Project acronym AGNES
Project ACTIVE AGEING – RESILIENCE AND EXTERNAL SUPPORT AS MODIFIERS OF THE DISABLEMENT OUTCOME
Researcher (PI) Taina Tuulikki RANTANEN
Host Institution (HI) JYVASKYLAN YLIOPISTO
Country Finland
Call Details Advanced Grant (AdG), SH3, ERC-2015-AdG
Summary The goals are 1. To develop a scale assessing the diversity of active ageing with four dimensions that are ability (what people can do), activity (what people do do), ambition (what are the valued activities that people want to do), and autonomy (how satisfied people are with the opportunity to do valued activities); 2. To examine health and physical and psychological functioning as the determinants and social and build environment, resilience and personal skills as modifiers of active ageing; 3. To develop a multicomponent sustainable intervention aiming to promote active ageing (methods: counselling, information technology, help from volunteers); 4. To test the feasibility and effectiveness on the intervention; and 5. To study cohort effects on the phenotypes on the pathway to active ageing.
“If You Can Measure It, You Can Change It.” Active ageing assessment needs conceptual progress, which I propose to do. A quantifiable scale will be developed that captures the diversity of active ageing stemming from the WHO definition of active ageing as the process of optimizing opportunities for health and participation in the society for all people in line with their needs, goals and capacities as they age. I will collect cross-sectional data (N=1000, ages 75, 80 and 85 years) and model the pathway to active ageing with state-of-the art statistical methods. By doing this I will create novel knowledge on preconditions for active ageing. The collected cohort data will be compared to a pre-existing cohort data that was collected 25 years ago to obtain knowledge about changes over time in functioning of older people. A randomized controlled trial (N=200) will be conducted to assess the effectiveness of the envisioned intervention promoting active ageing through participation. The project will regenerate ageing research by launching a novel scale, by training young scientists, by creating new concepts and theory development and by producing evidence for active ageing promotion
Summary
The goals are 1. To develop a scale assessing the diversity of active ageing with four dimensions that are ability (what people can do), activity (what people do do), ambition (what are the valued activities that people want to do), and autonomy (how satisfied people are with the opportunity to do valued activities); 2. To examine health and physical and psychological functioning as the determinants and social and build environment, resilience and personal skills as modifiers of active ageing; 3. To develop a multicomponent sustainable intervention aiming to promote active ageing (methods: counselling, information technology, help from volunteers); 4. To test the feasibility and effectiveness on the intervention; and 5. To study cohort effects on the phenotypes on the pathway to active ageing.
“If You Can Measure It, You Can Change It.” Active ageing assessment needs conceptual progress, which I propose to do. A quantifiable scale will be developed that captures the diversity of active ageing stemming from the WHO definition of active ageing as the process of optimizing opportunities for health and participation in the society for all people in line with their needs, goals and capacities as they age. I will collect cross-sectional data (N=1000, ages 75, 80 and 85 years) and model the pathway to active ageing with state-of-the art statistical methods. By doing this I will create novel knowledge on preconditions for active ageing. The collected cohort data will be compared to a pre-existing cohort data that was collected 25 years ago to obtain knowledge about changes over time in functioning of older people. A randomized controlled trial (N=200) will be conducted to assess the effectiveness of the envisioned intervention promoting active ageing through participation. The project will regenerate ageing research by launching a novel scale, by training young scientists, by creating new concepts and theory development and by producing evidence for active ageing promotion
Max ERC Funding
2 044 364 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym Amygdala Circuits
Project Amygdala Circuits for Appetitive Conditioning
Researcher (PI) Andreas Luthi
Host Institution (HI) FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Country Switzerland
Call Details Advanced Grant (AdG), LS5, ERC-2014-ADG
Summary The project outlined here addresses the fundamental question how the brain encodes and controls behavior. While we have a reasonable understanding of the role of entire brain areas in such processes, and of mechanisms at the molecular and synaptic levels, there is a big gap in our knowledge of how behavior is controlled at the level of defined neuronal circuits.
