Project acronym AGRISCENTS
Project Scents and sensibility in agriculture: exploiting specificity in herbivore- and pathogen-induced plant volatiles for real-time crop monitoring
Researcher (PI) Theodoor Turlings
Host Institution (HI) UNIVERSITE DE NEUCHATEL
Country Switzerland
Call Details Advanced Grant (AdG), LS9, ERC-2017-ADG
Summary Plants typically release large quantities of volatiles in response to attack by herbivores or pathogens. I may claim to have contributed to various breakthroughs in this research field, including the discovery that the volatile blends induced by different attackers are astonishingly specific, resulting in characteristic, readily distinguishable odour blends. Using maize as our model plant, I wish to take several leaps forward in our understanding of this signal specificity and use this knowledge to develop sensors for the real-time detection of crop pests and diseases. For this, three interconnected work-packages will aim to:
• Develop chemical analytical techniques and statistical models to decipher the odorous vocabulary of plants, and to create a complete inventory of “odour-prints” for a wide range of herbivore-plant and pathogen-plant combinations, including simultaneous infestations.
• Develop and optimize nano-mechanical sensors for the detection of specific plant volatile mixtures. For this, we will initially adapt a prototype sensor that has been successfully developed for the detection of cancer-related volatiles in human breath.
• Genetically manipulate maize plants to release a unique blend of root-produced volatiles upon herbivory. For this, we will engineer gene cassettes that combine recently identified P450 (CYP) genes from poplar with inducible, root-specific promoters from maize. This will result in maize plants that, in response to pest attack, release easy-to-detect aldoximes and nitriles from their roots.
In short, by investigating and manipulating the specificity of inducible odour blends we will generate the necessary knowhow to develop a novel odour-detection device. The envisioned sensor technology will permit real-time monitoring of the pests and enable farmers to apply crop protection treatments at the right time and in the right place.
Summary
Plants typically release large quantities of volatiles in response to attack by herbivores or pathogens. I may claim to have contributed to various breakthroughs in this research field, including the discovery that the volatile blends induced by different attackers are astonishingly specific, resulting in characteristic, readily distinguishable odour blends. Using maize as our model plant, I wish to take several leaps forward in our understanding of this signal specificity and use this knowledge to develop sensors for the real-time detection of crop pests and diseases. For this, three interconnected work-packages will aim to:
• Develop chemical analytical techniques and statistical models to decipher the odorous vocabulary of plants, and to create a complete inventory of “odour-prints” for a wide range of herbivore-plant and pathogen-plant combinations, including simultaneous infestations.
• Develop and optimize nano-mechanical sensors for the detection of specific plant volatile mixtures. For this, we will initially adapt a prototype sensor that has been successfully developed for the detection of cancer-related volatiles in human breath.
• Genetically manipulate maize plants to release a unique blend of root-produced volatiles upon herbivory. For this, we will engineer gene cassettes that combine recently identified P450 (CYP) genes from poplar with inducible, root-specific promoters from maize. This will result in maize plants that, in response to pest attack, release easy-to-detect aldoximes and nitriles from their roots.
In short, by investigating and manipulating the specificity of inducible odour blends we will generate the necessary knowhow to develop a novel odour-detection device. The envisioned sensor technology will permit real-time monitoring of the pests and enable farmers to apply crop protection treatments at the right time and in the right place.
Max ERC Funding
2 498 086 €
Duration
Start date: 2018-09-01, End date: 2023-08-31
Project acronym ALICE
Project Strange Mirrors, Unsuspected Lessons: Leading Europe to a new way of sharing the world experiences
Researcher (PI) Boaventura De Sousa Santos
Host Institution (HI) CENTRO DE ESTUDOS SOCIAIS
Country Portugal
Call Details Advanced Grant (AdG), SH2, ERC-2010-AdG_20100407
Summary Europe sits uncomfortably on the idea that there are no political and cultural alternatives credible enough to respond to the current uneasiness or malaise caused by both a world that is more and more non-European and a Europe that increasingly questions what is European about itself. This project will develop a new grounded theoretical paradigm for contemporary Europe based on two key ideas: the understanding of the world by far exceeds the European understanding of the world; social, political and institutional transformation in Europe may benefit from innovations taking place in regions and countries with which Europe is increasingly interdependent. I will pursue this objective focusing on four main interconnected topics: democratizing democracy, intercultural constitutionalism, the other economy, human rights (right to health in particular).
