Project acronym ALZSYN
Project Imaging synaptic contributors to dementia
Researcher (PI) Tara Spires-Jones
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Country United Kingdom
Call Details Consolidator Grant (CoG), LS5, ERC-2015-CoG
Summary Alzheimer's disease, the most common cause of dementia in older people, is a devastating condition that is becoming a public health crisis as our population ages. Despite great progress recently in Alzheimer’s disease research, we have no disease modifying drugs and a decade with a 99.6% failure rate of clinical trials attempting to treat the disease. This project aims to develop relevant therapeutic targets to restore brain function in Alzheimer’s disease by integrating human and model studies of synapses. It is widely accepted in the field that alterations in amyloid beta initiate the disease process. However the cascade leading from changes in amyloid to widespread tau pathology and neurodegeneration remain unclear. Synapse loss is the strongest pathological correlate of dementia in Alzheimer’s, and mounting evidence suggests that synapse degeneration plays a key role in causing cognitive decline. Here I propose to test the hypothesis that the amyloid cascade begins at the synapse leading to tau pathology, synapse dysfunction and loss, and ultimately neural circuit collapse causing cognitive impairment. The team will use cutting-edge multiphoton and array tomography imaging techniques to test mechanisms downstream of amyloid beta at synapses, and determine whether intervening in the cascade allows recovery of synapse structure and function. Importantly, I will combine studies in robust models of familial Alzheimer’s disease with studies in postmortem human brain to confirm relevance of our mechanistic studies to human disease. Finally, human stem cell derived neurons will be used to test mechanisms and potential therapeutics in neurons expressing the human proteome. Together, these experiments are ground-breaking since they have the potential to further our understanding of how synapses are lost in Alzheimer’s disease and to identify targets for effective therapeutic intervention, which is a critical unmet need in today’s health care system.
Summary
Alzheimer's disease, the most common cause of dementia in older people, is a devastating condition that is becoming a public health crisis as our population ages. Despite great progress recently in Alzheimer’s disease research, we have no disease modifying drugs and a decade with a 99.6% failure rate of clinical trials attempting to treat the disease. This project aims to develop relevant therapeutic targets to restore brain function in Alzheimer’s disease by integrating human and model studies of synapses. It is widely accepted in the field that alterations in amyloid beta initiate the disease process. However the cascade leading from changes in amyloid to widespread tau pathology and neurodegeneration remain unclear. Synapse loss is the strongest pathological correlate of dementia in Alzheimer’s, and mounting evidence suggests that synapse degeneration plays a key role in causing cognitive decline. Here I propose to test the hypothesis that the amyloid cascade begins at the synapse leading to tau pathology, synapse dysfunction and loss, and ultimately neural circuit collapse causing cognitive impairment. The team will use cutting-edge multiphoton and array tomography imaging techniques to test mechanisms downstream of amyloid beta at synapses, and determine whether intervening in the cascade allows recovery of synapse structure and function. Importantly, I will combine studies in robust models of familial Alzheimer’s disease with studies in postmortem human brain to confirm relevance of our mechanistic studies to human disease. Finally, human stem cell derived neurons will be used to test mechanisms and potential therapeutics in neurons expressing the human proteome. Together, these experiments are ground-breaking since they have the potential to further our understanding of how synapses are lost in Alzheimer’s disease and to identify targets for effective therapeutic intervention, which is a critical unmet need in today’s health care system.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym ASIBIA
Project Arctic sea ice, biogeochemistry and impacts on the atmosphere: Past, present, future
Researcher (PI) Roland Von Glasow
Host Institution (HI) UNIVERSITY OF EAST ANGLIA
Country United Kingdom
Call Details Consolidator Grant (CoG), PE10, ERC-2013-CoG
Summary The Arctic Ocean is a vast expanse of sea ice. Most of it is snow covered as are large continental regions for about half of the year. However, Global Change is arguably greatest in the Arctic, where temperatures have risen more than anywhere else in the last few decades. New record lows occurred in snow extent in June 2012 and sea ice extent in September 2012. Many observations show that widespread and sustained change is occurring in the Arctic driving this unique environmental system into a new state. This project focuses on the biogeochemical links between sea ice and snow and the composition and chemistry of the troposphere (the lowest ~10km of the atmosphere). This is an important topic because the concentrations of greenhouse gases and aerosol particles, which scatter sunlight directly and influence cloud properties, play key roles for our climate. Additionally, changes in the composition of the troposphere also affect the so-called oxidation capacity, the capability of the atmosphere to cleanse itself from pollutants.
