Project acronym CELLFUSION
Project Molecular dissection of the mechanisms of cell-cell fusion in the fission yeast
Researcher (PI) Sophie Geneviève Elisabeth Martin Benton
Host Institution (HI) UNIVERSITE DE LAUSANNE
Call Details Consolidator Grant (CoG), LS3, ERC-2015-CoG
Summary Cell fusion is critical for fertilization and development, for instance underlying muscle or bone formation. Cell fusion may also play important roles in regeneration and cancer. A conceptual understanding is emerging that cell fusion requires cell-cell communication, polarization of the cells towards each other, and assembly of a fusion machinery, in which an actin-based structure promotes membrane juxtaposition and fusogenic factors drive membrane fusion. However, in no single system have the molecular nature of all these parts been described, and thus the molecular basis of cell fusion remains poorly understood.
This proposal aims to depict the complete fusion process in a single organism, using the simple yeast model Schizosaccharomyces pombe, which has a long track record of discoveries in fundamental cellular processes. These haploid cells, which fuse to generate a diploid zygote, use highly conserved mechanisms of cell-cell communication (through pheromones and GPCR signaling), cell polarization (centred around the small GTPase Cdc42) and fusion. Indeed, we recently showed that these cells assemble an actin-based fusion structure, dubbed the actin fusion focus. Our five aims probe the molecular nature of, and the links between, signaling, polarization and the fusion machinery from initiation to termination of the process. These are:
1: To define the roles and feedback regulation of Cdc42 during cell fusion
2: To understand the molecular mechanisms of actin fusion focus formation
3: To identify the fusogen(s) promoting membrane fusion
4: To probe the GPCR signal for fusion initiation
5: To define the mechanism of fusion termination
By combining genetic, optogenetic, biochemical, live-imaging, synthetic and modeling approaches, this project will bring a molecular and conceptual understanding of cell fusion. This work will have far-ranging relevance for cell polarization, cytoskeletal organization, cell signalling and communication, and cell fate regulation.
Summary
Cell fusion is critical for fertilization and development, for instance underlying muscle or bone formation. Cell fusion may also play important roles in regeneration and cancer. A conceptual understanding is emerging that cell fusion requires cell-cell communication, polarization of the cells towards each other, and assembly of a fusion machinery, in which an actin-based structure promotes membrane juxtaposition and fusogenic factors drive membrane fusion. However, in no single system have the molecular nature of all these parts been described, and thus the molecular basis of cell fusion remains poorly understood.
This proposal aims to depict the complete fusion process in a single organism, using the simple yeast model Schizosaccharomyces pombe, which has a long track record of discoveries in fundamental cellular processes. These haploid cells, which fuse to generate a diploid zygote, use highly conserved mechanisms of cell-cell communication (through pheromones and GPCR signaling), cell polarization (centred around the small GTPase Cdc42) and fusion. Indeed, we recently showed that these cells assemble an actin-based fusion structure, dubbed the actin fusion focus. Our five aims probe the molecular nature of, and the links between, signaling, polarization and the fusion machinery from initiation to termination of the process. These are:
1: To define the roles and feedback regulation of Cdc42 during cell fusion
2: To understand the molecular mechanisms of actin fusion focus formation
3: To identify the fusogen(s) promoting membrane fusion
4: To probe the GPCR signal for fusion initiation
5: To define the mechanism of fusion termination
By combining genetic, optogenetic, biochemical, live-imaging, synthetic and modeling approaches, this project will bring a molecular and conceptual understanding of cell fusion. This work will have far-ranging relevance for cell polarization, cytoskeletal organization, cell signalling and communication, and cell fate regulation.
