultra-fast switches , and mature them for a variety of functionalities, eventually leading to a validation of ultra-high-speed serial optical communication systems.
Summary
The last two decades has seen an explosion in telecommunication bandwidth, a trend which has never ceased. Another current trend is the growing concern for the environmental footprint humankind is leaving due to various industries. The Internet traffic grows roughly by 60% per year, and internet servers today consume about 2% of the total global electric power consumption corresponding to a CO2 emission approaching 1% of the total emission caused by human beings. These trends have made it very clear that it is imperative to develop new technologies that can accommodate for the ever growing bandwidth demand and reduce power consumption. The key issue for modern telecommunication engineers and designers is no longer cost per bit, but power per bit. Using optical methods for carrying data and processing the data, without opto-to-electrical conversion, so-called all-optical methods, may help in this respect. This project will aim at developing an all-optical power-efficient communication scenario based on serial optical communications. In serial communications, fewer components will in general be used, and with ultra-short pulses, very high bit rates will become available. Historically, increases in the serial data rate have lead to cost savings, due to reduced complexity in management, reduced power consumption and a reduced number of components. We believe this will hold true, and will explore the fundamental physical limits of serial communications to reach the ultimate serial bit rate, and develop network scenarios to fully take advantage of the serial nature of the data, whilst maintaining a focus on limiting the power consumption. In particular we want to design network scenarios for optical serial multi-Tbit/s data and additionally build a 1 Tbit/s optical Ethernet scenario. We will develop stable ultra-fast switches , and mature them for a variety of functionalities, eventually leading to a validation of ultra-high-speed serial optical communication systems.
Max ERC Funding
1 518 387 €
Duration
Start date: 2009-09-01, End date: 2014-08-31
Project acronym STC
Project Synaptic Tagging and Capture: From Synapses to Behavior
Researcher (PI) Sayyed Mohammad Sadegh Nabavi
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Starting Grant (StG), LS5, ERC-2015-STG
Summary It is shown that long-term potentiation (LTP) is the cellular basis of memory formation. However, since all but small fraction of memories are forgotten, LTP has been further divided into early LTP (e-LTP), the mechanism by which short-term memories are formed, and a more stable late LTP (L-LTP), by which long-term memories are formed. Remarkably, it has been shown that an e-LTP can be stabilized if it is preceded or followed by heterosynaptic L-LTP.
According to Synaptic Tagging and Capture (STC) hypothesis, e-LTP is stabilized by capturing proteins that are made by L-LTP induction. The model proposes that this mechanism underlies the formation of late associative memory, where the stability of a memory is not only defined by the stimuli that induce the change but also by events happening before and after these stimuli. As such, the model explicitly predicts that a short-term memory can be stabilized by inducing heterosynaptic L-LTP.
In this grant, I will put this hypothesis into test. Specifically, I will test two explicit predictions of STC model: 1) A naturally formed short-term memory can be stabilized by induction of heterosynaptic L-LTP. 2) This stabilization is caused by the protein synthesis feature of L-LTP. To do this, using optogenetics, I will engineer a short-term memory in auditory fear circuit, in which an animal transiently associates a foot shock to a tone. Subsequently, I will examine if optogenetic delivery of L-LTP to the visual inputs converging on the same population of neurons in the amygdala will stabilize the short-term tone fear memory.
To be able to engineer natural memory by manipulating synaptic plasticity I will develop two systems: 1) A two-color optical activation system which permits selective manipulation of distinct neuronal populations with precise temporal and spatial resolution; 2) An inducible and activity-dependent expression system by which those neurons that are activated by a natural stimulus will be optically tagged.
Summary
It is shown that long-term potentiation (LTP) is the cellular basis of memory formation. However, since all but small fraction of memories are forgotten, LTP has been further divided into early LTP (e-LTP), the mechanism by which short-term memories are formed, and a more stable late LTP (L-LTP), by which long-term memories are formed. Remarkably, it has been shown that an e-LTP can be stabilized if it is preceded or followed by heterosynaptic L-LTP.
According to Synaptic Tagging and Capture (STC) hypothesis, e-LTP is stabilized by capturing proteins that are made by L-LTP induction. The model proposes that this mechanism underlies the formation of late associative memory, where the stability of a memory is not only defined by the stimuli that induce the change but also by events happening before and after these stimuli. As such, the model explicitly predicts that a short-term memory can be stabilized by inducing heterosynaptic L-LTP.