In natural environments, chances for survival depend on learning about possible aversive and appetitive outcomes and on the appropriate behavioral responses. Most studies addressing the underlying mechanisms at the level of neuronal circuits have focused on aversive learning, such as in Pavlovian fear conditioning. Understanding how activity in defined neuronal circuits mediates appetitive learning, as well as how these circuitries are shared and interact with aversive learning circuits, is a central question in the neuroscience of learning and memory and the focus of this grant application.
Using a multidisciplinary approach in mice, combining behavioral, in vivo and in vitro electrophysiological, imaging, optogenetic and state-of-the-art viral circuit tracing techniques, we aim at dissecting the neuronal circuitry of appetitive Pavlovian conditioning with a focus on the amygdala, a key brain region important for both aversive and appetitive learning. Ultimately, elucidating these mechanisms at the level of defined neurons and circuits is fundamental not only for an understanding of memory processes in the brain in general, but also to inform a mechanistic approach to psychiatric conditions associated with amygdala dysfunction and dysregulated emotional responses including anxiety and mood disorders.
Summary
The project outlined here addresses the fundamental question how the brain encodes and controls behavior. While we have a reasonable understanding of the role of entire brain areas in such processes, and of mechanisms at the molecular and synaptic levels, there is a big gap in our knowledge of how behavior is controlled at the level of defined neuronal circuits.
In natural environments, chances for survival depend on learning about possible aversive and appetitive outcomes and on the appropriate behavioral responses. Most studies addressing the underlying mechanisms at the level of neuronal circuits have focused on aversive learning, such as in Pavlovian fear conditioning. Understanding how activity in defined neuronal circuits mediates appetitive learning, as well as how these circuitries are shared and interact with aversive learning circuits, is a central question in the neuroscience of learning and memory and the focus of this grant application.
Using a multidisciplinary approach in mice, combining behavioral, in vivo and in vitro electrophysiological, imaging, optogenetic and state-of-the-art viral circuit tracing techniques, we aim at dissecting the neuronal circuitry of appetitive Pavlovian conditioning with a focus on the amygdala, a key brain region important for both aversive and appetitive learning. Ultimately, elucidating these mechanisms at the level of defined neurons and circuits is fundamental not only for an understanding of memory processes in the brain in general, but also to inform a mechanistic approach to psychiatric conditions associated with amygdala dysfunction and dysregulated emotional responses including anxiety and mood disorders.
Max ERC Funding
2 497 200 €
Duration
Start date: 2016-01-01, End date: 2020-12-31
Project acronym CleverGenes
Project Novel Gene Therapy Based on the Activation of Endogenous Genes for the Treatment of Ischemia - Concepts of endogenetherapy, release of promoter pausing, promoter-targeted ncRNAs and nuclear RNAi
Researcher (PI) Seppo Ylae-Herttuala
Host Institution (HI) ITA-SUOMEN YLIOPISTO
Country Finland
Call Details Advanced Grant (AdG), LS7, ERC-2014-ADG
Summary Background: Therapeutic angiogenesis with vascular endothelial growth factors (VEGFs) has great potential to become a novel, minimally invasive new treatment for a large number of patients with severe myocardial ischemia. However, this requires development of new technology. Advancing state-of-the-art: We propose a paradigm shift in gene therapy for chronic ischemia by activating endogenous VEGF-A,-B and -C genes and angiogenic transcription programs from the native promoters instead of gene transfer of exogenous cDNA to target tissues. We will develop a new platform technology (endogenetherapy) based on our novel concept of the release of promoter pausing and new promoter-targeted upregulating short hairpinRNAs, tissue-specific superenhancerRNAs activating specific transcription centers involving gene clusters in different chromosomal regions, small circularRNAs formed from self-splicing exons-introns that can be regulated with oligonucleotides and small molecules such as metabolites, nuclear RNAi vectors and specific CRISPR/gRNAmutatedCas9-VP16 technology with an ability to target integration into genomic safe harbor sites. After preclinical studies in mice and in a newly developed chronic cardiac ischemia model in pigs with special emphasis on the analysis of clinically relevant blood flow, metabolic and functional outcomes based on MRI, ultrasound, photoacoustic and PET imaging, the best construct will be taken to a phase I clinical study in patients with severe myocardial ischemia. Since endogenetherapy also involves epigenetic changes, which are reversible and long-lasting, we expect to efficiently activate natural angiogenic programs. Significance: If successful, this approach will begin a new era in gene therapy. Since there is a clear lack of technology capable of targeted upregulation of endogenous genes, the novel endogenetherapy approach may become widely applicable beyond cardiovascular diseases also in other areas of medicine and biomedical research.