Max ERC Funding
1 999 956 €
Duration
Start date: 2016-10-01, End date: 2021-09-30
Project acronym DIA
Project Deep Integration Agreements
Researcher (PI) Ralph Ossa
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Consolidator Grant (CoG), SH1, ERC-2018-COG
Summary This project aims to improve our understanding of deep integration agreements, which have generated an extraordinary amount of controversy in recent years. Unlike ordinary trade agreements, deep integration agreements do not just focus on reducing tariff barriers but seek to achieve much broader economic integration. Prominent examples include the Transatlantic Trade and Investment Partnership (TTIP) negotiated between the EU and the US and the Comprehensive Economic and Trade Agreement (CETA) negotiated between the EU and Canada.
I proceed in three complementary parts, focusing on the most controversial deep integration issues. In a first part, I consider provisions regarding investor protection including the Investor-State Dispute Settlement System. My ambition is to provide a comprehensive theoretical treatment of international investment agreements, which sheds light on their fundamental purpose and assesses their real-world design. In a second part, I turn to efforts towards regulatory cooperation such as CETA’s Regulatory Cooperation Forum. Here, my goal is again to provide a broad theoretical analysis, which identifies the scope for regulatory cooperation and makes suggestions for their real-world design. In a third part, I study intellectual property rights protection, specifically the agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). In particular, I propose to take a canonical model of intellectual property rights agreements to the data and quantitatively assess the efficiency and equity implications of TRIPS.
Summary
This project aims to improve our understanding of deep integration agreements, which have generated an extraordinary amount of controversy in recent years. Unlike ordinary trade agreements, deep integration agreements do not just focus on reducing tariff barriers but seek to achieve much broader economic integration. Prominent examples include the Transatlantic Trade and Investment Partnership (TTIP) negotiated between the EU and the US and the Comprehensive Economic and Trade Agreement (CETA) negotiated between the EU and Canada.
I proceed in three complementary parts, focusing on the most controversial deep integration issues. In a first part, I consider provisions regarding investor protection including the Investor-State Dispute Settlement System. My ambition is to provide a comprehensive theoretical treatment of international investment agreements, which sheds light on their fundamental purpose and assesses their real-world design. In a second part, I turn to efforts towards regulatory cooperation such as CETA’s Regulatory Cooperation Forum. Here, my goal is again to provide a broad theoretical analysis, which identifies the scope for regulatory cooperation and makes suggestions for their real-world design. In a third part, I study intellectual property rights protection, specifically the agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). In particular, I propose to take a canonical model of intellectual property rights agreements to the data and quantitatively assess the efficiency and equity implications of TRIPS.
Max ERC Funding
1 433 281 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym ENDOFUN
Project The endodermis - unraveling the function of an ancient barrier
Researcher (PI) Niko Geldner
Host Institution (HI) UNIVERSITE DE LAUSANNE
Call Details Consolidator Grant (CoG), LS3, ERC-2013-CoG
Summary In addition to maintaining homeostasis within their cells, multicellular organisms also need to control their inner, extracellular spaces between cells. In order to do so, epithelia have developed, bearing ring-like paracellular barriers, with specialised membrane surfaces facing either the environment or the inner space of the organism. In animals, such polarised epithelia use specialised protein assemblies, called tight junctions, to seal the extracellular space, which have been a topic of active research for decades. Plant roots need to extract inorganic elements from the soil. A plethora of transporters are expressed in plant roots, yet, as in animals, transporter action is contingent upon the presence of efficient paracellular (apoplastic) barriers. Therefore, an understanding of the development, structure and function of the root apoplastic barrier is crucial for mechanistic models of root nutrient uptake. The endodermis is the main apoplastic barrier in roots, but, in contrast to animals, molecular data about endodermal differentiation and function has been virtually absent. We recently gained insights into the factors that drive endodermal differentiation, largely due to efforts from my research team. Our work has led a foundation of mutants, markers and protocols that provide an unprecented opportunity to test the many supposed roles of the root endodermis. Our preliminary insights indicate that generally accepted views of endodermal function have been overly simplistic. The topic of this proposal is to develop better tools and much more precise molecular analysis of nutrient uptake, centered around the endodermis. I propose to investigate our specific barrier mutants with new tools that allow visualisation of changes in nutrient transport at cellular resolution. The results from this project will provide a new foundation for models of plant nutrition and help us to understand how plants manage, and sometimes fail, to extract what they need from the soil.