In a sense that the European challenges are unique but, in one way or another, are being experienced in different corners of the world. The novelty resides in bringing new ideas and experiences into the European conversation, show their relevance to our current uncertainties and aspirations and thereby contribute to face them with new intellectual and political resources. The usefulness and relevance of non-European conceptions and experiences un-thinking the conventional knowledge through two epistemological devices I have developed: the ecology of knowledges and intercultural translation. By resorting to them I will show that there are alternatives but they cannot be made credible and powerful if we go on relying on the modes of theoretical and political thinking that have dominated so far. In other words, the claim put forward by and worked through this project is that in Europe we don’t need alternatives but rather an alternative thinking of alternatives.
Summary
Europe sits uncomfortably on the idea that there are no political and cultural alternatives credible enough to respond to the current uneasiness or malaise caused by both a world that is more and more non-European and a Europe that increasingly questions what is European about itself. This project will develop a new grounded theoretical paradigm for contemporary Europe based on two key ideas: the understanding of the world by far exceeds the European understanding of the world; social, political and institutional transformation in Europe may benefit from innovations taking place in regions and countries with which Europe is increasingly interdependent. I will pursue this objective focusing on four main interconnected topics: democratizing democracy, intercultural constitutionalism, the other economy, human rights (right to health in particular).
In a sense that the European challenges are unique but, in one way or another, are being experienced in different corners of the world. The novelty resides in bringing new ideas and experiences into the European conversation, show their relevance to our current uncertainties and aspirations and thereby contribute to face them with new intellectual and political resources. The usefulness and relevance of non-European conceptions and experiences un-thinking the conventional knowledge through two epistemological devices I have developed: the ecology of knowledges and intercultural translation. By resorting to them I will show that there are alternatives but they cannot be made credible and powerful if we go on relying on the modes of theoretical and political thinking that have dominated so far. In other words, the claim put forward by and worked through this project is that in Europe we don’t need alternatives but rather an alternative thinking of alternatives.
Max ERC Funding
2 423 140 €
Duration
Start date: 2011-07-01, End date: 2016-12-31
Project acronym AMIMOS
Project Agile MIMO Systems for Communications, Biomedicine, and Defense
Researcher (PI) Bjorn Ottersten
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Country Sweden
Call Details Advanced Grant (AdG), PE7, ERC-2008-AdG
Summary This proposal targets the emerging frontier research field of multiple-input multiple-output (MIMO) systems along with several innovative and somewhat unconventional applications of such systems. The use of arrays of transmitters and receivers will have a profound impact on future medical imaging/therapy systems, radar systems, and radio communication networks. Multiple transmitters provide a tremendous versatility and allow waveforms to be adapted temporally and spatially to environmental conditions. This is useful for individually tailored illumination of human tissue in biomedical imaging or ultrasound therapy. In radar systems, multiple transmit beams can be formed simultaneously via separate waveform designs allowing accurate target classification. In a wireless communication system, multiple communication signals can be directed to one or more users at the same time on the same frequency carrier. In addition, multiple receivers can be used in the above applications to provide increased detection performance, interference rejection, and improved estimation accuracy. The joint modelling, analysis, and design of these multidimensional transmit and receive schemes form the core of this research proposal. Ultimately, our research aims at developing the fundamental tools that will allow the design of wireless communication systems with an order-of-magnitude higher capacity at a lower cost than today; of ultrasound therapy systems maximizing delivered power while reducing treatment duration and unwanted illumination; and of distributed aperture multi-beam radars allowing more effective target location, identification, and classification. Europe has several successful industries that are active in biomedical imaging/therapy, radar systems, and wireless communications. The future success of these sectors critically depends on the ability to innovate and integrate new technology.
