Project acronym A-FRO
Project Actively Frozen - contextual modulation of freezing and its neuronal basis
Researcher (PI) Marta de Aragao Pacheco Moita
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Country Portugal
Call Details Consolidator Grant (CoG), LS5, ERC-2018-COG
Summary When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.
Summary
When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.
Max ERC Funding
1 969 750 €
Duration
Start date: 2019-02-01, End date: 2024-01-31
Project acronym AGILEFLIGHT
Project Low-latency Perception and Action for Agile Vision-based Flight
Researcher (PI) Davide SCARAMUZZA
Host Institution (HI) UNIVERSITAT ZURICH
Country Switzerland
Call Details Consolidator Grant (CoG), PE7, ERC-2019-COG
Summary Drones are disrupting industries, such as agriculture, package delivery, inspection, and search and rescue. However, they are still either controlled by a human pilot or heavily rely on GPS for navigating autonomously. The alternative to GPS are onboard sensors, such as cameras: from the raw data, a local 3D map of the environment is built, which is then used to plan a safe trajectory to the goal. While the underlying algorithms are well understood, we are still far from having autonomous drones that can navigate through complex environments as good as human pilots. State-of-the-art perception and control algorithms are mature but not robust: coping with unreliable state estimation, low-latency perception, real-time planning in dynamic environments, and tight coupling of perception and action under severe resource constraints are all still unsolved research problems. Another issue is that, because battery energy density is increasing at a very slow rate, drones need to navigate faster in order to accomplish more within their limited flight time. To obtain more agile robots, we need faster sensors and low-latency processing.
The goal of this project is to develop novel scientific methods that would allow me to demonstrate autonomous, vision-based, agile quadrotor navigation in unknown, GPS-denied, and cluttered environments with possibly moving obstacles, which can be as effective in terms of maneuverability and agility as those of professional drone pilots. The outcome would not only be beneficial for disaster response scenarios, but also for other scenarios, such as aerial delivery or inspection. To achieve this ambitious goal, I will first develop robust, low-latency, multimodal perception algorithms that combine the advantages of standard cameras with event cameras. Then, I will develop novel methods that unify perception and state estimation together with planning and control to enable agile maneuvers through cluttered, unknown, and dynamic environments.
Summary
Drones are disrupting industries, such as agriculture, package delivery, inspection, and search and rescue. However, they are still either controlled by a human pilot or heavily rely on GPS for navigating autonomously. The alternative to GPS are onboard sensors, such as cameras: from the raw data, a local 3D map of the environment is built, which is then used to plan a safe trajectory to the goal. While the underlying algorithms are well understood, we are still far from having autonomous drones that can navigate through complex environments as good as human pilots. State-of-the-art perception and control algorithms are mature but not robust: coping with unreliable state estimation, low-latency perception, real-time planning in dynamic environments, and tight coupling of perception and action under severe resource constraints are all still unsolved research problems. Another issue is that, because battery energy density is increasing at a very slow rate, drones need to navigate faster in order to accomplish more within their limited flight time. To obtain more agile robots, we need faster sensors and low-latency processing.
The goal of this project is to develop novel scientific methods that would allow me to demonstrate autonomous, vision-based, agile quadrotor navigation in unknown, GPS-denied, and cluttered environments with possibly moving obstacles, which can be as effective in terms of maneuverability and agility as those of professional drone pilots. The outcome would not only be beneficial for disaster response scenarios, but also for other scenarios, such as aerial delivery or inspection. To achieve this ambitious goal, I will first develop robust, low-latency, multimodal perception algorithms that combine the advantages of standard cameras with event cameras. Then, I will develop novel methods that unify perception and state estimation together with planning and control to enable agile maneuvers through cluttered, unknown, and dynamic environments.
