Project acronym AGENSI
Project A Genetic View into Past Sea Ice Variability in the Arctic
Researcher (PI) Stijn DE SCHEPPER
Host Institution (HI) NORCE NORWEGIAN RESEARCH CENTRE AS
Call Details Consolidator Grant (CoG), PE10, ERC-2018-COG
Summary Arctic sea ice decline is the exponent of the rapidly transforming Arctic climate. The ensuing local and global implications can be understood by studying past climate transitions, yet few methods are available to examine past Arctic sea ice cover, severely restricting our understanding of sea ice in the climate system. The decline in Arctic sea ice cover is a ‘canary in the coalmine’ for the state of our climate, and if greenhouse gas emissions remain unchecked, summer sea ice loss may pass a critical threshold that could drastically transform the Arctic. Because historical observations are limited, it is crucial to have reliable proxies for assessing natural sea ice variability, its stability and sensitivity to climate forcing on different time scales. Current proxies address aspects of sea ice variability, but are limited due to a selective fossil record, preservation effects, regional applicability, or being semi-quantitative. With such restraints on our knowledge about natural variations and drivers, major uncertainties about the future remain.
I propose to develop and apply a novel sea ice proxy that exploits genetic information stored in marine sediments, sedimentary ancient DNA (sedaDNA). This innovation uses the genetic signature of phytoplankton communities from surface waters and sea ice as it gets stored in sediments. This wealth of information has not been explored before for reconstructing sea ice conditions. Preliminary results from my cross-disciplinary team indicate that our unconventional approach can provide a detailed, qualitative account of past sea ice ecosystems and quantitative estimates of sea ice parameters. I will address fundamental questions about past Arctic sea ice variability on different timescales, information essential to provide a framework upon which to assess the ecological and socio-economic consequences of a changing Arctic. This new proxy is not limited to sea ice research and can transform the field of paleoceanography.
Summary
Arctic sea ice decline is the exponent of the rapidly transforming Arctic climate. The ensuing local and global implications can be understood by studying past climate transitions, yet few methods are available to examine past Arctic sea ice cover, severely restricting our understanding of sea ice in the climate system. The decline in Arctic sea ice cover is a ‘canary in the coalmine’ for the state of our climate, and if greenhouse gas emissions remain unchecked, summer sea ice loss may pass a critical threshold that could drastically transform the Arctic. Because historical observations are limited, it is crucial to have reliable proxies for assessing natural sea ice variability, its stability and sensitivity to climate forcing on different time scales. Current proxies address aspects of sea ice variability, but are limited due to a selective fossil record, preservation effects, regional applicability, or being semi-quantitative. With such restraints on our knowledge about natural variations and drivers, major uncertainties about the future remain.
I propose to develop and apply a novel sea ice proxy that exploits genetic information stored in marine sediments, sedimentary ancient DNA (sedaDNA). This innovation uses the genetic signature of phytoplankton communities from surface waters and sea ice as it gets stored in sediments. This wealth of information has not been explored before for reconstructing sea ice conditions. Preliminary results from my cross-disciplinary team indicate that our unconventional approach can provide a detailed, qualitative account of past sea ice ecosystems and quantitative estimates of sea ice parameters. I will address fundamental questions about past Arctic sea ice variability on different timescales, information essential to provide a framework upon which to assess the ecological and socio-economic consequences of a changing Arctic. This new proxy is not limited to sea ice research and can transform the field of paleoceanography.