Summary
This proposal targets the emerging frontier research field of multiple-input multiple-output (MIMO) systems along with several innovative and somewhat unconventional applications of such systems. The use of arrays of transmitters and receivers will have a profound impact on future medical imaging/therapy systems, radar systems, and radio communication networks. Multiple transmitters provide a tremendous versatility and allow waveforms to be adapted temporally and spatially to environmental conditions. This is useful for individually tailored illumination of human tissue in biomedical imaging or ultrasound therapy. In radar systems, multiple transmit beams can be formed simultaneously via separate waveform designs allowing accurate target classification. In a wireless communication system, multiple communication signals can be directed to one or more users at the same time on the same frequency carrier. In addition, multiple receivers can be used in the above applications to provide increased detection performance, interference rejection, and improved estimation accuracy. The joint modelling, analysis, and design of these multidimensional transmit and receive schemes form the core of this research proposal. Ultimately, our research aims at developing the fundamental tools that will allow the design of wireless communication systems with an order-of-magnitude higher capacity at a lower cost than today; of ultrasound therapy systems maximizing delivered power while reducing treatment duration and unwanted illumination; and of distributed aperture multi-beam radars allowing more effective target location, identification, and classification. Europe has several successful industries that are active in biomedical imaging/therapy, radar systems, and wireless communications. The future success of these sectors critically depends on the ability to innovate and integrate new technology.
Max ERC Funding
1 872 720 €
Duration
Start date: 2009-01-01, End date: 2013-12-31
Project acronym ANALYTICAL SOCIOLOGY
Project Analytical Sociology: Theoretical Developments and Empirical Research
Researcher (PI) Mats Peter Hedstroem
Host Institution (HI) LINKOPINGS UNIVERSITET
Country Sweden
Call Details Advanced Grant (AdG), SH2, ERC-2012-ADG_20120411
Summary This proposal outlines a highly ambitious and path-breaking research program. Through a tightly integrated package of basic theoretical work, strategic empirical research projects, international workshops, and a large number of publications in leading journals, the research program seeks to move sociology in a more analytical direction.
One part of the research program focuses on the epistemological and methodological foundations of analytical sociology, an approach to sociological theory and research that currently receives considerable attention in the international scholarly community. This work will be organized around two core themes: (1) the principles of mechanism-based explanations and (2) the micro-macro link.
The empirical research analyzes in great detail the ethnic, gender, and socio-economic segregation of key interaction domains in Sweden using the approach of analytical sociology. The interaction domains focused upon are schools, workplaces and neighborhoods; domains where people spend a considerable part of their time, where much of the social interaction between people takes place, where identities are formed, and where important resources are distributed.
Large-scale longitudinal micro data on the entire Swedish population, unique longitudinal data on social networks within school classes, and various agent-based simulation techniques, are used to better understand the processes through which schools, workplaces and neighborhoods become segregated along various dimensions, how the domains interact with one another, and how the structure and extent of segregation affects diverse social and economic outcomes.
Summary
This proposal outlines a highly ambitious and path-breaking research program. Through a tightly integrated package of basic theoretical work, strategic empirical research projects, international workshops, and a large number of publications in leading journals, the research program seeks to move sociology in a more analytical direction.
One part of the research program focuses on the epistemological and methodological foundations of analytical sociology, an approach to sociological theory and research that currently receives considerable attention in the international scholarly community. This work will be organized around two core themes: (1) the principles of mechanism-based explanations and (2) the micro-macro link.
The empirical research analyzes in great detail the ethnic, gender, and socio-economic segregation of key interaction domains in Sweden using the approach of analytical sociology. The interaction domains focused upon are schools, workplaces and neighborhoods; domains where people spend a considerable part of their time, where much of the social interaction between people takes place, where identities are formed, and where important resources are distributed.
Large-scale longitudinal micro data on the entire Swedish population, unique longitudinal data on social networks within school classes, and various agent-based simulation techniques, are used to better understand the processes through which schools, workplaces and neighborhoods become segregated along various dimensions, how the domains interact with one another, and how the structure and extent of segregation affects diverse social and economic outcomes.
Max ERC Funding
1 745 098 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym BARRAGE
Project Cell compartmentalization, individuation and diversity
Researcher (PI) Yves Barral
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Advanced Grant (AdG), LS3, ERC-2009-AdG
Summary Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.
Summary
Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.