Max ERC Funding
2 000 000 €
Duration
Start date: 2020-09-01, End date: 2025-08-31
Project acronym AimingT6SS
Project Mechanisms of dynamic localization of the bacterial Type 6 secretion system assembly
Researcher (PI) Marek BASLER
Host Institution (HI) UNIVERSITAT BASEL
Country Switzerland
Call Details Consolidator Grant (CoG), LS6, ERC-2019-COG
Summary The Type 6 secretion system (T6SS) allows Gram-negative bacteria to deliver toxins into both eukaryotic and bacterial target cells and thus cause disease or kill competitors. T6SS is composed of four main parts: a membrane complex, a baseplate and a long spring-like sheath wrapped around an inner tube. Sheath contraction generates a large amount of energy to push the tube with associated toxins through the baseplate and membrane complex out of the cell. However, the reach of the T6SS tube is limited and thus a direct contact with the target membrane and precise positioning of T6SS assembly is required for protein translocation. In this proposal, we will unravel principles of spatial and temporal coordination of T6SS assembly that we have recently observed in several bacterial species. We will study how cells sense attacks from neighboring bacteria to dynamically localize its T6SS. We will describe how bacteria initiate and position T6SS assembly in response to physical cell-cell interactions. We will identify the principles and the role of T6SS localization in intracellular pathogens. Using genetic and biochemical approaches, we will identify and characterize proteins interacting with the core components of T6SS and test their role in initiation and positioning of T6SS assembly. We will search for peptidoglycan remodeling enzymes required for T6SS assembly. We will use advanced microscopy techniques to describe dynamic localization of proteins upon T6SS activation to establish the order of their assembly. We will quantify how much T6SS aiming increases efficiency of protein delivery and T6SS function during bacterial competition and pathogenesis. Overall, we will unravel novel principles of spatial and temporal control of localization of protein complexes and show how this allows bacteria to quickly respond to external cues and interact with their environment.
Summary
The Type 6 secretion system (T6SS) allows Gram-negative bacteria to deliver toxins into both eukaryotic and bacterial target cells and thus cause disease or kill competitors. T6SS is composed of four main parts: a membrane complex, a baseplate and a long spring-like sheath wrapped around an inner tube. Sheath contraction generates a large amount of energy to push the tube with associated toxins through the baseplate and membrane complex out of the cell. However, the reach of the T6SS tube is limited and thus a direct contact with the target membrane and precise positioning of T6SS assembly is required for protein translocation. In this proposal, we will unravel principles of spatial and temporal coordination of T6SS assembly that we have recently observed in several bacterial species. We will study how cells sense attacks from neighboring bacteria to dynamically localize its T6SS. We will describe how bacteria initiate and position T6SS assembly in response to physical cell-cell interactions. We will identify the principles and the role of T6SS localization in intracellular pathogens. Using genetic and biochemical approaches, we will identify and characterize proteins interacting with the core components of T6SS and test their role in initiation and positioning of T6SS assembly. We will search for peptidoglycan remodeling enzymes required for T6SS assembly. We will use advanced microscopy techniques to describe dynamic localization of proteins upon T6SS activation to establish the order of their assembly. We will quantify how much T6SS aiming increases efficiency of protein delivery and T6SS function during bacterial competition and pathogenesis. Overall, we will unravel novel principles of spatial and temporal control of localization of protein complexes and show how this allows bacteria to quickly respond to external cues and interact with their environment.
Max ERC Funding
2 493 650 €
Duration
Start date: 2021-01-01, End date: 2025-12-31
Project acronym AMADEUS
Project Advancing CO2 Capture Materials by Atomic Scale Design: the Quest for Understanding
Researcher (PI) Christoph Ruediger MueLLER
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Consolidator Grant (CoG), PE8, ERC-2018-COG
Summary Carbon dioxide capture and storage is a technology to mitigate climate change by removing CO2 from flue gas streams or the atmosphere and storing it in geological formations. While CO2 removal from natural gas by amine scrubbing is implemented on the large scale, the cost of such process is currently prohibitively expensive. Inexpensive alkali earth metal oxides (MgO and CaO) feature high theoretical CO2 uptakes, but suffer from poor cyclic stability and slow kinetics. Yet, the key objective of recent research on alkali earth metal oxide based CO2 sorbents has been the processing of inexpensive, naturally occurring CO2 sorbents, notably limestone and dolomite, to stabilize their modest CO2 uptake and to establish re-activation methods through engineering approaches. While this research demonstrated a landmark Megawatt (MW) scale viability of the process, our fundamental understanding of the underlying CO2 capture, regeneration and deactivation pathways did not improve. The latter knowledge is, however, vital for the rational design of improved, yet practical CaO and MgO sorbents. Hence this proposal is concerned with obtaining an understanding of the underlying mechanisms that control the ability of an alkali metal oxide to capture a large quantity of CO2 with a high rate, to regenerate and to operate with high cyclic stability. Achieving these aims relies on the ability to fabricate model structures and to characterize in great detail their surface chemistry, morphology, chemical composition and changes therein under reactive conditions. This makes the development of operando and in situ characterization tools an essential prerequisite. Advances in these areas shall allow achieving the overall goal of this project, viz. to formulate a roadmap to fabricate improved CO2 sorbents through their precisely engineered structure, composition and morphology.