This project aims to deliver a step change improvement in our quantitative understanding of chemical exchanges between ocean, sea ice, snow and the atmosphere in polar regions, especially the Arctic and of Arctic tropospheric chemistry. Answering these fundamental questions is essential to predict future change in the Arctic and globally. To this end a unique sea ice chamber will be constructed in the laboratory and used to quantify exchange processes in sea ice. Furthermore a hierarchy of numerical models will be used, operating at different spatial and temporal scales and degree of process description from a very detailed 1D to a global Earth System model. This will allow a breakthrough in our understanding of the importance of the changes for the composition and oxidation capacity of the atmosphere and climate and will allow us to calculate adjusted Greenhouse Warming Potentials that include these processes.
Summary
The Arctic Ocean is a vast expanse of sea ice. Most of it is snow covered as are large continental regions for about half of the year. However, Global Change is arguably greatest in the Arctic, where temperatures have risen more than anywhere else in the last few decades. New record lows occurred in snow extent in June 2012 and sea ice extent in September 2012. Many observations show that widespread and sustained change is occurring in the Arctic driving this unique environmental system into a new state. This project focuses on the biogeochemical links between sea ice and snow and the composition and chemistry of the troposphere (the lowest ~10km of the atmosphere). This is an important topic because the concentrations of greenhouse gases and aerosol particles, which scatter sunlight directly and influence cloud properties, play key roles for our climate. Additionally, changes in the composition of the troposphere also affect the so-called oxidation capacity, the capability of the atmosphere to cleanse itself from pollutants.
This project aims to deliver a step change improvement in our quantitative understanding of chemical exchanges between ocean, sea ice, snow and the atmosphere in polar regions, especially the Arctic and of Arctic tropospheric chemistry. Answering these fundamental questions is essential to predict future change in the Arctic and globally. To this end a unique sea ice chamber will be constructed in the laboratory and used to quantify exchange processes in sea ice. Furthermore a hierarchy of numerical models will be used, operating at different spatial and temporal scales and degree of process description from a very detailed 1D to a global Earth System model. This will allow a breakthrough in our understanding of the importance of the changes for the composition and oxidation capacity of the atmosphere and climate and will allow us to calculate adjusted Greenhouse Warming Potentials that include these processes.
Max ERC Funding
1 192 911 €
Duration
Start date: 2014-05-01, End date: 2016-09-30
Project acronym BYONIC
Project Beyond the Iron Curtain
Researcher (PI) Alessandro TAGLIABUE
Host Institution (HI) THE UNIVERSITY OF LIVERPOOL
Country United Kingdom
Call Details Consolidator Grant (CoG), PE10, ERC-2016-COG
Summary As one of the largest carbon reservoirs in the Earth system, the ocean is central to understanding past, present and future fluctuations in atmospheric carbon dioxide. In this context, microscopic plants called phytoplankton are key as they consume carbon dioxide during photosynthesis and transfer part of this carbon to the ocean’s interior and ultimately the lithosphere. The overall abundance of phytoplankton also forms the foundation of ocean food webs and drives the richness of marine fisheries.
It is key that we understand drivers of variations in phytoplankton growth, so we can explain changes in ocean productivity and the global carbon cycle, as well as project future trends with confidence. The numerical models we rely on for these tasks are prevented from doing so at present, however, due to a major theoretical gap concerning the role of trace metals in shaping phytoplankton growth in the ocean. This omission is particularly lacking at regional scales, where subtle interactions can lead to their co-limitation of biological activity. While we have long known that trace metals are fundamentally important to the photosynthesis and respiration of phytoplankton, it is only very recently that the necessary large-scale oceanic datasets required by numerical models have become available. I am leading such efforts with the trace metal iron, but we urgently need to expand our approach to other essential trace metals such as cobalt, copper, manganese and zinc.
This project will combine knowledge of biological requirement for trace metals with these newly emerging datasets to move ‘beyond the iron curtain’ and develop the first ever complete numerical model of resource limitation of phytoplankton growth, accounting for co-limiting interactions. Via a progressive combination of data synthesis and state of the art modelling, I will deliver a step-change into how we think resource availability controls life in the ocean.