Summary
Background: Therapeutic angiogenesis with vascular endothelial growth factors (VEGFs) has great potential to become a novel, minimally invasive new treatment for a large number of patients with severe myocardial ischemia. However, this requires development of new technology. Advancing state-of-the-art: We propose a paradigm shift in gene therapy for chronic ischemia by activating endogenous VEGF-A,-B and -C genes and angiogenic transcription programs from the native promoters instead of gene transfer of exogenous cDNA to target tissues. We will develop a new platform technology (endogenetherapy) based on our novel concept of the release of promoter pausing and new promoter-targeted upregulating short hairpinRNAs, tissue-specific superenhancerRNAs activating specific transcription centers involving gene clusters in different chromosomal regions, small circularRNAs formed from self-splicing exons-introns that can be regulated with oligonucleotides and small molecules such as metabolites, nuclear RNAi vectors and specific CRISPR/gRNAmutatedCas9-VP16 technology with an ability to target integration into genomic safe harbor sites. After preclinical studies in mice and in a newly developed chronic cardiac ischemia model in pigs with special emphasis on the analysis of clinically relevant blood flow, metabolic and functional outcomes based on MRI, ultrasound, photoacoustic and PET imaging, the best construct will be taken to a phase I clinical study in patients with severe myocardial ischemia. Since endogenetherapy also involves epigenetic changes, which are reversible and long-lasting, we expect to efficiently activate natural angiogenic programs. Significance: If successful, this approach will begin a new era in gene therapy. Since there is a clear lack of technology capable of targeted upregulation of endogenous genes, the novel endogenetherapy approach may become widely applicable beyond cardiovascular diseases also in other areas of medicine and biomedical research.
Max ERC Funding
2 437 500 €
Duration
Start date: 2015-11-01, End date: 2021-04-30
Project acronym CROSSLOCATIONS
Project Crosslocations in the Mediterranean: rethinking the socio-cultural dynamics of relative positioning
Researcher (PI) Sarah Francesca Green
Host Institution (HI) HELSINGIN YLIOPISTO
Country Finland
Call Details Advanced Grant (AdG), SH5, ERC-2015-AdG
Summary The Mediterranean, a key socio-cultural, economic and political crossroads, has shifted its relative position recently, with profound effects for relations between the peoples associated with its diverse parts. Crosslocations is a groundbreaking theoretical approach that goes beyond current borders research to analyse the significance of the changes in relations between places and peoples that this involves. It does this through explaining shifts in the relative positioning of the Mediterranean’s many locations – i.e. the changing values of where people are rather than who they are. Approaches focusing on people’s identities, statecraft or networks do not provide a way to research how the relative value of ‘being somewhere in particular’ is changing and diversifying.
The approach builds on the idea that in socio-cultural terms, location is a form of political, social, economic, and technical relative positioning, involving diverse scales that calibrate relative values (here called ‘locating regimes’). This means locations are both multiple and historically variable, so different types of location may overlap in the same geographical space, particularly in crossroads regions such as the Mediterranean. The dynamics between them alter relations between places, significantly affecting people’s daily lives, including their life chances, wellbeing, environmental, social and political conditions and status.
The project will first research the locating regimes crossing the Mediterranean region (border regimes, infrastructures; digital technologies; fiscal, financial and trading systems; environmental policies; and social and religious structures); then intensively ethnographically study the socio-cultural dynamics of relative positioning that these regimes generate in selected parts of the Mediterranean region. Through explaining the dynamics of relative location, Crosslocations will transform our understanding of trans-local, socio-cultural relations and separations.
Summary
The Mediterranean, a key socio-cultural, economic and political crossroads, has shifted its relative position recently, with profound effects for relations between the peoples associated with its diverse parts. Crosslocations is a groundbreaking theoretical approach that goes beyond current borders research to analyse the significance of the changes in relations between places and peoples that this involves. It does this through explaining shifts in the relative positioning of the Mediterranean’s many locations – i.e. the changing values of where people are rather than who they are. Approaches focusing on people’s identities, statecraft or networks do not provide a way to research how the relative value of ‘being somewhere in particular’ is changing and diversifying.