Summary
Carbon dioxide capture and storage is a technology to mitigate climate change by removing CO2 from flue gas streams or the atmosphere and storing it in geological formations. While CO2 removal from natural gas by amine scrubbing is implemented on the large scale, the cost of such process is currently prohibitively expensive. Inexpensive alkali earth metal oxides (MgO and CaO) feature high theoretical CO2 uptakes, but suffer from poor cyclic stability and slow kinetics. Yet, the key objective of recent research on alkali earth metal oxide based CO2 sorbents has been the processing of inexpensive, naturally occurring CO2 sorbents, notably limestone and dolomite, to stabilize their modest CO2 uptake and to establish re-activation methods through engineering approaches. While this research demonstrated a landmark Megawatt (MW) scale viability of the process, our fundamental understanding of the underlying CO2 capture, regeneration and deactivation pathways did not improve. The latter knowledge is, however, vital for the rational design of improved, yet practical CaO and MgO sorbents. Hence this proposal is concerned with obtaining an understanding of the underlying mechanisms that control the ability of an alkali metal oxide to capture a large quantity of CO2 with a high rate, to regenerate and to operate with high cyclic stability. Achieving these aims relies on the ability to fabricate model structures and to characterize in great detail their surface chemistry, morphology, chemical composition and changes therein under reactive conditions. This makes the development of operando and in situ characterization tools an essential prerequisite. Advances in these areas shall allow achieving the overall goal of this project, viz. to formulate a roadmap to fabricate improved CO2 sorbents through their precisely engineered structure, composition and morphology.
Max ERC Funding
1 994 900 €
Duration
Start date: 2019-06-01, End date: 2024-05-31
Project acronym BactInd
Project Bacterial cooperation at the individual cell level
Researcher (PI) Rolf Kuemmerli
Host Institution (HI) UNIVERSITAT ZURICH
Country Switzerland
Call Details Consolidator Grant (CoG), LS8, ERC-2015-CoG
Summary All levels of life entail cooperation and conflict. Genes cooperate to build up a functional genome, which can yet be undermined by selfish genetic elements. Humans and animals cooperate to build up societies, which can yet be subverted by cheats. There is a long-standing interest among biologists to comprehend the tug-of-war between cooperation and conflict. Recently, research on bacteria was successful in identifying key factors that can tip the balance in favour or against cooperation. Bacteria cooperate through the formation of protective biofilms, cell-to-cell communication, and the secretion of shareable public goods. However, the advantage of bacteria being fast replicating units, easily cultivatable in high numbers, is also their disadvantage: they are small and imperceptible, such that measures of cooperation typically rely on averaged responses across millions of cells. Thus, we still know very little about bacterial cooperation at the biological relevant scale: the individual cell level. Here, I present research using the secretion of public goods in the opportunistic human pathogen Pseudomonas aeruginosa, to tackle this issue. I will explore new dimensions of bacterial cooperation by asking whether bacteria engage in collective-decision making to find optimal group-level solutions; whether bacteria show division of labour to split up work efficiently; and whether bacteria can distinguish between trustworthy and cheating partners. The proposed research will make two significant contributions. First, it will reveal whether bacteria engage in complex forms of cooperation (collective decision-making, division of labour, partner recognition), which have traditionally been associated with higher organisms. Second, it will provide insights into the evolutionary stability of cooperation – key knowledge for designing therapies that interfere with virulence-inducing public goods in infections, and the design of stable public-good based remediation processes.
Summary
All levels of life entail cooperation and conflict. Genes cooperate to build up a functional genome, which can yet be undermined by selfish genetic elements. Humans and animals cooperate to build up societies, which can yet be subverted by cheats. There is a long-standing interest among biologists to comprehend the tug-of-war between cooperation and conflict. Recently, research on bacteria was successful in identifying key factors that can tip the balance in favour or against cooperation. Bacteria cooperate through the formation of protective biofilms, cell-to-cell communication, and the secretion of shareable public goods. However, the advantage of bacteria being fast replicating units, easily cultivatable in high numbers, is also their disadvantage: they are small and imperceptible, such that measures of cooperation typically rely on averaged responses across millions of cells. Thus, we still know very little about bacterial cooperation at the biological relevant scale: the individual cell level. Here, I present research using the secretion of public goods in the opportunistic human pathogen Pseudomonas aeruginosa, to tackle this issue. I will explore new dimensions of bacterial cooperation by asking whether bacteria engage in collective-decision making to find optimal group-level solutions; whether bacteria show division of labour to split up work efficiently; and whether bacteria can distinguish between trustworthy and cheating partners. The proposed research will make two significant contributions. First, it will reveal whether bacteria engage in complex forms of cooperation (collective decision-making, division of labour, partner recognition), which have traditionally been associated with higher organisms. Second, it will provide insights into the evolutionary stability of cooperation – key knowledge for designing therapies that interfere with virulence-inducing public goods in infections, and the design of stable public-good based remediation processes.