Max ERC Funding
2 615 858 €
Duration
Start date: 2019-08-01, End date: 2024-07-31
Project acronym ARCHEIS
Project Understanding the onset and impact of Aquatic Resource Consumption in Human Evolution using novel Isotopic tracerS
Researcher (PI) Klervia Marie Madalen JAOUEN
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE10, ERC-2018-STG
Summary The onset of the systematic consumption of marine resources is thought to mark a turning point for the hominin lineage. To date, this onset cannot be traced, since classic isotope markers are not preserved beyond 50 - 100 ky. Aquatic food products are essential in human nutrition as the main source of polyunsaturated fatty acids in hunter-gatherer diets. The exploitation of marine resources is also thought to have reduced human mobility and enhanced social and technological complexification. Systematic aquatic food consumption could well have been a distinctive feature of Homo sapiens species among his fellow hominins, and has been linked to the astonishing leap in human intelligence and conscience. Yet, this hypothesis is challenged by the existence of mollusk and marine mammal bone remains at Neanderthal archeological sites. Recent work demonstrated the sensitivity of Zn isotope composition in bioapatite, the mineral part of bones and teeth, to dietary Zn. By combining classic (C and C/N isotope analyses) and innovative techniques (compound specific C/N and bulk Zn isotope analyses), I will develop a suite of sensitive tracers for shellfish, fish and marine mammal consumption. Shellfish consumption will be investigated by comparing various South American and European prehistoric populations from the Atlantic coast associated to shell-midden and fish-mounds. Marine mammal consumption will be traced using an Inuit population of Arctic Canada and the Wairau Bar population of New Zealand. C/N/Zn isotope compositions of various aquatic products will also be assessed, as well as isotope fractionation during intestinal absorption. I will then use the fully calibrated isotope tools to detect and characterize the onset of marine food exploitation in human history, which will answer the question of its specificity to our species. Neanderthal, early modern humans and possibly other hominin remains from coastal and inland sites will be compared in that purpose.
Summary
The onset of the systematic consumption of marine resources is thought to mark a turning point for the hominin lineage. To date, this onset cannot be traced, since classic isotope markers are not preserved beyond 50 - 100 ky. Aquatic food products are essential in human nutrition as the main source of polyunsaturated fatty acids in hunter-gatherer diets. The exploitation of marine resources is also thought to have reduced human mobility and enhanced social and technological complexification. Systematic aquatic food consumption could well have been a distinctive feature of Homo sapiens species among his fellow hominins, and has been linked to the astonishing leap in human intelligence and conscience. Yet, this hypothesis is challenged by the existence of mollusk and marine mammal bone remains at Neanderthal archeological sites. Recent work demonstrated the sensitivity of Zn isotope composition in bioapatite, the mineral part of bones and teeth, to dietary Zn. By combining classic (C and C/N isotope analyses) and innovative techniques (compound specific C/N and bulk Zn isotope analyses), I will develop a suite of sensitive tracers for shellfish, fish and marine mammal consumption. Shellfish consumption will be investigated by comparing various South American and European prehistoric populations from the Atlantic coast associated to shell-midden and fish-mounds. Marine mammal consumption will be traced using an Inuit population of Arctic Canada and the Wairau Bar population of New Zealand. C/N/Zn isotope compositions of various aquatic products will also be assessed, as well as isotope fractionation during intestinal absorption. I will then use the fully calibrated isotope tools to detect and characterize the onset of marine food exploitation in human history, which will answer the question of its specificity to our species. Neanderthal, early modern humans and possibly other hominin remains from coastal and inland sites will be compared in that purpose.
Max ERC Funding
1 361 991 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym ARGO
Project The Quest of the Argonautes - from Myth to Reality
Researcher (PI) JOHN VAN DER OOST
Host Institution (HI) WAGENINGEN UNIVERSITY
Call Details Advanced Grant (AdG), LS1, ERC-2018-ADG
Summary Argonaute nucleases are key players of the eukaryotic RNA interference (RNAi) system. Using small RNA guides, these Argonaute (Ago) proteins specifically target complementary RNA molecules, resulting in regulation of a wide range of crucial processes, including chromosome organization, gene expression and anti-virus defence. Since 2010, my research team has studied closely-related prokaryotic Argonaute (pAgo) variants. This has revealed spectacular mechanistic variations: several thermophilic pAgos catalyse DNA-guided cleavage of double stranded DNA, but only at elevated temperatures. Interestingly, a recently discovered mesophilic Argonaute (CbAgo) can generate double strand DNA breaks at moderate temperatures, providing an excellent basis for this ARGO project. In addition, genome analysis has revealed many distantly-related Argonaute variants, often with unique domain architectures. Hence, the currently known Argonaute homologs are just the tip of the iceberg, and the stage is set for making a big leap in the exploration of the Argonaute family. Initially we will dissect the molecular basis of functional and mechanistic features of uncharacterized natural Argonaute variants, both in eukaryotes (the presence of an Ago-like subunit in the Mediator complex, strongly suggests a regulatory role of an elusive non-coding RNA ligand) and in prokaryotes (selected Ago variants possess distinct domains indicating novel functionalities). After their thorough biochemical characterization, I aim at engineering the functionality of the aforementioned CbAgo through an integrated rational & random approach, i.e. by tinkering of domains, and by an unprecedented in vitro laboratory evolution approach. Eventually, natural & synthetic Argonautes will be selected for their exploitation, and used for developing original genome editing applications (from silencing to base editing). Embarking on this ambitious ARGO expedition will lead us to many exciting discoveries.