Max ERC Funding
2 200 000 €
Duration
Start date: 2010-05-01, End date: 2015-04-30
Project acronym BIRD
Project Bimanual Manipulation of Rigid and Deformable Objects
Researcher (PI) Danica KRAGIC JENSFELT
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Country Sweden
Call Details Advanced Grant (AdG), PE7, ERC-2019-ADG
Summary All day long, our fingers touch, grasp and move objects in various media such as air, water, oil. We do this almost effortlessly - it feels like we do not spend time planning and reflecting over what our hands and fingers do or how the continuous integration of various sensory modalities such as vision, touch, proprioception, hearing help us to outperform any other biological system in the variety of the interaction tasks that we can execute. Largely overlooked, and perhaps most fascinating is the ease with which we perform these interactions resulting in a belief that these are also easy to accomplish in artificial systems such as robots. However, there are still no robots that can easily hand-wash dishes, button a shirt or peel a potato. Our claim is that this is fundamentally a problem of appropriate representation or parameterization. When interacting with objects, the robot needs to consider geometric, topological, and physical properties of objects. This can be done either explicitly, by modeling and representing these properties, or implicitly, by learning them from data. The main scientific objective of this project is to create new informative and compact representations of deformable objects that incorporate both analytical and learning-based approaches and encode geometric, topological, and physical information about the robot, the object, and the environment. We will do this in the context of challenging multimodal, bimanual object interaction tasks. The focus will be on physical interaction with deformable objects using multimodal feedback. To meet these objectives, we will use theoretical and computational methods together with rigorous experimental evaluation to model skilled sensorimotor behavior in bimanual robot systems.
Summary
All day long, our fingers touch, grasp and move objects in various media such as air, water, oil. We do this almost effortlessly - it feels like we do not spend time planning and reflecting over what our hands and fingers do or how the continuous integration of various sensory modalities such as vision, touch, proprioception, hearing help us to outperform any other biological system in the variety of the interaction tasks that we can execute. Largely overlooked, and perhaps most fascinating is the ease with which we perform these interactions resulting in a belief that these are also easy to accomplish in artificial systems such as robots. However, there are still no robots that can easily hand-wash dishes, button a shirt or peel a potato. Our claim is that this is fundamentally a problem of appropriate representation or parameterization. When interacting with objects, the robot needs to consider geometric, topological, and physical properties of objects. This can be done either explicitly, by modeling and representing these properties, or implicitly, by learning them from data. The main scientific objective of this project is to create new informative and compact representations of deformable objects that incorporate both analytical and learning-based approaches and encode geometric, topological, and physical information about the robot, the object, and the environment. We will do this in the context of challenging multimodal, bimanual object interaction tasks. The focus will be on physical interaction with deformable objects using multimodal feedback. To meet these objectives, we will use theoretical and computational methods together with rigorous experimental evaluation to model skilled sensorimotor behavior in bimanual robot systems.
Max ERC Funding
2 424 186 €
Duration
Start date: 2020-09-01, End date: 2025-08-31
Project acronym BOTMED
Project Microrobotics and Nanomedicine
Researcher (PI) Bradley James Nelson
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Country Switzerland
Call Details Advanced Grant (AdG), PE7, ERC-2010-AdG_20100224
Summary The introduction of minimally invasive surgery in the 1980’s created a paradigm shift in surgical procedures. Health care is now in a position to make a more dramatic leap by integrating newly developed wireless microrobotic technologies with nanomedicine to perform precisely targeted, localized endoluminal techniques. Devices capable of entering the human body through natural orifices or small incisions to deliver drugs, perform diagnostic procedures, and excise and repair tissue will be used. These new procedures will result in less trauma to the patient and faster recovery times, and will enable new therapies that have not yet been conceived. In order to realize this, many new technologies must be developed and synergistically integrated, and medical therapies for which the technology will prove successful must be aggressively pursued.