Max ERC Funding
1 994 981 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym BUNGEE
Project Directed crop breeding using jumping genes
Researcher (PI) Etienne BUCHER
Host Institution (HI) EIDGENOESSISCHES DEPARTEMENT FUER WIRTSCHAFT, BILDUNG UND FORSCHUNG
Country Switzerland
Call Details Consolidator Grant (CoG), LS9, ERC-2016-COG
Summary The rapidly changing climate puts commonly used crop plants under strong pressure. It is therefore essential to develop novel breeding technologies to rapidly enhance crops to better withstand newly emerging stresses.
Interestingly, a clear link between transposable elements (TEs), crop improvement and varietal diversification exists. Furthermore, in recent years the importance of (TEs) in evolution and adaptation to stresses has been recognized. However the use of TEs in crop breeding is currently very limited because it is not possible to control TE mobility. My research group has identified a novel highly conserved epigenetic silencing mechanism that represses the activity of TEs in Arabidopsis. We also found drugs capable of inhibiting this mechanism. Because these drugs target highly conserved enzymes we were able to show that our drug treatment is also effective in rice. We are therefore able to produce TE bursts in a controlled manner in virtually any plant. We can thus, for the first time, generate and study TE bursts in crop plants in real time. More importantly, we found that the accumulation of novel insertions of a heat-stress inducible TE produced plants that, at a high frequency, were more resistant to heat stress. This suggests that the stress that was initially applied to activate a specific TE in the parent, lead to an improved tolerance to that specific stress in the progeny of that plant in a very straight-forward manner.
In this project I propose to accelerate plant breeding by testing and implementing a revolutionary TE-directed crop improvement technology. For that I plan to 1. Mobilize TEs in crop plants using selected stresses 2. Using these mobilized stress-responsive TEs breed novel crop plants resistant to those selected stresses and 3. Study the genetic and epigenetic impact of TE mobilization on host genomes. This project will have a broad impact on crop improvement and on the basic understanding of the evolutionary importance of TEs.
Summary
The rapidly changing climate puts commonly used crop plants under strong pressure. It is therefore essential to develop novel breeding technologies to rapidly enhance crops to better withstand newly emerging stresses.
Interestingly, a clear link between transposable elements (TEs), crop improvement and varietal diversification exists. Furthermore, in recent years the importance of (TEs) in evolution and adaptation to stresses has been recognized. However the use of TEs in crop breeding is currently very limited because it is not possible to control TE mobility. My research group has identified a novel highly conserved epigenetic silencing mechanism that represses the activity of TEs in Arabidopsis. We also found drugs capable of inhibiting this mechanism. Because these drugs target highly conserved enzymes we were able to show that our drug treatment is also effective in rice. We are therefore able to produce TE bursts in a controlled manner in virtually any plant. We can thus, for the first time, generate and study TE bursts in crop plants in real time. More importantly, we found that the accumulation of novel insertions of a heat-stress inducible TE produced plants that, at a high frequency, were more resistant to heat stress. This suggests that the stress that was initially applied to activate a specific TE in the parent, lead to an improved tolerance to that specific stress in the progeny of that plant in a very straight-forward manner.
In this project I propose to accelerate plant breeding by testing and implementing a revolutionary TE-directed crop improvement technology. For that I plan to 1. Mobilize TEs in crop plants using selected stresses 2. Using these mobilized stress-responsive TEs breed novel crop plants resistant to those selected stresses and 3. Study the genetic and epigenetic impact of TE mobilization on host genomes. This project will have a broad impact on crop improvement and on the basic understanding of the evolutionary importance of TEs.