Summary
In addition to maintaining homeostasis within their cells, multicellular organisms also need to control their inner, extracellular spaces between cells. In order to do so, epithelia have developed, bearing ring-like paracellular barriers, with specialised membrane surfaces facing either the environment or the inner space of the organism. In animals, such polarised epithelia use specialised protein assemblies, called tight junctions, to seal the extracellular space, which have been a topic of active research for decades. Plant roots need to extract inorganic elements from the soil. A plethora of transporters are expressed in plant roots, yet, as in animals, transporter action is contingent upon the presence of efficient paracellular (apoplastic) barriers. Therefore, an understanding of the development, structure and function of the root apoplastic barrier is crucial for mechanistic models of root nutrient uptake. The endodermis is the main apoplastic barrier in roots, but, in contrast to animals, molecular data about endodermal differentiation and function has been virtually absent. We recently gained insights into the factors that drive endodermal differentiation, largely due to efforts from my research team. Our work has led a foundation of mutants, markers and protocols that provide an unprecented opportunity to test the many supposed roles of the root endodermis. Our preliminary insights indicate that generally accepted views of endodermal function have been overly simplistic. The topic of this proposal is to develop better tools and much more precise molecular analysis of nutrient uptake, centered around the endodermis. I propose to investigate our specific barrier mutants with new tools that allow visualisation of changes in nutrient transport at cellular resolution. The results from this project will provide a new foundation for models of plant nutrition and help us to understand how plants manage, and sometimes fail, to extract what they need from the soil.
Max ERC Funding
1 985 443 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym EXOKLEIN
Project The Climates and Habitability of Small Exoplanets Around Red Stars
Researcher (PI) Kevin HENG
Host Institution (HI) UNIVERSITAET BERN
Call Details Consolidator Grant (CoG), PE9, ERC-2017-COG
Summary The detection of life beyond our Solar System is possible only via the remote sensing of the atmospheres of exoplanets. The recent discovery that small exoplanets are common around cool, red stars offers an exciting opportunity to study the atmospheres of Earth-like worlds. Motivated by this revelation, the EXOKLEIN project proposes to construct a holistic climate framework to understand astronomical observations in the context of the atmosphere, geochemistry and biosignatures of the exoplanet. The proposed research is divided into three major themes. Research Theme 1 aims to construct a virtual laboratory of an atmosphere that considers atmospheric dynamics, chemistry and radiation, as well as how they interact. This virtual laboratory enables us to understand the physical and chemical mechanisms involved, as well as predict the observed properties of an exoplanet. Research Theme 2 aims to generalize the carbonate-silicate cycle (also known as the long-term carbon cycle) by considering variations in rock composition, water acidity and atmospheric conditions. The carbonate-silicate cycle is important because it regulates the long-term presence of carbon dioxide (a vital greenhouse gas) in atmospheres. We also aim to investigate the role of the cycle in determining the fates of ocean-dominated exoplanets called “water worlds”. Research Theme 3 aims to investigate the long-term stability of biosignature gases in the context of the climate. Whether a gas uniquely indicates the presence of biology on an exoplanet depends on the atmospheric properties and ultraviolet radiation environment. We investigate three prime candidates for biosignature gases: methyl chloride, dimethylsulfide and ammonia. Overall, the EXOKLEIN project will significantly advance our understanding of whether the environments of rocky exoplanets around red stars are stable and conducive for life, and whether the tell-tale signatures of life may be detected by astronomers.