This proposed project will result in the realization of animal trials in which wireless microrobotic devices will be used to investigate a variety of extremely delicate ophthalmic therapies. The therapies to be pursued include the delivery of tissue plasminogen activator (t-PA) to blocked retinal veins, the peeling of epiretinal membranes from the retina, and the development of diagnostic procedures based on mapping oxygen concentration at the vitreous-retina interface. With successful animal trials, a path to human trials and commercialization will follow. Clearly, many systems in the body have the potential to benefit from the endoluminal technologies that this project considers, including the digestive system, the circulatory system, the urinary system, the central nervous system, the respiratory system, the female reproductive system and even the fetus. Microrobotic retinal therapies will greatly illuminate the potential that the integration of microrobotics and nanomedicine holds for society, and greatly accelerate this trend in Europe.
Summary
The introduction of minimally invasive surgery in the 1980’s created a paradigm shift in surgical procedures. Health care is now in a position to make a more dramatic leap by integrating newly developed wireless microrobotic technologies with nanomedicine to perform precisely targeted, localized endoluminal techniques. Devices capable of entering the human body through natural orifices or small incisions to deliver drugs, perform diagnostic procedures, and excise and repair tissue will be used. These new procedures will result in less trauma to the patient and faster recovery times, and will enable new therapies that have not yet been conceived. In order to realize this, many new technologies must be developed and synergistically integrated, and medical therapies for which the technology will prove successful must be aggressively pursued.
This proposed project will result in the realization of animal trials in which wireless microrobotic devices will be used to investigate a variety of extremely delicate ophthalmic therapies. The therapies to be pursued include the delivery of tissue plasminogen activator (t-PA) to blocked retinal veins, the peeling of epiretinal membranes from the retina, and the development of diagnostic procedures based on mapping oxygen concentration at the vitreous-retina interface. With successful animal trials, a path to human trials and commercialization will follow. Clearly, many systems in the body have the potential to benefit from the endoluminal technologies that this project considers, including the digestive system, the circulatory system, the urinary system, the central nervous system, the respiratory system, the female reproductive system and even the fetus. Microrobotic retinal therapies will greatly illuminate the potential that the integration of microrobotics and nanomedicine holds for society, and greatly accelerate this trend in Europe.
Max ERC Funding
2 498 044 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym CellularBiographies
Project Global views of cell type specification and differentiation
Researcher (PI) Alexander Schier
Host Institution (HI) UNIVERSITAT BASEL
Country Switzerland
Call Details Advanced Grant (AdG), LS3, ERC-2018-ADG
Summary Each cell in our body has a specific biography that is defined by its pedigree relationship with other cells (lineage) and by its history of gene expression (trajectory). A fundamental question in cellular and developmental biology has been how the lineage and trajectory of a cell lead to its specification and differentiation. Remarkable progress in genome editing and single-cell sequencing has generated the opportunity to understand this process at global scales and single-cell resolution. We have recently developed methods to reconstruct the cellular ancestry and transcriptional trajectories of cells during embryogenesis. The resulting lineage and trajectory trees can be analyzed to gain comprehensive views of how cellular diversity arises and how differentiation leads to physiologically specialized cell types. To generate such global views of cellular development, we will: 1. Define the cellular diversity and gene expression trajectories during zebrafish embryogenesis and organogenesis. Trajectory trees will be generated from scRNA-seq data and analyzed to reconstruct the gene expression pathways underlying fate specification. 2. Reveal the relationships between lineage and transcriptional trajectories during fate specification. Lineage trees will be generated by marking cells via genome editing and combined with trajectory trees to reveal the cellular paths towards fate specification. 3. Discover the gene expression cascades that remodel cells into physiologically functional types. Cell biological modules will be identified by comparing gene enrichment in differentiation trajectories and reveal the specialized and shared mechanisms of differentiation. These studies will help provide the first comprehensive and global view of the trajectories and lineages underlying vertebrate development. Our focus is on the zebrafish model system, but the data and concepts developed in this project will be applicable to other developmental and cellular systems.