In this grant, I will put this hypothesis into test. Specifically, I will test two explicit predictions of STC model: 1) A naturally formed short-term memory can be stabilized by induction of heterosynaptic L-LTP. 2) This stabilization is caused by the protein synthesis feature of L-LTP. To do this, using optogenetics, I will engineer a short-term memory in auditory fear circuit, in which an animal transiently associates a foot shock to a tone. Subsequently, I will examine if optogenetic delivery of L-LTP to the visual inputs converging on the same population of neurons in the amygdala will stabilize the short-term tone fear memory.
To be able to engineer natural memory by manipulating synaptic plasticity I will develop two systems: 1) A two-color optical activation system which permits selective manipulation of distinct neuronal populations with precise temporal and spatial resolution; 2) An inducible and activity-dependent expression system by which those neurons that are activated by a natural stimulus will be optically tagged.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-04-01, End date: 2022-03-31
Project acronym SWEETOOLS
Project Smart Biologics: Developing New Tools in Glycobiology
Researcher (PI) Milan Vrabel
Host Institution (HI) USTAV ORGANICKE CHEMIE A BIOCHEMIE, AV CR, V.V.I.
Country Czechia
Call Details Starting Grant (StG), LS9, ERC-2015-STG
Summary Glycans are ubiquitous biomolecules found throughout all kingdoms of life. Early studies contributed considerably to our appreciation of glycan functions by showing that abnormalities in the glycosylation can develop into pathogenesis and severe dysfunctions. Despite the crucial role of sugars in many biological events we still do not have adequate tools to decipher their complexity. To unveil the mysteries in the rapidly emerging field of glycobiology we aim in this proposal to develop new tools that will help us to study and understand these important biomolecules. To realize this, we plan to combine the unique targeting capability of biologics with the inhibitory effect of small molecules into robust constructs with advanced properties. The biological part of the construct will be evolved using synthetic peptide libraries ensuring high selectivity toward particular sugar processing enzymes. The second part of the construct will consist of small molecular inhibitor warhead that will be designed and synthesized based on crystal structure-aided analyses. To merge these two moieties we aim to develop a new target enzyme–templated fluorogenic in situ click chemistry methodology that will enable us to easily monitor and screen whole peptide–small molecule bioconjugate libraries as highly selective inhibitors and manipulators of sugar processing enzymes. In addition, we aim to create new multivalent heteroglycosystems by using bioorthogonal reactions on peptide library scaffold. These structures will enable us to study polyvalent carbohydrate–protein interactions and to generate novel therapeutics such as influenza virus entry blockers. Our goal is to develop a new class of smart bioconjugate probes that will help us to answer fundamental questions in glycobiology. The outcomes of this project will significantly deepen our knowledge of glycoconjugates and in the long term, will allow for the design of efficient vaccines and for the development of selective therapeutics.
Summary
Glycans are ubiquitous biomolecules found throughout all kingdoms of life. Early studies contributed considerably to our appreciation of glycan functions by showing that abnormalities in the glycosylation can develop into pathogenesis and severe dysfunctions. Despite the crucial role of sugars in many biological events we still do not have adequate tools to decipher their complexity. To unveil the mysteries in the rapidly emerging field of glycobiology we aim in this proposal to develop new tools that will help us to study and understand these important biomolecules. To realize this, we plan to combine the unique targeting capability of biologics with the inhibitory effect of small molecules into robust constructs with advanced properties. The biological part of the construct will be evolved using synthetic peptide libraries ensuring high selectivity toward particular sugar processing enzymes. The second part of the construct will consist of small molecular inhibitor warhead that will be designed and synthesized based on crystal structure-aided analyses. To merge these two moieties we aim to develop a new target enzyme–templated fluorogenic in situ click chemistry methodology that will enable us to easily monitor and screen whole peptide–small molecule bioconjugate libraries as highly selective inhibitors and manipulators of sugar processing enzymes. In addition, we aim to create new multivalent heteroglycosystems by using bioorthogonal reactions on peptide library scaffold. These structures will enable us to study polyvalent carbohydrate–protein interactions and to generate novel therapeutics such as influenza virus entry blockers. Our goal is to develop a new class of smart bioconjugate probes that will help us to answer fundamental questions in glycobiology. The outcomes of this project will significantly deepen our knowledge of glycoconjugates and in the long term, will allow for the design of efficient vaccines and for the development of selective therapeutics.
Max ERC Funding
1 405 625 €
Duration
Start date: 2016-02-01, End date: 2021-07-31