Max ERC Funding
1 965 625 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym CapTherPV
Project Integration of Capacitor, Thermoelectric and PhotoVoltaic thin films for efficient energy conversion and storage
Researcher (PI) Isabel Maria Das Merces Ferreira
Host Institution (HI) NOVA ID FCT - ASSOCIACAO PARA A INOVACAO E DESENVOLVIMENTO DA FCT
Country Portugal
Call Details Consolidator Grant (CoG), PE8, ERC-2014-CoG
Summary The possibility of having a unique device that converts thermal and photonics energy into electrical energy and simultaneously stores it, is something dreamed by the PI since the beginning of her research career. To achieve that goal, this project aims to gather, in a single substrate, solar cells with up-conversion nanoparticles, thermoelectrics and graphene super-capacitor, all made of thin films. These three main components will be developed separately and integrated sequentially. The innovation proposed is not limited to the integration of components, but rely in ground-breaking concepts: 1) thermoelectric elements based on thin film (TE-TF) oxides; 2) plasmonic nanoparticles for up conversion of near infrared radiation to visible emission in solar cells; 3) graphene super-capacitors; 4) integration and optimization of all components in a single CapTherPV device. This ambitious project will bring new insights at large area, low cost and flexible energy harvesting and comes from an old idea of combining energy conversion and storage that has been pursued by the PI. She started her career in amorphous silicon thin film solar cells, later she started the development of thin film batteries and more recently started a research line in thermoelectric films. If approved, this project will give financial support to consolidate the research being carried out and will give independence to the PI in terms of resources and creative think. More importantly, will facilitate the concretization of the dream that has been pursued with hard work.
Summary
The possibility of having a unique device that converts thermal and photonics energy into electrical energy and simultaneously stores it, is something dreamed by the PI since the beginning of her research career. To achieve that goal, this project aims to gather, in a single substrate, solar cells with up-conversion nanoparticles, thermoelectrics and graphene super-capacitor, all made of thin films. These three main components will be developed separately and integrated sequentially. The innovation proposed is not limited to the integration of components, but rely in ground-breaking concepts: 1) thermoelectric elements based on thin film (TE-TF) oxides; 2) plasmonic nanoparticles for up conversion of near infrared radiation to visible emission in solar cells; 3) graphene super-capacitors; 4) integration and optimization of all components in a single CapTherPV device. This ambitious project will bring new insights at large area, low cost and flexible energy harvesting and comes from an old idea of combining energy conversion and storage that has been pursued by the PI. She started her career in amorphous silicon thin film solar cells, later she started the development of thin film batteries and more recently started a research line in thermoelectric films. If approved, this project will give financial support to consolidate the research being carried out and will give independence to the PI in terms of resources and creative think. More importantly, will facilitate the concretization of the dream that has been pursued with hard work.
Max ERC Funding
1 999 375 €
Duration
Start date: 2015-07-01, End date: 2021-09-30
Project acronym CELLFITNESS
Project Active Mechanisms of Cell Selection: From Cell Competition to Cell Fitness
Researcher (PI) Eduardo Moreno Lampaya
Host Institution (HI) FUNDACAO D. ANNA SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Country Portugal
Call Details Consolidator Grant (CoG), LS3, ERC-2013-CoG
Summary The molecular mechanisms that mediate cell competition, cell fitness and cell selection is gaining interest. With innovative approaches, molecules and ground-breaking hypothesis, this field of research can help understand several biological processes such as development, cancer and tissue degeneration. The project has 3 clear and ambitious objectives: 1. We propose to identify all the key genes mediating cell competition and their molecular mechanisms. In order to reach this objective we will use data from two whole genome screens in Drosophila where we have identified 7 key genes. By the end of this CoG grant, we should have no big gaps in our knowledge of how slow dividing cells are recognised and eliminated in Drosophila. 2. In addition, we will explore how general the cell competition pathways are and how they can impact biomedical research, with a focus in cancer and tissue degeneration. The interest in cancer is based on experiments in Drosophila and mice where we and others have found that an active process of cell selection determines tumour growth. Preliminary results suggest that the pathways identified do not only play important roles in the elimination of slow dividing cells, but also during cancer initiation and progression. 3. We will further explore the role of cell competition in neuronal selection, specially during neurodegeneration, development of the retina and adult brain regeneration in Drosophila. This proposal is of an interdisciplinary nature because it takes a basic cellular mechanism (the genetic pathways that select cells within tissues) and crosses boundaries between different fields of research: development, cancer, regeneration and tissue degeneration. In this ERC CoG proposal, we are committed to continue our efforts from basic science to biomedical approaches. The phenomena of cell competition and its participating genes have the potential to discover novel biomarkers and therapeutic strategies against cancer and tissue degeneration.