Summary
Argonaute nucleases are key players of the eukaryotic RNA interference (RNAi) system. Using small RNA guides, these Argonaute (Ago) proteins specifically target complementary RNA molecules, resulting in regulation of a wide range of crucial processes, including chromosome organization, gene expression and anti-virus defence. Since 2010, my research team has studied closely-related prokaryotic Argonaute (pAgo) variants. This has revealed spectacular mechanistic variations: several thermophilic pAgos catalyse DNA-guided cleavage of double stranded DNA, but only at elevated temperatures. Interestingly, a recently discovered mesophilic Argonaute (CbAgo) can generate double strand DNA breaks at moderate temperatures, providing an excellent basis for this ARGO project. In addition, genome analysis has revealed many distantly-related Argonaute variants, often with unique domain architectures. Hence, the currently known Argonaute homologs are just the tip of the iceberg, and the stage is set for making a big leap in the exploration of the Argonaute family. Initially we will dissect the molecular basis of functional and mechanistic features of uncharacterized natural Argonaute variants, both in eukaryotes (the presence of an Ago-like subunit in the Mediator complex, strongly suggests a regulatory role of an elusive non-coding RNA ligand) and in prokaryotes (selected Ago variants possess distinct domains indicating novel functionalities). After their thorough biochemical characterization, I aim at engineering the functionality of the aforementioned CbAgo through an integrated rational & random approach, i.e. by tinkering of domains, and by an unprecedented in vitro laboratory evolution approach. Eventually, natural & synthetic Argonautes will be selected for their exploitation, and used for developing original genome editing applications (from silencing to base editing). Embarking on this ambitious ARGO expedition will lead us to many exciting discoveries.
Max ERC Funding
2 177 158 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym BrokenGenome
Project Breaking and rebuilding the genome: mechanistic rules for the dangerous game of sex.
Researcher (PI) Corentin CLAEYS BOUUAERT
Host Institution (HI) UNIVERSITE CATHOLIQUE DE LOUVAIN
Call Details Starting Grant (StG), LS1, ERC-2018-STG
Summary Sexual reproduction depends on the programmed induction of DNA double-strand breaks (DSBs) and their ensuing repair by homologous recombination. This complex process is essential for sexual reproduction because it ultimately allows the pairing and separation of homologous chromosomes during formation of haploid gametes. Although meiotic recombination has been investigated for decades, many of the underlying molecular processes remain unclear, largely due to the lack of biochemical studies. I have recently made important progress by, for the first time, successfully purifying proteins involved in two aspects of meiotic recombination: DSB formation and the final stage of formation of the crossovers that are a central raison-d’être of meiotic recombination. This has opened new avenues for future research that I intend to pursue in my own laboratory. Here, I propose a set of biochemical approaches, complemented by molecular genetics methods, to gain insights into four central problems: (i) How meiotic proteins collaborate to induce DSBs; (ii) How DSB proteins interact with components that form the axes of meiotic chromosomes; (iii) How proteins involved at later stages of recombination form crossovers; and (iv) How crossover proteins interact with components of synapsed chromosomes. For each problem, I will set up in vitro systems to probe the activities of the players involved, their interactions with DNA, and their assembly into macromolecular complexes. In addition, I propose to develop new methodology for identifying proteins that are associated with DNA that has undergone recombination-related DNA synthesis. My goal is to gain insights into the mechanisms that govern meiotic recombination. Importantly, these mechanisms are intimately linked not only to gamete formation, but also to the general recombination pathways that all cells use to maintain genome stability. In both contexts, our findings will be relevant to the development and avoidance of disease states.