Summary
As one of the largest carbon reservoirs in the Earth system, the ocean is central to understanding past, present and future fluctuations in atmospheric carbon dioxide. In this context, microscopic plants called phytoplankton are key as they consume carbon dioxide during photosynthesis and transfer part of this carbon to the ocean’s interior and ultimately the lithosphere. The overall abundance of phytoplankton also forms the foundation of ocean food webs and drives the richness of marine fisheries.
It is key that we understand drivers of variations in phytoplankton growth, so we can explain changes in ocean productivity and the global carbon cycle, as well as project future trends with confidence. The numerical models we rely on for these tasks are prevented from doing so at present, however, due to a major theoretical gap concerning the role of trace metals in shaping phytoplankton growth in the ocean. This omission is particularly lacking at regional scales, where subtle interactions can lead to their co-limitation of biological activity. While we have long known that trace metals are fundamentally important to the photosynthesis and respiration of phytoplankton, it is only very recently that the necessary large-scale oceanic datasets required by numerical models have become available. I am leading such efforts with the trace metal iron, but we urgently need to expand our approach to other essential trace metals such as cobalt, copper, manganese and zinc.
This project will combine knowledge of biological requirement for trace metals with these newly emerging datasets to move ‘beyond the iron curtain’ and develop the first ever complete numerical model of resource limitation of phytoplankton growth, accounting for co-limiting interactions. Via a progressive combination of data synthesis and state of the art modelling, I will deliver a step-change into how we think resource availability controls life in the ocean.
Max ERC Funding
1 668 418 €
Duration
Start date: 2017-06-01, End date: 2022-11-30
Project acronym ChaperoneRegulome
Project ChaperoneRegulome: Understanding cell-type-specificity of chaperone regulation
Researcher (PI) Ritwick SAWARKAR
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Consolidator Grant (CoG), LS3, ERC-2018-COG
Summary Protein misfolding causes devastating health conditions such as neurodegeneration. Although the disease-causing protein is widely expressed, its misfolding occurs only in certain cell-types such as neurons. What governs the susceptibility of some tissues to misfolding is a fundamental question with biomedical relevance.
Molecular chaperones help cellular proteins fold into their native conformation. Despite the generality of their function, chaperones are differentially expressed across various tissues. Moreover exposure to misfolding stress changes chaperone expression in a cell-type-dependent manner. Thus cell-type-specific regulation of chaperones is a major determinant of susceptibility to misfolding. The molecular mechanisms governing chaperone levels in different cell-types are not understood, forming the basis of this proposal. We will take a multidisciplinary approach to address two key questions: (1) How are chaperone levels co-ordinated with tissue-specific demands on protein folding? (2) How do different cell-types regulate chaperone genes when exposed to the same misfolding stress?
Cellular chaperone levels and their response to misfolding stress are both driven by transcriptional changes and influenced by chromatin. The proposed work will bring the conceptual, technological and computational advances of chromatin/ transcription field to understand chaperone biology and misfolding diseases. Using in vivo mouse model and in vitro differentiation model, we will investigate molecular mechanisms that control chaperone levels in relevant tissues. Our work will provide insights into functional specialization of chaperones driven by tissue-specific folding demands. We will develop a novel and ambitious approach to assess protein-folding capacity in single cells moving the chaperone field beyond state-of-the-art. Thus by implementing genetic, computational and biochemical approaches, we aim to understand cell-type-specificity of chaperone regulation.
Summary
Protein misfolding causes devastating health conditions such as neurodegeneration. Although the disease-causing protein is widely expressed, its misfolding occurs only in certain cell-types such as neurons. What governs the susceptibility of some tissues to misfolding is a fundamental question with biomedical relevance.
Molecular chaperones help cellular proteins fold into their native conformation. Despite the generality of their function, chaperones are differentially expressed across various tissues. Moreover exposure to misfolding stress changes chaperone expression in a cell-type-dependent manner. Thus cell-type-specific regulation of chaperones is a major determinant of susceptibility to misfolding. The molecular mechanisms governing chaperone levels in different cell-types are not understood, forming the basis of this proposal. We will take a multidisciplinary approach to address two key questions: (1) How are chaperone levels co-ordinated with tissue-specific demands on protein folding? (2) How do different cell-types regulate chaperone genes when exposed to the same misfolding stress?