Summary
The detection of life beyond our Solar System is possible only via the remote sensing of the atmospheres of exoplanets. The recent discovery that small exoplanets are common around cool, red stars offers an exciting opportunity to study the atmospheres of Earth-like worlds. Motivated by this revelation, the EXOKLEIN project proposes to construct a holistic climate framework to understand astronomical observations in the context of the atmosphere, geochemistry and biosignatures of the exoplanet. The proposed research is divided into three major themes. Research Theme 1 aims to construct a virtual laboratory of an atmosphere that considers atmospheric dynamics, chemistry and radiation, as well as how they interact. This virtual laboratory enables us to understand the physical and chemical mechanisms involved, as well as predict the observed properties of an exoplanet. Research Theme 2 aims to generalize the carbonate-silicate cycle (also known as the long-term carbon cycle) by considering variations in rock composition, water acidity and atmospheric conditions. The carbonate-silicate cycle is important because it regulates the long-term presence of carbon dioxide (a vital greenhouse gas) in atmospheres. We also aim to investigate the role of the cycle in determining the fates of ocean-dominated exoplanets called “water worlds”. Research Theme 3 aims to investigate the long-term stability of biosignature gases in the context of the climate. Whether a gas uniquely indicates the presence of biology on an exoplanet depends on the atmospheric properties and ultraviolet radiation environment. We investigate three prime candidates for biosignature gases: methyl chloride, dimethylsulfide and ammonia. Overall, the EXOKLEIN project will significantly advance our understanding of whether the environments of rocky exoplanets around red stars are stable and conducive for life, and whether the tell-tale signatures of life may be detected by astronomers.
Max ERC Funding
1 984 729 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym FOUR ACES
Project Future of upper atmospheric characterisation of exoplanets with spectroscopy
Researcher (PI) David René Bernard EHRENREICH
Host Institution (HI) UNIVERSITE DE GENEVE
Call Details Consolidator Grant (CoG), PE9, ERC-2016-COG
Summary This project will open a new path to characterise the atmospheres of exoplanets down to Earth-size objects, using the spatial extension of upper atmospheres as a magnifying glass to access the atmospheric properties. The tremendous energy received by exoplanets close to their stars leads to dramatic atmospheric expansion and escape, which could result in the formation of hot rocky super-Earths seen in recent years. While the escape mechanisms and evolutionary impact on planets and atmospheres remain debated, the atmospheric expansion gives rise to spectacular spectroscopic signatures in the UV, only detectable with the Hubble Space Telescope (HST). In 2015, I discovered a huge extended atmosphere escaping from a “warm Neptune”, which represents a milestone on the road to the atmospheres of lower-mass, more temperate planets. Using HARPS spectroscopy from the ground, I revealed the extreme conditions in the upper atmosphere of a “hot Jupiter”, probing the onset of atmospheric escape in the optical, linking the upper and lower atmospheres. I propose to consolidate these breakthroughs via a thorough exploitation of the vast amount of observations I obtained for ~20 planets (100+ hours on HST and 250+ hours on HARPS and HARPS-N) in the wake of my results. I will use those data to bind theories describing the lower and upper atmospheres of exoplanets, and determine how these are impacted by stellar activity. In a second step, I will build and deliver a legacy archive of UV observations by the end of HST in ~2020. In an era where new transit surveys will provide hundreds of easier-to-study exoplanets transiting bright stars, I will use my priviledged access to the reconnaissance capabilities of the ESA CHEOPS mission (2018–2022) to cherry-pick the very best planets for atmospheric characterisation. I will combine the space-borne and ground-based high-resolution spectroscopic follow-ups of these planets to deliver a novel, comprehensive view of exoplanetary atmospheres.