Summary
Sexual reproduction depends on the programmed induction of DNA double-strand breaks (DSBs) and their ensuing repair by homologous recombination. This complex process is essential for sexual reproduction because it ultimately allows the pairing and separation of homologous chromosomes during formation of haploid gametes. Although meiotic recombination has been investigated for decades, many of the underlying molecular processes remain unclear, largely due to the lack of biochemical studies. I have recently made important progress by, for the first time, successfully purifying proteins involved in two aspects of meiotic recombination: DSB formation and the final stage of formation of the crossovers that are a central raison-d’être of meiotic recombination. This has opened new avenues for future research that I intend to pursue in my own laboratory. Here, I propose a set of biochemical approaches, complemented by molecular genetics methods, to gain insights into four central problems: (i) How meiotic proteins collaborate to induce DSBs; (ii) How DSB proteins interact with components that form the axes of meiotic chromosomes; (iii) How proteins involved at later stages of recombination form crossovers; and (iv) How crossover proteins interact with components of synapsed chromosomes. For each problem, I will set up in vitro systems to probe the activities of the players involved, their interactions with DNA, and their assembly into macromolecular complexes. In addition, I propose to develop new methodology for identifying proteins that are associated with DNA that has undergone recombination-related DNA synthesis. My goal is to gain insights into the mechanisms that govern meiotic recombination. Importantly, these mechanisms are intimately linked not only to gamete formation, but also to the general recombination pathways that all cells use to maintain genome stability. In both contexts, our findings will be relevant to the development and avoidance of disease states.
Max ERC Funding
1 499 075 €
Duration
Start date: 2019-07-01, End date: 2024-06-30
Project acronym CARB-City
Project Physico-Chemistry of Carbonaceous Aerosol Pollution in Evolving Cities
Researcher (PI) Alma Hodzic
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), PE10, ERC-2018-COG
Summary Carbonaceous aerosols (organic and black carbon) remain a major unresolved issue in atmospheric science, especially in urban centers, where they are one of the dominant aerosol constituents and among most toxic to human health. The challenge is twofold: first, our understanding of the sources, sinks and physico-chemical properties of the complex mixture of carbonaceous species is still incomplete; and second, the representation of urban heterogeneities in air quality models is inadequate as they are designed for regional applications.
The CARB-City project proposes the development of an innovative modeling framework that will address both issues by combining molecular-level chemical constraints and city-scale modeling to achieve the following objectives: (WP1) to develop and apply new chemical parameterizations, constrained by an explicit chemical model, for carbonaceous aerosol formation from urban precursors, and (WP2) to examine whether urban heterogeneities in sources and mixing can enhance non-linearities in chemistry of carbonaceous compounds and modify their predicted composition. The new modeling framework will then be applied (WP3) to quantify the contribution of traditional and emerging urban aerosol precursor sources to chemistry and toxicity of carbonaceous aerosols; and (WP4) to assess the effectiveness of greener-city strategies in removing aerosol pollutants.
This work will enhance fundamental scientific understanding as to how key physico-chemical processes control the lifecycle of carbonaceous aerosols in cities, and will improve the predictability of air quality models in terms of composition and toxicity of urban aerosols, and their sensitivity to changes in energy and land use that cities are currently experiencing. The modeling framework will have the required chemical and spatial resolution for assessing human exposure to urban aerosols. This will allow policy makers to optimize urban emission reductions and sustainable urban development.
Summary
Carbonaceous aerosols (organic and black carbon) remain a major unresolved issue in atmospheric science, especially in urban centers, where they are one of the dominant aerosol constituents and among most toxic to human health. The challenge is twofold: first, our understanding of the sources, sinks and physico-chemical properties of the complex mixture of carbonaceous species is still incomplete; and second, the representation of urban heterogeneities in air quality models is inadequate as they are designed for regional applications.
The CARB-City project proposes the development of an innovative modeling framework that will address both issues by combining molecular-level chemical constraints and city-scale modeling to achieve the following objectives: (WP1) to develop and apply new chemical parameterizations, constrained by an explicit chemical model, for carbonaceous aerosol formation from urban precursors, and (WP2) to examine whether urban heterogeneities in sources and mixing can enhance non-linearities in chemistry of carbonaceous compounds and modify their predicted composition. The new modeling framework will then be applied (WP3) to quantify the contribution of traditional and emerging urban aerosol precursor sources to chemistry and toxicity of carbonaceous aerosols; and (WP4) to assess the effectiveness of greener-city strategies in removing aerosol pollutants.