Cellular chaperone levels and their response to misfolding stress are both driven by transcriptional changes and influenced by chromatin. The proposed work will bring the conceptual, technological and computational advances of chromatin/ transcription field to understand chaperone biology and misfolding diseases. Using in vivo mouse model and in vitro differentiation model, we will investigate molecular mechanisms that control chaperone levels in relevant tissues. Our work will provide insights into functional specialization of chaperones driven by tissue-specific folding demands. We will develop a novel and ambitious approach to assess protein-folding capacity in single cells moving the chaperone field beyond state-of-the-art. Thus by implementing genetic, computational and biochemical approaches, we aim to understand cell-type-specificity of chaperone regulation.
Max ERC Funding
1 992 500 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym CIL2015
Project Dissecting the cellular mechanics of contact inhibition of locomotion
Researcher (PI) Brian Marc Stramer
Host Institution (HI) KING'S COLLEGE LONDON
Country United Kingdom
Call Details Consolidator Grant (CoG), LS3, ERC-2015-CoG
Summary Our aim is to dissect the mechanisms of contact inhibition of locomotion (CIL), a process whereby migrating cells collide and repel each other, as it is now clear that CIL is pivotal to understanding embryogenesis and pathologies such as cancer. We have developed an in vivo model using Drosophila macrophages (hemocytes), along with novel analytical tools, to examine the contact inhibition response in cells during development. We therefore have an unprecedented opportunity to address CIL in a genetically tractable organism within a physiologically relevant setting. This model has revealed that a precisely controlled CIL response is a significant driving force behind the acquisition of embryonic patterns, and recent data show that this precision requires a series of synchronized changes in cytoskeletal dynamics. Our central hypothesis is that key to this cellular ‘dance’ is mechanosensation of the collision, which integrates subsequent signaling mechanisms to choreograph the steps of the contact inhibition process. The first part of this proposal will elucidate the molecular mechanisms controlling CIL by exploiting our unique ability to live image and genetically dissect this process in Drosophila. We will also take an interdisciplinary approach to elucidate the mechanical aspects of the response, which will allow us to examine the feedback between signaling pathways and the physical forces of the CIL response. We will subsequently extend our detailed understanding of the CIL process, and our novel set of analytical tools, to mammalian cell types and model systems. This will allow us to develop new assays to directly probe the mechanics of CIL and begin to investigate the function of this underexplored process in other cell types. This in depth knowledge of the response places us in the best position to extend our understanding of CIL to new physiologically relevant scenarios that in the future will impact on human health.
Summary
Our aim is to dissect the mechanisms of contact inhibition of locomotion (CIL), a process whereby migrating cells collide and repel each other, as it is now clear that CIL is pivotal to understanding embryogenesis and pathologies such as cancer. We have developed an in vivo model using Drosophila macrophages (hemocytes), along with novel analytical tools, to examine the contact inhibition response in cells during development. We therefore have an unprecedented opportunity to address CIL in a genetically tractable organism within a physiologically relevant setting. This model has revealed that a precisely controlled CIL response is a significant driving force behind the acquisition of embryonic patterns, and recent data show that this precision requires a series of synchronized changes in cytoskeletal dynamics. Our central hypothesis is that key to this cellular ‘dance’ is mechanosensation of the collision, which integrates subsequent signaling mechanisms to choreograph the steps of the contact inhibition process. The first part of this proposal will elucidate the molecular mechanisms controlling CIL by exploiting our unique ability to live image and genetically dissect this process in Drosophila. We will also take an interdisciplinary approach to elucidate the mechanical aspects of the response, which will allow us to examine the feedback between signaling pathways and the physical forces of the CIL response. We will subsequently extend our detailed understanding of the CIL process, and our novel set of analytical tools, to mammalian cell types and model systems. This will allow us to develop new assays to directly probe the mechanics of CIL and begin to investigate the function of this underexplored process in other cell types. This in depth knowledge of the response places us in the best position to extend our understanding of CIL to new physiologically relevant scenarios that in the future will impact on human health.