Summary
This project will open a new path to characterise the atmospheres of exoplanets down to Earth-size objects, using the spatial extension of upper atmospheres as a magnifying glass to access the atmospheric properties. The tremendous energy received by exoplanets close to their stars leads to dramatic atmospheric expansion and escape, which could result in the formation of hot rocky super-Earths seen in recent years. While the escape mechanisms and evolutionary impact on planets and atmospheres remain debated, the atmospheric expansion gives rise to spectacular spectroscopic signatures in the UV, only detectable with the Hubble Space Telescope (HST). In 2015, I discovered a huge extended atmosphere escaping from a “warm Neptune”, which represents a milestone on the road to the atmospheres of lower-mass, more temperate planets. Using HARPS spectroscopy from the ground, I revealed the extreme conditions in the upper atmosphere of a “hot Jupiter”, probing the onset of atmospheric escape in the optical, linking the upper and lower atmospheres. I propose to consolidate these breakthroughs via a thorough exploitation of the vast amount of observations I obtained for ~20 planets (100+ hours on HST and 250+ hours on HARPS and HARPS-N) in the wake of my results. I will use those data to bind theories describing the lower and upper atmospheres of exoplanets, and determine how these are impacted by stellar activity. In a second step, I will build and deliver a legacy archive of UV observations by the end of HST in ~2020. In an era where new transit surveys will provide hundreds of easier-to-study exoplanets transiting bright stars, I will use my priviledged access to the reconnaissance capabilities of the ESA CHEOPS mission (2018–2022) to cherry-pick the very best planets for atmospheric characterisation. I will combine the space-borne and ground-based high-resolution spectroscopic follow-ups of these planets to deliver a novel, comprehensive view of exoplanetary atmospheres.
Max ERC Funding
1 999 475 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym GREinGC
Project General Relativistic Effect in Galaxy Clustering as a Novel Probe of Inflationary Cosmology
Researcher (PI) Jaiyul Yoo
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Consolidator Grant (CoG), PE9, ERC-2015-CoG
Summary Substantial advances in cosmology over the past decades have firmly established the standard model of cosmology. However, the physical nature of the early Universe and dark energy (or inflationary cosmology) remains poorly understood. To resolve these issues, a large number of galaxy surveys are planned to measure millions of galaxies in the sky, promising precision measurements of galaxy clustering with enormous statistical power. Despite these advances in observation, the standard theoretical description of galaxy clustering is based on the Newtonian description, inadequate for measuring the relativistic effects from the early Universe and the deviations of modified gravity from general relativity. In recent years, the applicant, for the first time, developed the linear-order general relativistic description of galaxy clustering and showed that the relativistic effect in galaxy clustering is already measurable at a few-sigma level in current surveys like the Sloan survey
and significant detections (>10 sigma) are possible in upcoming surveys.
This research proposal will aim to use the subtle relativistic effect in galaxy clustering to develop novel probes of inflationary cosmology. In particular, the applicant will 1) formulate the higher-order relativistic description of galaxy clustering, an essential tool for computing the bispectrum, and 2) investigate the unique relativistic signatures (linear-order and higher-order) in galaxy clustering from the early Universe and dark energy to develop novel probes of isolating those signatures and to quantify their detectabilities in future galaxy surveys. Biases in cosmological parameter estimation, if the standard Newtonian description is used, will be quantified. A comprehensive understanding of inflationary cosmology will have far-reaching consequences, shedding light on new physics beyond the standard model.
Summary
Substantial advances in cosmology over the past decades have firmly established the standard model of cosmology. However, the physical nature of the early Universe and dark energy (or inflationary cosmology) remains poorly understood. To resolve these issues, a large number of galaxy surveys are planned to measure millions of galaxies in the sky, promising precision measurements of galaxy clustering with enormous statistical power. Despite these advances in observation, the standard theoretical description of galaxy clustering is based on the Newtonian description, inadequate for measuring the relativistic effects from the early Universe and the deviations of modified gravity from general relativity. In recent years, the applicant, for the first time, developed the linear-order general relativistic description of galaxy clustering and showed that the relativistic effect in galaxy clustering is already measurable at a few-sigma level in current surveys like the Sloan survey
and significant detections (>10 sigma) are possible in upcoming surveys.
This research proposal will aim to use the subtle relativistic effect in galaxy clustering to develop novel probes of inflationary cosmology. In particular, the applicant will 1) formulate the higher-order relativistic description of galaxy clustering, an essential tool for computing the bispectrum, and 2) investigate the unique relativistic signatures (linear-order and higher-order) in galaxy clustering from the early Universe and dark energy to develop novel probes of isolating those signatures and to quantify their detectabilities in future galaxy surveys. Biases in cosmological parameter estimation, if the standard Newtonian description is used, will be quantified. A comprehensive understanding of inflationary cosmology will have far-reaching consequences, shedding light on new physics beyond the standard model.