The approach builds on the idea that in socio-cultural terms, location is a form of political, social, economic, and technical relative positioning, involving diverse scales that calibrate relative values (here called ‘locating regimes’). This means locations are both multiple and historically variable, so different types of location may overlap in the same geographical space, particularly in crossroads regions such as the Mediterranean. The dynamics between them alter relations between places, significantly affecting people’s daily lives, including their life chances, wellbeing, environmental, social and political conditions and status.
The project will first research the locating regimes crossing the Mediterranean region (border regimes, infrastructures; digital technologies; fiscal, financial and trading systems; environmental policies; and social and religious structures); then intensively ethnographically study the socio-cultural dynamics of relative positioning that these regimes generate in selected parts of the Mediterranean region. Through explaining the dynamics of relative location, Crosslocations will transform our understanding of trans-local, socio-cultural relations and separations.
Max ERC Funding
2 433 234 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym CsnCRL
Project The molecular basis of CULLIN E3 ligase regulation by the COP9 signalosome
Researcher (PI) Nicolas Thoma
Host Institution (HI) FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Country Switzerland
Call Details Advanced Grant (AdG), LS1, ERC-2014-ADG
Summary Specificity in the ubiquitin-proteasome system is largely conferred by ubiquitin E3 ligases (E3s). Cullin-RING ligases (CRLs), constituting ~30% of all E3s in humans, mediate the ubiquitination of ~20% of the proteins degraded by the proteasome. CRLs are divided into seven families based on their cullin constituent. Each cullin binds a RING domain protein, and a vast repertoire of adaptor/substrate receptor modules, collectively creating more than 200 distinct CRLs. All CRLs are regulated by the COP9 signalosome (CSN), an eight-protein isopeptidase that removes the covalently attached activator, NEDD8, from the cullin. Independent of NEDD8 cleavage, CSN forms protective complexes with CRLs, which prevents destructive auto-ubiquitination.
The integrity of the CSN-CRL system is crucially important for the normal cell physiology. Based on our previous work on CRL structures (Fischer, et al., Nature 2014; Fischer, et al., Cell 2011) and that of isolated CSN (Lingaraju et al., Nature 2014), We now intend to provide the underlying molecular mechanism of CRL regulation by CSN. Structural insights at atomic resolution, combined with in vitro and in vivo functional studies are designed to reveal (i) how the signalosome deneddylates and maintains the bound ligases in an inactive state, (ii) how the multiple CSN subunits bind to structurally diverse CRLs, and (iii) how CSN is itself subject to regulation by post-translational modifications or additional further factors.
The ERC funding would allow my lab to pursue an ambitious interdisciplinary approach combining X-ray crystallography, cryo-electron microscopy, biochemistry and cell biology. This is expected to provide a unique molecular understanding of CSN action. Beyond ubiquitination, insight into this >13- subunit CSN-CRL assembly will allow examining general principles of multi-subunit complex action and reveal how the numerous, often essential, subunits contribute to complex function.
Summary
Specificity in the ubiquitin-proteasome system is largely conferred by ubiquitin E3 ligases (E3s). Cullin-RING ligases (CRLs), constituting ~30% of all E3s in humans, mediate the ubiquitination of ~20% of the proteins degraded by the proteasome. CRLs are divided into seven families based on their cullin constituent. Each cullin binds a RING domain protein, and a vast repertoire of adaptor/substrate receptor modules, collectively creating more than 200 distinct CRLs. All CRLs are regulated by the COP9 signalosome (CSN), an eight-protein isopeptidase that removes the covalently attached activator, NEDD8, from the cullin. Independent of NEDD8 cleavage, CSN forms protective complexes with CRLs, which prevents destructive auto-ubiquitination.
The integrity of the CSN-CRL system is crucially important for the normal cell physiology. Based on our previous work on CRL structures (Fischer, et al., Nature 2014; Fischer, et al., Cell 2011) and that of isolated CSN (Lingaraju et al., Nature 2014), We now intend to provide the underlying molecular mechanism of CRL regulation by CSN. Structural insights at atomic resolution, combined with in vitro and in vivo functional studies are designed to reveal (i) how the signalosome deneddylates and maintains the bound ligases in an inactive state, (ii) how the multiple CSN subunits bind to structurally diverse CRLs, and (iii) how CSN is itself subject to regulation by post-translational modifications or additional further factors.