Max ERC Funding
1 993 803 €
Duration
Start date: 2016-09-01, End date: 2022-08-31
Project acronym CiliaCircuits
Project Molecular Principles of Mammalian Axonemal Dynein Assembly
Researcher (PI) Pleasantine Mill
Host Institution (HI) THE UNIVERSITY OF EDINBURGH
Country United Kingdom
Call Details Consolidator Grant (CoG), LS3, ERC-2019-COG
Summary Motile cilia are tiny microtubule-based projections which create fluid flow and are essential to human health. Cilia movement is powered by coordinated action of complex macromolecular motors, the axonemal dyneins. During differentiation, as cells produce hundreds of motile cilia, millions of dynein subunits must be pre-assembled in the cytoplasm into very large complexes in the correct stoichiometry which are then trafficked into growing cilia. This poses a sizeable challenge for the cell in terms of allocation of a significant fraction of the global translational machinery for streamlined assembly of dyneins within a crowded cellular space.
The key question remains: How does the cell know how much is enough? This is an extreme example of a common problem in cell biology. Responsive and adaptive mechanisms must exist to prevent futile expenditure of cellular resources in making a surplus of large molecules like dyneins that may also pose a risk of toxic aggregation. While a well-defined transcriptional code for induction of cilia motility genes exists, the translational dynamics and subsequent feedback circuitry coordinating dynein pre-assembly with ciliogenesis remain unexplored.
The molecular logic underlying the construction of motile cilia assembly are still not fully understood. The ambitious nature of CiliaCircuits proposes to use super-resolution and systems approaches to elucidate key mechanisms regulating this process in health and disease.
Human genetics tells us that making cilia motile is a complex process. To date, almost 40 genes have been implicated in primary ciliary dyskinesia (PCD), the disease of motile cilia, for which there is no cure. The long-term vision is to understand this dynamic control operating over a specialized proteome in time and space in order to develop effective PCD therapeutics and identify additional candidate genes involved in this translation regulation.
Summary
Motile cilia are tiny microtubule-based projections which create fluid flow and are essential to human health. Cilia movement is powered by coordinated action of complex macromolecular motors, the axonemal dyneins. During differentiation, as cells produce hundreds of motile cilia, millions of dynein subunits must be pre-assembled in the cytoplasm into very large complexes in the correct stoichiometry which are then trafficked into growing cilia. This poses a sizeable challenge for the cell in terms of allocation of a significant fraction of the global translational machinery for streamlined assembly of dyneins within a crowded cellular space.
The key question remains: How does the cell know how much is enough? This is an extreme example of a common problem in cell biology. Responsive and adaptive mechanisms must exist to prevent futile expenditure of cellular resources in making a surplus of large molecules like dyneins that may also pose a risk of toxic aggregation. While a well-defined transcriptional code for induction of cilia motility genes exists, the translational dynamics and subsequent feedback circuitry coordinating dynein pre-assembly with ciliogenesis remain unexplored.
The molecular logic underlying the construction of motile cilia assembly are still not fully understood. The ambitious nature of CiliaCircuits proposes to use super-resolution and systems approaches to elucidate key mechanisms regulating this process in health and disease.
Human genetics tells us that making cilia motile is a complex process. To date, almost 40 genes have been implicated in primary ciliary dyskinesia (PCD), the disease of motile cilia, for which there is no cure. The long-term vision is to understand this dynamic control operating over a specialized proteome in time and space in order to develop effective PCD therapeutics and identify additional candidate genes involved in this translation regulation.
Max ERC Funding
1 965 460 €
Duration
Start date: 2020-08-01, End date: 2025-07-31
Project acronym CLASS
Project Cross-Linguistic Acquisition of Sentence Structure: Integrating Experimental and Computational Approaches
Researcher (PI) Benjamin Ambridge
Host Institution (HI) THE UNIVERSITY OF LIVERPOOL
Country United Kingdom
Call Details Consolidator Grant (CoG), SH4, ERC-2015-CoG
Summary How children acquire their native language remains one of the key unsolved problems in Cognitive Science. This project will answer a question that lies at the heart of this problem: How do children acquire the abstract generalizations that allow them to produce novel sentences, while avoiding the ungrammatical utterances that result from across-the-board application of these generalizations (e.g., *The clown laughed the man)? Previous single-process theories (the entrenchment, preemption and verb semantics hypotheses) fail to explain all of the current English data, and do not begin to address the issue of how learners of other languages solve this learnability problem. The aim of the present project is to solve this problem by developing and testing a new unified cross-linguistic account of the development of sentence structure. In addition to the overarching theoretical question set out above, the research will address four key questions: (1) What do learners bring to the task in terms of cognitive-semantic universals?; (2) How do children form linguistic generalizations in the first place?; (3) Why are languages the way they are; would other types of systems be difficult or impossible to learn?; (4) What is the nature of development?. These questions will be addressed by means of four Work Packages (WPs). WP1 uses grammaticality judgment and elicited production paradigms developed by the PI to investigate the acquisition of basic transitive and intransitive sentence structure (e.g., The man broke the window/The window broke) across six typologically different languages: English, K’iche’ Mayan, Japanese, Hindi, Hebrew and Turkish (at ages 3-4, 5-6, 9-10 and 18+ years). WP2 uses the same paradigms to investigate idiosyncratic language-specific generalizations within three of these languages. WP3 uses Artificial Grammar Learning to focus on the issue of language evolution. WP4 uses computational modeling to investigate and simulate development.