This work will enhance fundamental scientific understanding as to how key physico-chemical processes control the lifecycle of carbonaceous aerosols in cities, and will improve the predictability of air quality models in terms of composition and toxicity of urban aerosols, and their sensitivity to changes in energy and land use that cities are currently experiencing. The modeling framework will have the required chemical and spatial resolution for assessing human exposure to urban aerosols. This will allow policy makers to optimize urban emission reductions and sustainable urban development.
Max ERC Funding
1 727 009 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym CASSANDRA
Project Accelerating mass loss of Greenland: firn and the shifting runoff limit
Researcher (PI) Horst MACHGUTH
Host Institution (HI) UNIVERSITE DE FRIBOURG
Call Details Consolidator Grant (CoG), PE10, ERC-2018-COG
Summary Meltwater running off the flanks of the Greenland ice sheet contributes roughly 60% to its mass loss, the rest being due to calving. Only meltwater originating from below the elevation of the runoff limit leaves the ice sheet, contributing to mass loss; melt at higher elevations refreezes in the porous firn and does not drive mass loss. Therefore any shift in the runoff limit modifies mass loss and subsequent sea level rise. New evidence shows surface runoff at increasingly high elevations, outpacing the rate at which the equilibrium line elevation rises. This research proposal focuses on the runoff limit as a powerful yet poorly understood modulator of Greenland mass balance. We will track the runoff limit over the full satellite era using two of the largest and oldest remote sensing archives, Landsat and the Advanced Very High Resolution Radiometer (AVHRR). We will establish time series of the runoff limit for all regions of Greenland to identify the mechanisms driving fluctuations in the runoff limit. This newly gained process understanding and a wealth of in-situ measurements will then be used to build firn hydrology models capable of simulating runoff and the associated runoff limit over time. Eventually, the firn hydrology models will be applied to reconcile estimates of Greenland past, present and future mass balance. Covering the entire satellite era and all of Greenland, the focus on the runoff limit will constitute a paradigm shift leading to major advance in our understanding of how vulnerable the surface of the ice sheet reacts to climate change and how the changing surface impacts runoff and thus Greenland's role in the global sea level budget.
Summary
Meltwater running off the flanks of the Greenland ice sheet contributes roughly 60% to its mass loss, the rest being due to calving. Only meltwater originating from below the elevation of the runoff limit leaves the ice sheet, contributing to mass loss; melt at higher elevations refreezes in the porous firn and does not drive mass loss. Therefore any shift in the runoff limit modifies mass loss and subsequent sea level rise. New evidence shows surface runoff at increasingly high elevations, outpacing the rate at which the equilibrium line elevation rises. This research proposal focuses on the runoff limit as a powerful yet poorly understood modulator of Greenland mass balance. We will track the runoff limit over the full satellite era using two of the largest and oldest remote sensing archives, Landsat and the Advanced Very High Resolution Radiometer (AVHRR). We will establish time series of the runoff limit for all regions of Greenland to identify the mechanisms driving fluctuations in the runoff limit. This newly gained process understanding and a wealth of in-situ measurements will then be used to build firn hydrology models capable of simulating runoff and the associated runoff limit over time. Eventually, the firn hydrology models will be applied to reconcile estimates of Greenland past, present and future mass balance. Covering the entire satellite era and all of Greenland, the focus on the runoff limit will constitute a paradigm shift leading to major advance in our understanding of how vulnerable the surface of the ice sheet reacts to climate change and how the changing surface impacts runoff and thus Greenland's role in the global sea level budget.
Max ERC Funding
1 989 181 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym CiliaTubulinCode
Project Self-organization of the cilium: the role of the tubulin code
Researcher (PI) Gaia PIGINO
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Consolidator Grant (CoG), LS1, ERC-2018-COG
Summary This project aims at understanding of the role of the tubulin code for self-organization of complex microtubule based structures. Cilia turn out to be the ideal structures for the proposed research.