Max ERC Funding
1 991 721 €
Duration
Start date: 2016-03-01, End date: 2021-02-28
Project acronym STEMBAR
Project Mechanisms and functional significance of diffusion barriers for asymmetric segregation of age in neural stem cells
Researcher (PI) Sebastian Jessberger
Host Institution (HI) UNIVERSITAT ZURICH
Call Details Consolidator Grant (CoG), LS3, ERC-2015-CoG
Summary Neural stem/progenitor cells (NSPCs) continue to generate new neurons throughout life in distinct regions of the mammalian brain. Adult neurogenesis has been implicated in brain function and altered neurogenesis has been associated with a number of neuropsychiatric diseases such as depression and cognitive ageing. A key feature of somatic stem cell division is the ability to divide asymmetrically and symmetrically for neurogenic and self-renewing cell division, respectively. However, it remains unknown how age is segregated in the context of somatic stem cell division, i.e., if the cellular history and the replicative age of the mother stem cell is passed onto its progeny. Thus, we hypothesized that – similar to the previously described barrier that exists in budding yeast – somatic stem cells, and more specifically NSPCs, form a diffusion barrier during cell division to retain aging or senescence factors within the stem cell, generating a mechanism for how age is asymmetrically distributed. Indeed, we found the existence of a diffusion barrier that is established during NSPC division, identifying a new mechanism of cellular segregation and asymmetry. With the program proposed here I aim i) to study the effects of the barrier on asymmetric segregation of aging factors and to develop novel tools to visualize the mammalian diffusion barrier, ii) to characterize the presence of a diffusion barrier in endogenous NSPCs in relation to cell division history, iii) to analyse the mechanisms underlying age-associated weakening of the NSPC diffusion barrier, and iv) to evaluate if genetic and pharmacological rescue of the barrier is sufficient to ameliorate the age-dependent decline of neurogenesis. The insights gained from the studies proposed here have the potential to substantially advance our understanding of NSPC biology, to identify a new mechanism underlying the neurogenic process, and to reshape our understanding of asymmetric cell division of somatic stem cells.
Summary
Neural stem/progenitor cells (NSPCs) continue to generate new neurons throughout life in distinct regions of the mammalian brain. Adult neurogenesis has been implicated in brain function and altered neurogenesis has been associated with a number of neuropsychiatric diseases such as depression and cognitive ageing. A key feature of somatic stem cell division is the ability to divide asymmetrically and symmetrically for neurogenic and self-renewing cell division, respectively. However, it remains unknown how age is segregated in the context of somatic stem cell division, i.e., if the cellular history and the replicative age of the mother stem cell is passed onto its progeny. Thus, we hypothesized that – similar to the previously described barrier that exists in budding yeast – somatic stem cells, and more specifically NSPCs, form a diffusion barrier during cell division to retain aging or senescence factors within the stem cell, generating a mechanism for how age is asymmetrically distributed. Indeed, we found the existence of a diffusion barrier that is established during NSPC division, identifying a new mechanism of cellular segregation and asymmetry. With the program proposed here I aim i) to study the effects of the barrier on asymmetric segregation of aging factors and to develop novel tools to visualize the mammalian diffusion barrier, ii) to characterize the presence of a diffusion barrier in endogenous NSPCs in relation to cell division history, iii) to analyse the mechanisms underlying age-associated weakening of the NSPC diffusion barrier, and iv) to evaluate if genetic and pharmacological rescue of the barrier is sufficient to ameliorate the age-dependent decline of neurogenesis. The insights gained from the studies proposed here have the potential to substantially advance our understanding of NSPC biology, to identify a new mechanism underlying the neurogenic process, and to reshape our understanding of asymmetric cell division of somatic stem cells.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