The ERC funding would allow my lab to pursue an ambitious interdisciplinary approach combining X-ray crystallography, cryo-electron microscopy, biochemistry and cell biology. This is expected to provide a unique molecular understanding of CSN action. Beyond ubiquitination, insight into this >13- subunit CSN-CRL assembly will allow examining general principles of multi-subunit complex action and reveal how the numerous, often essential, subunits contribute to complex function.
Max ERC Funding
2 200 677 €
Duration
Start date: 2016-01-01, End date: 2021-02-28
Project acronym Filmcolors
Project Film Colors. An Interdisciplinary Approach.
Researcher (PI) Barbara Flueckiger
Host Institution (HI) UNIVERSITAT ZURICH
Country Switzerland
Call Details Advanced Grant (AdG), SH5, ERC-2014-ADG
Summary Film is in essence colored light projected onto a screen. Its aesthetics are thus highly determined by the material properties of film and the optical configuration of the cinematic apparatus. To this day, however, there is no systematic study of the relationship between the technology and aesthetics of film colors, despite the fact that, following the digital turn in film production and distribution, the understanding of this relationship is more essential than ever before.
Over 200 film color processes were developed since the invention of film. They are presented on the Timeline of Historical Film Colors, which will be an integral part of the project.
The groundbreaking nature of this project lies in a truly interdisciplinary research design with a novel methodology to explore the interaction of technological advances and limitations with film color aesthetics, identifying diachronic patterns of stylistic means. To this end it develops a tool through recent advancements in digital humanities for crowd-sourcing of color analyses of large groups of films. In-depth studies of technical papers and scientific measurements of film colors will investigate the technical basis of films’ aesthetic appearance. These insights will be applied to the digitization and restoration of historical films to explore and disseminate the results. While every serious art restoration connects scientific analyses with art-historical and aesthetic investigations, a similar approach is rarely applied to film.
In summary, the present research proposal capitalizes on the principal investigator’s preceding studies to bridge the gap between technology and aesthetics. With the methods described here, the results will trace previously hidden roots of aesthetic developments of film colors. While the project is ambitious, it builds on a sizable methodological foundation to optimize risk management and guarantee significant advances in the understanding of film colors.
Summary
Film is in essence colored light projected onto a screen. Its aesthetics are thus highly determined by the material properties of film and the optical configuration of the cinematic apparatus. To this day, however, there is no systematic study of the relationship between the technology and aesthetics of film colors, despite the fact that, following the digital turn in film production and distribution, the understanding of this relationship is more essential than ever before.
Over 200 film color processes were developed since the invention of film. They are presented on the Timeline of Historical Film Colors, which will be an integral part of the project.
The groundbreaking nature of this project lies in a truly interdisciplinary research design with a novel methodology to explore the interaction of technological advances and limitations with film color aesthetics, identifying diachronic patterns of stylistic means. To this end it develops a tool through recent advancements in digital humanities for crowd-sourcing of color analyses of large groups of films. In-depth studies of technical papers and scientific measurements of film colors will investigate the technical basis of films’ aesthetic appearance. These insights will be applied to the digitization and restoration of historical films to explore and disseminate the results. While every serious art restoration connects scientific analyses with art-historical and aesthetic investigations, a similar approach is rarely applied to film.
In summary, the present research proposal capitalizes on the principal investigator’s preceding studies to bridge the gap between technology and aesthetics. With the methods described here, the results will trace previously hidden roots of aesthetic developments of film colors. While the project is ambitious, it builds on a sizable methodological foundation to optimize risk management and guarantee significant advances in the understanding of film colors.