Summary
How children acquire their native language remains one of the key unsolved problems in Cognitive Science. This project will answer a question that lies at the heart of this problem: How do children acquire the abstract generalizations that allow them to produce novel sentences, while avoiding the ungrammatical utterances that result from across-the-board application of these generalizations (e.g., *The clown laughed the man)? Previous single-process theories (the entrenchment, preemption and verb semantics hypotheses) fail to explain all of the current English data, and do not begin to address the issue of how learners of other languages solve this learnability problem. The aim of the present project is to solve this problem by developing and testing a new unified cross-linguistic account of the development of sentence structure. In addition to the overarching theoretical question set out above, the research will address four key questions: (1) What do learners bring to the task in terms of cognitive-semantic universals?; (2) How do children form linguistic generalizations in the first place?; (3) Why are languages the way they are; would other types of systems be difficult or impossible to learn?; (4) What is the nature of development?. These questions will be addressed by means of four Work Packages (WPs). WP1 uses grammaticality judgment and elicited production paradigms developed by the PI to investigate the acquisition of basic transitive and intransitive sentence structure (e.g., The man broke the window/The window broke) across six typologically different languages: English, K’iche’ Mayan, Japanese, Hindi, Hebrew and Turkish (at ages 3-4, 5-6, 9-10 and 18+ years). WP2 uses the same paradigms to investigate idiosyncratic language-specific generalizations within three of these languages. WP3 uses Artificial Grammar Learning to focus on the issue of language evolution. WP4 uses computational modeling to investigate and simulate development.
Max ERC Funding
1 600 000 €
Duration
Start date: 2016-09-01, End date: 2022-02-28
Project acronym CLIMAHAL
Project Climate dimension of natural halogens in the Earth system: Past, present, future
Researcher (PI) Alfonso SAIZ LOPEZ
Host Institution (HI) AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS
Country Spain
Call Details Consolidator Grant (CoG), PE10, ERC-2016-COG
Summary Naturally-emitted very short-lived halogens (VSLH) have a profound impact on the chemistry and composition of the atmosphere, destroying greenhouse gases and altering aerosol production, which together can change the Earth´s radiative balance. Therefore, natural halogens possess leverage to influence climate, although their contribution to climate change is not well established and most climate models have yet to consider their effects. Also, there is increasing evidence that natural halogens i) impact on the air quality of coastal cities, ii) accelerates the atmospheric deposition of mercury (a toxic heavy metal) and iii) that their natural ocean and ice emissions are controlled by biological and photochemical mechanisms that may respond to climate changes. Motivated by the above, this project aims to quantify the so far unrecognized natural halogen-climate feedbacks and the impact of these feedbacks on global atmospheric oxidizing capacity (AOC) and radiative forcing (RF) across pre-industrial, present and future climates. Answering these questions is essential to predict if these climate-mediated feedbacks can reduce or amplify future climate change. To this end we will develop a multidisciplinary research approach using laboratory and field observations and models interactively that will allow us to peel apart the detailed physical processes behind the contribution of natural halogens to global climate change. Furthermore, the work plan also involves examining past-future climate impacts of natural halogens within a holistic Earth System model, where we will develop the multidirectional halogen interactions in the land-ocean-ice-biosphere-atmosphere coupled system. This will provide a breakthrough in our understanding of the importance of these natural processes for the composition and oxidation capacity of the Earth´s atmosphere and climate, both in the presence and absence of human influence.