A cilium is a sophisticated cellular machine that self-organizes from many protein complexes. It plays motility, sensory, and signaling roles in most eukaryotic cells, and its malfunction causes pathologies. The assembly of the cilium requires intraflagellar transport (IFT), a specialized bidirectional motility process that is mediated by adaptor proteins and direction specific molecular motors. Work from my lab shows that anterograde and retrograde IFT make exclusive use of the B-tubules and A-tubules, respectively. This insight answered a long standing question and shows that functional differentiation of tubules exists and is important for IFT.
Tubulin post-translational modifications (PTMs) contribute to a tubulin code, making microtubules suitable for specific functions. Mutation of tubulin-PTM enzymes can have dramatic effects on cilia function and assembly. However, we do not understand of the role of tubulin-PTMs in cilia. Therefore, I propose to address the hypotheses that the tubulin code contributes to regulating bidirectional IFT motility, and more generally, that the tubulin code is a key player in structuring complex cellular assembly processes in space and time.
This proposal aims at (i) understanding if tubulin-PTMs are necessary and/or sufficient to regulate the bidirectionality of IFT (ii) examining how the tubulin code regulates the assembly of cilia and (iii) generating a high-resolution atlas of tubulin-PTMs and their respective enzymes.
We will combine advanced techniques encompassing state-of-the-art cryo-electron tomography, biochemical imaging, fluorescent microscopy, and in vitro assays to achieve molecular and structural understanding of the role of the tubulin code in the self-organization of cilia and of microtubule based cellular structures.
Summary
This project aims at understanding of the role of the tubulin code for self-organization of complex microtubule based structures. Cilia turn out to be the ideal structures for the proposed research.
A cilium is a sophisticated cellular machine that self-organizes from many protein complexes. It plays motility, sensory, and signaling roles in most eukaryotic cells, and its malfunction causes pathologies. The assembly of the cilium requires intraflagellar transport (IFT), a specialized bidirectional motility process that is mediated by adaptor proteins and direction specific molecular motors. Work from my lab shows that anterograde and retrograde IFT make exclusive use of the B-tubules and A-tubules, respectively. This insight answered a long standing question and shows that functional differentiation of tubules exists and is important for IFT.
Tubulin post-translational modifications (PTMs) contribute to a tubulin code, making microtubules suitable for specific functions. Mutation of tubulin-PTM enzymes can have dramatic effects on cilia function and assembly. However, we do not understand of the role of tubulin-PTMs in cilia. Therefore, I propose to address the hypotheses that the tubulin code contributes to regulating bidirectional IFT motility, and more generally, that the tubulin code is a key player in structuring complex cellular assembly processes in space and time.
This proposal aims at (i) understanding if tubulin-PTMs are necessary and/or sufficient to regulate the bidirectionality of IFT (ii) examining how the tubulin code regulates the assembly of cilia and (iii) generating a high-resolution atlas of tubulin-PTMs and their respective enzymes.
We will combine advanced techniques encompassing state-of-the-art cryo-electron tomography, biochemical imaging, fluorescent microscopy, and in vitro assays to achieve molecular and structural understanding of the role of the tubulin code in the self-organization of cilia and of microtubule based cellular structures.
Max ERC Funding
1 986 406 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
Project acronym CLUSTER
Project organisation of CLoUdS, and implications for Tropical cyclones and for the Energetics of the tropics, in current and in a waRming climate
Researcher (PI) caroline MULLER
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Starting Grant (StG), PE10, ERC-2018-STG
Summary Few geophysical phenomena are as spectacular as tropical cyclones, with their eye surrounded by sharp cloudy eyewalls. There are other types of spatially organised convection (convection refers to overturning of air within which clouds are embedded), in fact organised convection is ubiquitous in the tropics. But it is still poorly understood and poorly represented in convective parameterisations of global climate models, despite its strong societal and climatic impact. It is associated with extreme weather, and with dramatic changes of the large scales, including drying of the atmosphere and increased outgoing longwave radiation to space. The latter can have dramatic consequences on tropical energetics, and hence on global climate. Thus, convective organisation could be a key missing ingredient in current estimates of climate sensitivity from climate models.
CLUSTER will lead to improved fundamental understanding of convective organisation to help guide and improve convective parameterisations. It is closely related to the World Climate Research Programme (WCRP) grand challenge: Clouds, circulation and climate sensitivity. Grand challenges identify areas of emphasis in the coming decade, targeting specific barriers preventing progress in critical areas of climate science.