Max ERC Funding
2 913 144 €
Duration
Start date: 2015-09-01, End date: 2021-05-31
Project acronym INSEETO
Project In-situ second harmonic generation for emergent electronics in transition-metal oxides
Researcher (PI) Manfred FIEBIG
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Advanced Grant (AdG), PE3, ERC-2015-AdG
Summary Since transition-metal oxides heterostructures can be grown by pulsed laser deposition (PLD) with semiconductor-like accuracy, fascinating phases and functionalities derived from their spin-charge correlations have been discovered. So far, reflection high-energy electron diffraction is the only widely established technique for monitoring the structure and homogeneity of multilayers in-situ, while they are growing, and provide direct feedback information on how to optimise the growth process. With our proposal we will introduce second harmonic generation (SHG) as new in-situ technique that allows us to track spin-and charge-related phenomena such as ferroelectricity, (anti-) ferromagnetism, insulator-metal transitions, domain coupling effects or interface states in a non-invasive way throughout the deposition process. With this we are pursuing two goals: first, to establish SHG as new in-situ characterization technique in PLD which monitors strong spin-charge correlation effects while they emerge during growth; second, to apply in-situ SHG for tailoring novel functionalities in exemplary chosen types of transition-metal-oxide heterostructures of great current interest. These model systems are (i) proper ferroelectrics tuned to high-k dielectric response and improper ferroelectrics whose behaviour is determined by the unusual nature of the polar state; (ii) compounds in which the interplay of strain and defects leads to novel and reversibly tuneable states of matter; (iii) heterostructures with functionalities originating from the interaction across interfaces. In-situ SHG as new, property-monitoring tool in PLD has an immense potential to uncover new states of matter and functionalities. We are convinced that this will play an essential role in the leap towards the next generation of functional oxide heterostructures.
Summary
Since transition-metal oxides heterostructures can be grown by pulsed laser deposition (PLD) with semiconductor-like accuracy, fascinating phases and functionalities derived from their spin-charge correlations have been discovered. So far, reflection high-energy electron diffraction is the only widely established technique for monitoring the structure and homogeneity of multilayers in-situ, while they are growing, and provide direct feedback information on how to optimise the growth process. With our proposal we will introduce second harmonic generation (SHG) as new in-situ technique that allows us to track spin-and charge-related phenomena such as ferroelectricity, (anti-) ferromagnetism, insulator-metal transitions, domain coupling effects or interface states in a non-invasive way throughout the deposition process. With this we are pursuing two goals: first, to establish SHG as new in-situ characterization technique in PLD which monitors strong spin-charge correlation effects while they emerge during growth; second, to apply in-situ SHG for tailoring novel functionalities in exemplary chosen types of transition-metal-oxide heterostructures of great current interest. These model systems are (i) proper ferroelectrics tuned to high-k dielectric response and improper ferroelectrics whose behaviour is determined by the unusual nature of the polar state; (ii) compounds in which the interplay of strain and defects leads to novel and reversibly tuneable states of matter; (iii) heterostructures with functionalities originating from the interaction across interfaces. In-situ SHG as new, property-monitoring tool in PLD has an immense potential to uncover new states of matter and functionalities. We are convinced that this will play an essential role in the leap towards the next generation of functional oxide heterostructures.
Max ERC Funding
2 498 714 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym INTEGRATE
Project Central integration of metabolic and hedonic cues in metabolic health
Researcher (PI) Bernard Marie Thorens
Host Institution (HI) UNIVERSITE DE LAUSANNE
Country Switzerland
Call Details Advanced Grant (AdG), LS4, ERC-2015-AdG
Summary During evolution the brain has selected glucose as a main source of metabolic energy. This has imposed homeostatic and behavioral constraints. First, the glycemic levels must be maintained at a minimum of ~5 mM to ensure constant energy supply to the brain. Second, a high reward value has to be attributed to glucose-containing foods to increase the motivation to obtain them. These homeostatic and hedonic regulations depend on glucose sensing cells and neuronal circuits in the central nervous system. These cells and circuits regulate the activity of the sympathetic and parasympathetic nerves, which control the function of peripheral organs (liver, fat, muscles) and the secretion of glucagon and insulin by pancreatic islet cells. They also attribute a reward value to glucose-containing foods to control food-seeking behavior, a process that involves the mesolimbic dopaminergic system. Here, we will focus on three interrelated aims:
1. Identify the physiological role of glucose sensing neurons of the ventromedial hypothalamic nucleus (VMN, a key feeding and glucoregulatory center) in glucose homeostasis and food preference; identify their cellular diversity and their molecular make-up; and characterize their deregulations in metabolic diseases.