Summary
Naturally-emitted very short-lived halogens (VSLH) have a profound impact on the chemistry and composition of the atmosphere, destroying greenhouse gases and altering aerosol production, which together can change the Earth´s radiative balance. Therefore, natural halogens possess leverage to influence climate, although their contribution to climate change is not well established and most climate models have yet to consider their effects. Also, there is increasing evidence that natural halogens i) impact on the air quality of coastal cities, ii) accelerates the atmospheric deposition of mercury (a toxic heavy metal) and iii) that their natural ocean and ice emissions are controlled by biological and photochemical mechanisms that may respond to climate changes. Motivated by the above, this project aims to quantify the so far unrecognized natural halogen-climate feedbacks and the impact of these feedbacks on global atmospheric oxidizing capacity (AOC) and radiative forcing (RF) across pre-industrial, present and future climates. Answering these questions is essential to predict if these climate-mediated feedbacks can reduce or amplify future climate change. To this end we will develop a multidisciplinary research approach using laboratory and field observations and models interactively that will allow us to peel apart the detailed physical processes behind the contribution of natural halogens to global climate change. Furthermore, the work plan also involves examining past-future climate impacts of natural halogens within a holistic Earth System model, where we will develop the multidirectional halogen interactions in the land-ocean-ice-biosphere-atmosphere coupled system. This will provide a breakthrough in our understanding of the importance of these natural processes for the composition and oxidation capacity of the Earth´s atmosphere and climate, both in the presence and absence of human influence.
Max ERC Funding
1 979 112 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym Clock Mechanics
Project Mechanosensation and the circadian clock: a reciprocal analysis
Researcher (PI) Joerg Albert
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Country United Kingdom
Call Details Consolidator Grant (CoG), LS5, ERC-2014-CoG
Summary All forms of life adjust themselves to the daily rhythms of their environments using endogenous oscillators collectively referred to as circadian clocks. Peripheral and central body clocks exist, which both require extrinsic information (e.g. light or temperature changes) to keep in sync with the geophysical cycle (entrainment). In addition, intrinsic cues (e.g. activity levels) have been linked to clock entrainment. Recently, we could show that activation of proprioceptors is sufficient to entrain the central clock of the fruit fly Drosophila melanogaster. Proprioceptors are mechanosensors that monitor the positions, and relative movements, of an animal’s own body parts. The existence of proprioceptive entrainment pathways has significant implications; it implies that an animal’s ‘clock time’ is computed by integrating, and weighting, various external and internal conditions, suggesting the existence of external and internal time.
Using Drosophila, I will investigate the relationship between mechanosensory and circadian systems in a dual, and bidirectional, approach. The project’s first aim is to dissect the neurobiological bases of proprioceptive clock entrainment (i) identifying the specific stimulus requirements for effective entrainment, (ii) determining its mechanosensory pathways and, in a combined computational and experimental strategy, (iii) quantifying the precise contributions of an animal’s activity to its sense of time. The project’s second aim, in turn, is to unravel the roles of the clock, and clock genes, for the function of mechanosensory systems. Previous studies have linked the clock to noise vulnerability in mammalian ears, and clock genes to regeneration in avian ears. Our own preliminary data reveal severe mechanosensory defects in flies mutant for core clock genes. I will use the Drosophila ear as a unifying model to analyse the specific roles of the clock, and clock genes, for the function of mechanotransducer systems.
Summary
All forms of life adjust themselves to the daily rhythms of their environments using endogenous oscillators collectively referred to as circadian clocks. Peripheral and central body clocks exist, which both require extrinsic information (e.g. light or temperature changes) to keep in sync with the geophysical cycle (entrainment). In addition, intrinsic cues (e.g. activity levels) have been linked to clock entrainment. Recently, we could show that activation of proprioceptors is sufficient to entrain the central clock of the fruit fly Drosophila melanogaster. Proprioceptors are mechanosensors that monitor the positions, and relative movements, of an animal’s own body parts. The existence of proprioceptive entrainment pathways has significant implications; it implies that an animal’s ‘clock time’ is computed by integrating, and weighting, various external and internal conditions, suggesting the existence of external and internal time.