Until recently, progress on this topic was hindered by high numerical cost and lack of fundamental understanding. Advances in computer power combined with new discoveries based on idealised frameworks, theory and observational findings, make this the ideal time to determine the fundamental processes governing convective organisation in nature. Using a synergy of theory, high-resolution cloud-resolving simulations, and in-situ and satellite observations, CLUSTER will specifically target two feedbacks recently identified as being essential to convective aggregation, and assess their impact on tropical cyclones, large-scale properties including precipitation extremes, and energetics of the tropics.
Summary
Few geophysical phenomena are as spectacular as tropical cyclones, with their eye surrounded by sharp cloudy eyewalls. There are other types of spatially organised convection (convection refers to overturning of air within which clouds are embedded), in fact organised convection is ubiquitous in the tropics. But it is still poorly understood and poorly represented in convective parameterisations of global climate models, despite its strong societal and climatic impact. It is associated with extreme weather, and with dramatic changes of the large scales, including drying of the atmosphere and increased outgoing longwave radiation to space. The latter can have dramatic consequences on tropical energetics, and hence on global climate. Thus, convective organisation could be a key missing ingredient in current estimates of climate sensitivity from climate models.
CLUSTER will lead to improved fundamental understanding of convective organisation to help guide and improve convective parameterisations. It is closely related to the World Climate Research Programme (WCRP) grand challenge: Clouds, circulation and climate sensitivity. Grand challenges identify areas of emphasis in the coming decade, targeting specific barriers preventing progress in critical areas of climate science.
Until recently, progress on this topic was hindered by high numerical cost and lack of fundamental understanding. Advances in computer power combined with new discoveries based on idealised frameworks, theory and observational findings, make this the ideal time to determine the fundamental processes governing convective organisation in nature. Using a synergy of theory, high-resolution cloud-resolving simulations, and in-situ and satellite observations, CLUSTER will specifically target two feedbacks recently identified as being essential to convective aggregation, and assess their impact on tropical cyclones, large-scale properties including precipitation extremes, and energetics of the tropics.
Max ERC Funding
1 078 021 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym CRISPR2.0
Project Microbial genome defence pathways: from molecular mechanisms to next-generation molecular tools
Researcher (PI) Martin JINEK
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Consolidator Grant (CoG), LS1, ERC-2018-COG
Summary The constant arms race between prokaryotic microbes and their molecular parasites such as viruses, plasmids and transposons has driven the evolution of complex genome defence mechanisms. The CRISPR-Cas defence systems provide adaptive RNA-guided immunity against invasive nucleic acid elements. CRISPR-associated effector nucleases such as Cas9, Cas12a and Cas13 have emerged as powerful tools for precision genome editing, gene expression control and nucleic acid detection. However, these technologies suffer from drawbacks that limit their efficacy and versatility, necessitating the search for additional exploitable molecular activities. Building on our recent structural and biochemical studies, the goal of this project is to investigate the molecular architectures and mechanisms of CRISPR-associated systems and other genome defence mechanisms, aiming not only to shed light on their biological roles but also inform their technological development. Specifically, the proposed studies will examine (i) the molecular basis of cyclic oligoadenylate signalling in type III CRISPR-Cas systems, (ii) the mechanism of transposon-associated type I CRISPR-Cas systems and their putative function in RNA-guided DNA transposition, and (iii) molecular activities associated with recently described non-CRISPR defence systems. Collectively, the proposed studies will advance our understanding of the molecular functions of genome defence mechanisms in shaping the evolution of prokaryotic genomes and make critical contributions to their development as novel genetic engineering tools.