2. Characterize the molecular physiology of glucose sensing neurons of the paraventricular thalamus, which modulate the activity of the mesolimbic dopaminergic system to control motivated sucrose-seeking behavior; determine their control by other interoceptive signals, including from glucose sensing cells of the VMN.
3. Establish new molecular approaches to characterize, at the molecular and functional levels, the impact of early postnatal nutrition on the development and function of central glucose sensing cells in the control of adult animal physiology.
These studies will open-up new perspectives in the understanding of homeostatic and hedonic regulatory pathways, which preserve metabolic health over a lifetime.
Summary
During evolution the brain has selected glucose as a main source of metabolic energy. This has imposed homeostatic and behavioral constraints. First, the glycemic levels must be maintained at a minimum of ~5 mM to ensure constant energy supply to the brain. Second, a high reward value has to be attributed to glucose-containing foods to increase the motivation to obtain them. These homeostatic and hedonic regulations depend on glucose sensing cells and neuronal circuits in the central nervous system. These cells and circuits regulate the activity of the sympathetic and parasympathetic nerves, which control the function of peripheral organs (liver, fat, muscles) and the secretion of glucagon and insulin by pancreatic islet cells. They also attribute a reward value to glucose-containing foods to control food-seeking behavior, a process that involves the mesolimbic dopaminergic system. Here, we will focus on three interrelated aims:
1. Identify the physiological role of glucose sensing neurons of the ventromedial hypothalamic nucleus (VMN, a key feeding and glucoregulatory center) in glucose homeostasis and food preference; identify their cellular diversity and their molecular make-up; and characterize their deregulations in metabolic diseases.
2. Characterize the molecular physiology of glucose sensing neurons of the paraventricular thalamus, which modulate the activity of the mesolimbic dopaminergic system to control motivated sucrose-seeking behavior; determine their control by other interoceptive signals, including from glucose sensing cells of the VMN.
3. Establish new molecular approaches to characterize, at the molecular and functional levels, the impact of early postnatal nutrition on the development and function of central glucose sensing cells in the control of adult animal physiology.
These studies will open-up new perspectives in the understanding of homeostatic and hedonic regulatory pathways, which preserve metabolic health over a lifetime.
Max ERC Funding
2 499 714 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym Local State
Project State Formation Through the Local Production of Property and Citizenship
Researcher (PI) Christian Lund
Host Institution (HI) KOBENHAVNS UNIVERSITET
Country Denmark
Call Details Advanced Grant (AdG), SH2, ERC-2014-ADG
Summary The key concern of the proposed research is how political power is established and reproduced through the production of the fundamental social contracts of property and citizenship. We will re-define the research on so-called failed and weak states, by examining what political authority is actually exercised rather than measuring how they fall short of theoretical ideals.
In developing countries with legal and institutional pluralism, no single institution exercises the political authority as such. Different institutions compete to define and enforce rights to property and citizenship. This is most visible at the local level, yet it has implications for theorizing the state as such. Hence, investigating the social production of property and citizenship is a way to study state formation. We study local institutions that exercise political authority and govern access to resources, and recognition of these rights. What institution guarantees what claims as rights, and, especially, how, is crucial, as it leads to the recognition of that particular institution as a political authority. We therefore study statutory as well as non-statutory institutions. We are not simply looking for property deeds and passports etc. issued by statutory government as measurements of political authority. Rather, we look for secondary forms of recognition ‘issued’ by non-statutory institutions that represent mutual acknowledgements of claims even without a narrow legal endorsement. Dynamics such as these are fundamental for a concise understanding of developing country state formation processes.
Ten country studies with rural and urban field sites will be conducted. We focus on concrete controversies. We collect data at several levels and from different sources, including resident groups, land users, local civil servants, local politicians and business-owners, as well as large-scale contractors, municipal politicians and administrators.
Summary
The key concern of the proposed research is how political power is established and reproduced through the production of the fundamental social contracts of property and citizenship. We will re-define the research on so-called failed and weak states, by examining what political authority is actually exercised rather than measuring how they fall short of theoretical ideals.