Summary
Each cell in our body has a specific biography that is defined by its pedigree relationship with other cells (lineage) and by its history of gene expression (trajectory). A fundamental question in cellular and developmental biology has been how the lineage and trajectory of a cell lead to its specification and differentiation. Remarkable progress in genome editing and single-cell sequencing has generated the opportunity to understand this process at global scales and single-cell resolution. We have recently developed methods to reconstruct the cellular ancestry and transcriptional trajectories of cells during embryogenesis. The resulting lineage and trajectory trees can be analyzed to gain comprehensive views of how cellular diversity arises and how differentiation leads to physiologically specialized cell types. To generate such global views of cellular development, we will: 1. Define the cellular diversity and gene expression trajectories during zebrafish embryogenesis and organogenesis. Trajectory trees will be generated from scRNA-seq data and analyzed to reconstruct the gene expression pathways underlying fate specification. 2. Reveal the relationships between lineage and transcriptional trajectories during fate specification. Lineage trees will be generated by marking cells via genome editing and combined with trajectory trees to reveal the cellular paths towards fate specification. 3. Discover the gene expression cascades that remodel cells into physiologically functional types. Cell biological modules will be identified by comparing gene enrichment in differentiation trajectories and reveal the specialized and shared mechanisms of differentiation. These studies will help provide the first comprehensive and global view of the trajectories and lineages underlying vertebrate development. Our focus is on the zebrafish model system, but the data and concepts developed in this project will be applicable to other developmental and cellular systems.
Max ERC Funding
2 411 440 €
Duration
Start date: 2020-01-01, End date: 2024-12-31
Project acronym CENDUP
Project Decoding the mechanisms of centrosome duplication
Researcher (PI) Pierre Goenczy
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Country Switzerland
Call Details Advanced Grant (AdG), LS3, ERC-2008-AdG
Summary Centrosome duplication entails the formation of a single procentriole next to each centriole once per cell cycle. The mechanisms governing procentriole formation are poorly understood and constitute a fundamental open question in cell biology. We will launch an innovative multidisciplinary research program to gain significant insight into these mechanisms using C. elegans and human cells. This research program is also expected to have a significant impact by contributing important novel assays to the field. Six specific aims will be pursued: 1) SAS-6 as a ZYG-1 substrate: mechanisms of procentriole formation in C. elegans. We will test in vivo the consequence of SAS-6 phosphorylation by ZYG-1. 2) Biochemical and structural analysis of SAS-6-containing macromolecular complexes (SAMACs). We will isolate and characterize SAMACs from C. elegans embryos and human cells, and analyze their structure using single-particle electron microscopy. 3) Novel cell-free assay for procentriole formation in human cells. We will develop such an assay and use it to test whether SAMACs can direct procentriole formation and whether candidate proteins are needed at centrioles or in the cytoplasm. 4) Mapping interactions between centriolar proteins in live human cells. We will use chemical methods developed by our collaborators to probe interactions between HsSAS-6 and centriolar proteins in a time- and space-resolved manner. 5) Functional genomic and chemical genetic screens in human cells. We will conduct high-throughput fluorescence-based screens in human cells to identify novel genes required for procentriole formation and small molecule inhibitors of this process. 6) Mechanisms underlying differential centriolar maintenance in the germline. In C. elegans, we will characterize how the sas-1 locus is required for centriole maintenance during spermatogenesis, as well as analyze centriole elimination during oogenesis and identify components needed for this process
Summary
Centrosome duplication entails the formation of a single procentriole next to each centriole once per cell cycle. The mechanisms governing procentriole formation are poorly understood and constitute a fundamental open question in cell biology. We will launch an innovative multidisciplinary research program to gain significant insight into these mechanisms using C. elegans and human cells. This research program is also expected to have a significant impact by contributing important novel assays to the field. Six specific aims will be pursued: 1) SAS-6 as a ZYG-1 substrate: mechanisms of procentriole formation in C. elegans. We will test in vivo the consequence of SAS-6 phosphorylation by ZYG-1. 2) Biochemical and structural analysis of SAS-6-containing macromolecular complexes (SAMACs). We will isolate and characterize SAMACs from C. elegans embryos and human cells, and analyze their structure using single-particle electron microscopy. 