Using Drosophila, I will investigate the relationship between mechanosensory and circadian systems in a dual, and bidirectional, approach. The project’s first aim is to dissect the neurobiological bases of proprioceptive clock entrainment (i) identifying the specific stimulus requirements for effective entrainment, (ii) determining its mechanosensory pathways and, in a combined computational and experimental strategy, (iii) quantifying the precise contributions of an animal’s activity to its sense of time. The project’s second aim, in turn, is to unravel the roles of the clock, and clock genes, for the function of mechanosensory systems. Previous studies have linked the clock to noise vulnerability in mammalian ears, and clock genes to regeneration in avian ears. Our own preliminary data reveal severe mechanosensory defects in flies mutant for core clock genes. I will use the Drosophila ear as a unifying model to analyse the specific roles of the clock, and clock genes, for the function of mechanotransducer systems.
Max ERC Funding
1 899 549 €
Duration
Start date: 2015-09-01, End date: 2022-02-28
Project acronym Code4Memory
Project Neural oscillations - a code for memory
Researcher (PI) Simon Hanslmayr
Host Institution (HI) UNIVERSITY OF GLASGOW
Country United Kingdom
Call Details Consolidator Grant (CoG), SH4, ERC-2014-CoG
Summary Episodic memory refers to the fascinating human ability to remember past events in a highly associative and information rich way. But how are these memories coded in human brains? Any mechanism accounting for episodic memory must accomplish at least two functions: to build novel associations, and to represent the information constituting the memory. Neural oscillations, regulating the synchrony of neural assemblies, are ideally suited to accomplish these two functions, but in opposing ways. On the one hand, neurophysiological work suggests that increased synchrony strengthens synaptic connections and thus forms the basis for associative memory. Neurocomputational work, on the other hand, suggests that decreased synchrony is necessary to flexibly express information rich patterns in a neural assembly. Therefore, a conundrum exists as to how oscillations code episodic memory. The aim of this project is to propose and test a new framework that has the potential to reconcile this conflict. The central idea is that synchronization and desynchronization cooperatively code episodic memories, with synchronized activity in the hippocampus in the theta (~4 Hz) and gamma (~ 40-60 Hz) frequency range mediating the building of associations, and neocortical desynchronization in the alpha (~10 Hz) and beta (~15 Hz) frequency range mediating the representation of mnemonic information. Importantly the two modules, with their respective synchronous/asynchronous behaviours, must interact during the formation and retrieval of episodic memories, but how and whether this is the case remains untested to date. I will test these fundamental questions using a multidisciplinary and multi-method approach, including human single cell recordings, neuroimaging, brain stimulation, and computational modelling. The results from these experiments have the potential to reveal the neural code that human episodic memory is based on, which is still one of the biggest mysteries of the human mind.
Summary
Episodic memory refers to the fascinating human ability to remember past events in a highly associative and information rich way. But how are these memories coded in human brains? Any mechanism accounting for episodic memory must accomplish at least two functions: to build novel associations, and to represent the information constituting the memory. Neural oscillations, regulating the synchrony of neural assemblies, are ideally suited to accomplish these two functions, but in opposing ways. On the one hand, neurophysiological work suggests that increased synchrony strengthens synaptic connections and thus forms the basis for associative memory. Neurocomputational work, on the other hand, suggests that decreased synchrony is necessary to flexibly express information rich patterns in a neural assembly. Therefore, a conundrum exists as to how oscillations code episodic memory. The aim of this project is to propose and test a new framework that has the potential to reconcile this conflict. The central idea is that synchronization and desynchronization cooperatively code episodic memories, with synchronized activity in the hippocampus in the theta (~4 Hz) and gamma (~ 40-60 Hz) frequency range mediating the building of associations, and neocortical desynchronization in the alpha (~10 Hz) and beta (~15 Hz) frequency range mediating the representation of mnemonic information. Importantly the two modules, with their respective synchronous/asynchronous behaviours, must interact during the formation and retrieval of episodic memories, but how and whether this is the case remains untested to date. I will test these fundamental questions using a multidisciplinary and multi-method approach, including human single cell recordings, neuroimaging, brain stimulation, and computational modelling. The results from these experiments have the potential to reveal the neural code that human episodic memory is based on, which is still one of the biggest mysteries of the human mind.
Max ERC Funding
1 897 751 €
Duration
Start date: 2015-10-01, End date: 2021-09-30