In developing countries with legal and institutional pluralism, no single institution exercises the political authority as such. Different institutions compete to define and enforce rights to property and citizenship. This is most visible at the local level, yet it has implications for theorizing the state as such. Hence, investigating the social production of property and citizenship is a way to study state formation. We study local institutions that exercise political authority and govern access to resources, and recognition of these rights. What institution guarantees what claims as rights, and, especially, how, is crucial, as it leads to the recognition of that particular institution as a political authority. We therefore study statutory as well as non-statutory institutions. We are not simply looking for property deeds and passports etc. issued by statutory government as measurements of political authority. Rather, we look for secondary forms of recognition ‘issued’ by non-statutory institutions that represent mutual acknowledgements of claims even without a narrow legal endorsement. Dynamics such as these are fundamental for a concise understanding of developing country state formation processes.
Ten country studies with rural and urban field sites will be conducted. We focus on concrete controversies. We collect data at several levels and from different sources, including resident groups, land users, local civil servants, local politicians and business-owners, as well as large-scale contractors, municipal politicians and administrators.
Max ERC Funding
2 469 285 €
Duration
Start date: 2016-01-01, End date: 2021-06-30
Project acronym MemoryDynamics
Project Writing and editing of memories from acquisition to long-term consolidation
Researcher (PI) Pierenrico CARONI
Host Institution (HI) FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Country Switzerland
Call Details Advanced Grant (AdG), LS5, ERC-2015-AdG
Summary Nervous systems produce adaptive behavior, arguably their most important function, through learning and memory. Memories ensure that what is learned will be available for later retrieval. Upon the initial learning process, synaptic plasticity important for memory consolidation is triggered within minutes, but whether, and in which form memories will be retained more permanently can be influenced by information and insights gained after the initial trigger. Learning and memory have been studied extensively, but we still know very little about the mechanisms through which memories are shaped after acquisition. Here we hypothesize that instead of simply reflecting requirements to produce long-term memory traces, cascades of plasticity processes induced at the time of acquisition might also reflect systems requirements for updating of new relevant information, as well as selection of potentially useful memories that need to enter the process of long-term consolidation.
Recent advances in neuroscience have provided powerful novel means to reveal, analyze and manipulate memory traces in the living brain, from single neurons to systems, and to interrogate their function. This research program will address the functional roles of learning-related plasticity processes unfolding subsequent to acquisition in learning and memory. We will investigate how hippocampal memories are shaped during several hours after acquisition through network activity and addition of new information through experience, and how these processes involve unique roles for dorsal hippocampus, and for dedicated neuronal circuits. Furthermore, we will study how shaped memories are then long-term consolidated, including the key role of ventral hippocampal circuitry, and how memories are further modified through subsequent learning. This research will produce fundamentally novel insights into how learning leads to adaptive behavior through writing and editing of memories.
Summary
Nervous systems produce adaptive behavior, arguably their most important function, through learning and memory. Memories ensure that what is learned will be available for later retrieval. Upon the initial learning process, synaptic plasticity important for memory consolidation is triggered within minutes, but whether, and in which form memories will be retained more permanently can be influenced by information and insights gained after the initial trigger. Learning and memory have been studied extensively, but we still know very little about the mechanisms through which memories are shaped after acquisition. Here we hypothesize that instead of simply reflecting requirements to produce long-term memory traces, cascades of plasticity processes induced at the time of acquisition might also reflect systems requirements for updating of new relevant information, as well as selection of potentially useful memories that need to enter the process of long-term consolidation.
Recent advances in neuroscience have provided powerful novel means to reveal, analyze and manipulate memory traces in the living brain, from single neurons to systems, and to interrogate their function. This research program will address the functional roles of learning-related plasticity processes unfolding subsequent to acquisition in learning and memory. We will investigate how hippocampal memories are shaped during several hours after acquisition through network activity and addition of new information through experience, and how these processes involve unique roles for dorsal hippocampus, and for dedicated neuronal circuits. Furthermore, we will study how shaped memories are then long-term consolidated, including the key role of ventral hippocampal circuitry, and how memories are further modified through subsequent learning. This research will produce fundamentally novel insights into how learning leads to adaptive behavior through writing and editing of memories.
Max ERC Funding
2 499 604 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