3) Novel cell-free assay for procentriole formation in human cells. We will develop such an assay and use it to test whether SAMACs can direct procentriole formation and whether candidate proteins are needed at centrioles or in the cytoplasm. 4) Mapping interactions between centriolar proteins in live human cells. We will use chemical methods developed by our collaborators to probe interactions between HsSAS-6 and centriolar proteins in a time- and space-resolved manner. 5) Functional genomic and chemical genetic screens in human cells. We will conduct high-throughput fluorescence-based screens in human cells to identify novel genes required for procentriole formation and small molecule inhibitors of this process. 6) Mechanisms underlying differential centriolar maintenance in the germline. In C. elegans, we will characterize how the sas-1 locus is required for centriole maintenance during spermatogenesis, as well as analyze centriole elimination during oogenesis and identify components needed for this process
Max ERC Funding
2 004 155 €
Duration
Start date: 2009-04-01, End date: 2014-03-31
Project acronym CENFOR
Project Dissecting the mechanisms governing centriole formation
Researcher (PI) Pierre Goenczy
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Country Switzerland
Call Details Advanced Grant (AdG), LS3, ERC-2013-ADG
Summary "Centrioles are critical for the formation of cilia, flagella and centrosomes, as well as for human health. The mechanisms governing centriole formation constitute a long-standing question in cell biology. We will pursue an innovative multidisciplinary research program to gain further insight into these mechanisms, using human cells, C. elegans and Trichonympha as model systems. This program is expected to also have a major impact by contributing a novel cell free assay to the field, thus paving the way towards making synthetic centrioles. Six specific aims will be pursued:
1) Deciphering HsSAS-6/STIL distribution and dynamics. We will use super-resolution microscopy, molecular counting, photoconversion and FCS to further characterize these two key components required for centriole formation in human cells.
2) The SAS-6 ring model as a tool to redirect centriole organization. Utilizing predictions from the SAS-6 ring model, we will assay the consequences for centrioles and cilia of altering the diameter and symmetry of the structure.
3) Determining the architecture of C. elegans centrioles. We will conduct molecular counting and cryo-ET of purified C. elegans centrioles to determine if they contain a spiral or a cartwheel, as well as identify SAS-6-interacting components.
4) Comprehensive 3D map and proteomics of Trichonympha centriole. We will obtain a ~35 Å 3D map of the complete T. agilis centriole, perform proteomic analysis to identify its constituents and test their function using RNAi.
5) Regulation of cartwheel height and centriole length. We will explore whether cartwheel height is set by SAS-6 proteins and perform screens in human cells to identify novel components regulating cartwheel height and centriole length.
6) Novel cell free assay for cartwheel assembly and centriole formation. Using SAS-6 proteins on a lipid monolayer as starting point, we will develop and utilize a cell-free assay to reconstitute cartwheel assembly and centriole format"
Summary
"Centrioles are critical for the formation of cilia, flagella and centrosomes, as well as for human health. The mechanisms governing centriole formation constitute a long-standing question in cell biology. We will pursue an innovative multidisciplinary research program to gain further insight into these mechanisms, using human cells, C. elegans and Trichonympha as model systems. This program is expected to also have a major impact by contributing a novel cell free assay to the field, thus paving the way towards making synthetic centrioles. Six specific aims will be pursued:
1) Deciphering HsSAS-6/STIL distribution and dynamics. We will use super-resolution microscopy, molecular counting, photoconversion and FCS to further characterize these two key components required for centriole formation in human cells.
2) The SAS-6 ring model as a tool to redirect centriole organization. Utilizing predictions from the SAS-6 ring model, we will assay the consequences for centrioles and cilia of altering the diameter and symmetry of the structure.
3) Determining the architecture of C. elegans centrioles. We will conduct molecular counting and cryo-ET of purified C. elegans centrioles to determine if they contain a spiral or a cartwheel, as well as identify SAS-6-interacting components.
4) Comprehensive 3D map and proteomics of Trichonympha centriole. We will obtain a ~35 Å 3D map of the complete T. agilis centriole, perform proteomic analysis to identify its constituents and test their function using RNAi.
5) Regulation of cartwheel height and centriole length. We will explore whether cartwheel height is set by SAS-6 proteins and perform screens in human cells to identify novel components regulating cartwheel height and centriole length.
6) Novel cell free assay for cartwheel assembly and centriole formation. Using SAS-6 proteins on a lipid monolayer as starting point, we will develop and utilize a cell-free assay to reconstitute cartwheel assembly and centriole format"
Max ERC Funding
2 499 270 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