Summary
The molecular mechanisms that mediate cell competition, cell fitness and cell selection is gaining interest. With innovative approaches, molecules and ground-breaking hypothesis, this field of research can help understand several biological processes such as development, cancer and tissue degeneration. The project has 3 clear and ambitious objectives: 1. We propose to identify all the key genes mediating cell competition and their molecular mechanisms. In order to reach this objective we will use data from two whole genome screens in Drosophila where we have identified 7 key genes. By the end of this CoG grant, we should have no big gaps in our knowledge of how slow dividing cells are recognised and eliminated in Drosophila. 2. In addition, we will explore how general the cell competition pathways are and how they can impact biomedical research, with a focus in cancer and tissue degeneration. The interest in cancer is based on experiments in Drosophila and mice where we and others have found that an active process of cell selection determines tumour growth. Preliminary results suggest that the pathways identified do not only play important roles in the elimination of slow dividing cells, but also during cancer initiation and progression. 3. We will further explore the role of cell competition in neuronal selection, specially during neurodegeneration, development of the retina and adult brain regeneration in Drosophila. This proposal is of an interdisciplinary nature because it takes a basic cellular mechanism (the genetic pathways that select cells within tissues) and crosses boundaries between different fields of research: development, cancer, regeneration and tissue degeneration. In this ERC CoG proposal, we are committed to continue our efforts from basic science to biomedical approaches. The phenomena of cell competition and its participating genes have the potential to discover novel biomarkers and therapeutic strategies against cancer and tissue degeneration.
Max ERC Funding
1 968 062 €
Duration
Start date: 2014-06-01, End date: 2019-05-31
Project acronym CELLFUSION
Project Molecular dissection of the mechanisms of cell-cell fusion in the fission yeast
Researcher (PI) Sophie Genevieve Elisabeth Martin Benton
Host Institution (HI) UNIVERSITE DE LAUSANNE
Country Switzerland
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 CELPRED
Project Circuit elements of the cortical circuit for predictive processing
Researcher (PI) Georg KELLER
Host Institution (HI) FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Country Switzerland
Call Details Consolidator Grant (CoG), LS5, ERC-2019-COG
Summary One promising theoretical framework to explain the function of cortex is predictive processing. It postulates that cortex functions by maintaining an internal model, or internal representation, of the world through a comparison of predictions based on this internal model with incoming sensory information. Implementing predictive processing in a cortical circuit would require a set of distinct functional cell types. These would include neurons that compute a difference between top-down predictions and bottom-up input, referred to as prediction error neurons, and a separate population of neurons that integrate the output of prediction error neurons to maintain an internal representation of the world. This research proposal will test the framework of predictive processing and identify different putative circuit elements and cell types that are thought to form the circuit in mouse visual cortex. We will use a combination of physiological recordings, optogenetic manipulations of neural activity, and gene expression measurements to determine the cell types that have functional responses consistent with different prediction errors, as well as those coding for the internal representation. Identifying the circuit elements underlying predictive processing in cortex may reveal a strategy to bias processing either towards top-down or bottom-up drive when the balance between the two is perturbed, as may be the case in neuropsychiatric disorders.
Summary
One promising theoretical framework to explain the function of cortex is predictive processing. It postulates that cortex functions by maintaining an internal model, or internal representation, of the world through a comparison of predictions based on this internal model with incoming sensory information. Implementing predictive processing in a cortical circuit would require a set of distinct functional cell types. These would include neurons that compute a difference between top-down predictions and bottom-up input, referred to as prediction error neurons, and a separate population of neurons that integrate the output of prediction error neurons to maintain an internal representation of the world. This research proposal will test the framework of predictive processing and identify different putative circuit elements and cell types that are thought to form the circuit in mouse visual cortex. We will use a combination of physiological recordings, optogenetic manipulations of neural activity, and gene expression measurements to determine the cell types that have functional responses consistent with different prediction errors, as well as those coding for the internal representation. Identifying the circuit elements underlying predictive processing in cortex may reveal a strategy to bias processing either towards top-down or bottom-up drive when the balance between the two is perturbed, as may be the case in neuropsychiatric disorders.
Max ERC Funding
2 000 000 €
Duration
Start date: 2020-02-01, End date: 2025-01-31