Summary
The constant arms race between prokaryotic microbes and their molecular parasites such as viruses, plasmids and transposons has driven the evolution of complex genome defence mechanisms. The CRISPR-Cas defence systems provide adaptive RNA-guided immunity against invasive nucleic acid elements. CRISPR-associated effector nucleases such as Cas9, Cas12a and Cas13 have emerged as powerful tools for precision genome editing, gene expression control and nucleic acid detection. However, these technologies suffer from drawbacks that limit their efficacy and versatility, necessitating the search for additional exploitable molecular activities. Building on our recent structural and biochemical studies, the goal of this project is to investigate the molecular architectures and mechanisms of CRISPR-associated systems and other genome defence mechanisms, aiming not only to shed light on their biological roles but also inform their technological development. Specifically, the proposed studies will examine (i) the molecular basis of cyclic oligoadenylate signalling in type III CRISPR-Cas systems, (ii) the mechanism of transposon-associated type I CRISPR-Cas systems and their putative function in RNA-guided DNA transposition, and (iii) molecular activities associated with recently described non-CRISPR defence systems. Collectively, the proposed studies will advance our understanding of the molecular functions of genome defence mechanisms in shaping the evolution of prokaryotic genomes and make critical contributions to their development as novel genetic engineering tools.
Max ERC Funding
1 996 525 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
Project acronym CRYOREP
Project Chromosome Replication Visualised by Cryo-EM
Researcher (PI) Alessandro COSTA
Host Institution (HI) THE FRANCIS CRICK INSTITUTE LIMITED
Call Details Consolidator Grant (CoG), LS1, ERC-2018-COG
Summary In eukaryotic cells, DNA replication is tightly regulated to ensure that the genome is duplicated only once per cell cycle. Errors in the control mechanisms that regulate chromosome ploidy cause genomic instability, which is linked to the development of cellular abnormalities, genetic disease and the onset of cancer. Recent reconstitution experiments performed with purified proteins revealed that initiation of eukaryotic genome duplication requires three distinct steps. First, DNA replication start sites are identified and targeted for the loading of an inactive MCM helicase motor, which encircles the double helix. Second, MCM activators are recruited, causing duplex-DNA untwisting. Third, upon interaction with a firing factor, the MCM ring opens to eject one DNA strand, leading to unwinding of the replication fork and duplication by dedicated replicative polymerases. These three events are not understood at a molecular level. Structural investigations so far aimed at imaging artificially isolated replication steps and used simplified templates, such as linear duplex DNA to study helicase loading or pre-formed forks to understand unwinding. However, the natural substrate of the eukaryotic replication machinery is not DNA but rather chromatin, formed of nucleosome arrays that compact the genome. Chromatin plays important regulatory roles in all steps of DNA replication, by dictating origin start-site selection and stimulating replication fork progression. Only by studying chromatin replication, we argue, will we understand the molecular basis of genome propagation. To this end, we have developed new protocols to perform visual biochemistry experiments under the cryo-electron microscope, to image chromatin duplication at high resolution, frozen as it is being catalysed. Using these strategies we want to generate a molecular movie of the entire replication reaction. Our achievements will change the way we think about genome stability in eukaryotic cells.
Summary
In eukaryotic cells, DNA replication is tightly regulated to ensure that the genome is duplicated only once per cell cycle. Errors in the control mechanisms that regulate chromosome ploidy cause genomic instability, which is linked to the development of cellular abnormalities, genetic disease and the onset of cancer. Recent reconstitution experiments performed with purified proteins revealed that initiation of eukaryotic genome duplication requires three distinct steps. First, DNA replication start sites are identified and targeted for the loading of an inactive MCM helicase motor, which encircles the double helix. Second, MCM activators are recruited, causing duplex-DNA untwisting. Third, upon interaction with a firing factor, the MCM ring opens to eject one DNA strand, leading to unwinding of the replication fork and duplication by dedicated replicative polymerases. These three events are not understood at a molecular level. Structural investigations so far aimed at imaging artificially isolated replication steps and used simplified templates, such as linear duplex DNA to study helicase loading or pre-formed forks to understand unwinding. However, the natural substrate of the eukaryotic replication machinery is not DNA but rather chromatin, formed of nucleosome arrays that compact the genome. Chromatin plays important regulatory roles in all steps of DNA replication, by dictating origin start-site selection and stimulating replication fork progression. Only by studying chromatin replication, we argue, will we understand the molecular basis of genome propagation. To this end, we have developed new protocols to perform visual biochemistry experiments under the cryo-electron microscope, to image chromatin duplication at high resolution, frozen as it is being catalysed. Using these strategies we want to generate a molecular movie of the entire replication reaction. Our achievements will change the way we think about genome stability in eukaryotic cells.
Max ERC Funding
2 000 000 €
Duration
Start date: 2019-03-01, End date: 2024-02-29
