Project acronym 2DQP
Project Two-dimensional quantum photonics
Researcher (PI) Brian David GERARDOT
Host Institution (HI) HERIOT-WATT UNIVERSITY
Call Details Consolidator Grant (CoG), PE3, ERC-2016-COG
Summary Quantum optics, the study of how discrete packets of light (photons) and matter interact, has led to the development of remarkable new technologies which exploit the bizarre properties of quantum mechanics. These quantum technologies are primed to revolutionize the fields of communication, information processing, and metrology in the coming years. Similar to contemporary technologies, the future quantum machinery will likely consist of a semiconductor platform to create and process the quantum information. However, to date the demanding requirements on a quantum photonic platform have yet to be satisfied with conventional bulk (three-dimensional) semiconductors.
To surmount these well-known obstacles, a new paradigm in quantum photonics is required. Initiated by the recent discovery of single photon emitters in atomically flat (two-dimensional) semiconducting materials, 2DQP aims to be at the nucleus of a new approach by realizing quantum optics with ultra-stable (coherent) quantum states integrated into devices with electronic and photonic functionality. We will characterize, identify, engineer, and coherently manipulate localized quantum states in this two-dimensional quantum photonic platform. A vital component of 2DQP’s vision is to go beyond the fundamental science and achieve the ideal solid-state single photon device yielding perfect extraction - 100% efficiency - of on-demand indistinguishable single photons. Finally, we will exploit this ideal device to implement the critical building block for a photonic quantum computer.
Summary
Quantum optics, the study of how discrete packets of light (photons) and matter interact, has led to the development of remarkable new technologies which exploit the bizarre properties of quantum mechanics. These quantum technologies are primed to revolutionize the fields of communication, information processing, and metrology in the coming years. Similar to contemporary technologies, the future quantum machinery will likely consist of a semiconductor platform to create and process the quantum information. However, to date the demanding requirements on a quantum photonic platform have yet to be satisfied with conventional bulk (three-dimensional) semiconductors.
To surmount these well-known obstacles, a new paradigm in quantum photonics is required. Initiated by the recent discovery of single photon emitters in atomically flat (two-dimensional) semiconducting materials, 2DQP aims to be at the nucleus of a new approach by realizing quantum optics with ultra-stable (coherent) quantum states integrated into devices with electronic and photonic functionality. We will characterize, identify, engineer, and coherently manipulate localized quantum states in this two-dimensional quantum photonic platform. A vital component of 2DQP’s vision is to go beyond the fundamental science and achieve the ideal solid-state single photon device yielding perfect extraction - 100% efficiency - of on-demand indistinguishable single photons. Finally, we will exploit this ideal device to implement the critical building block for a photonic quantum computer.
Max ERC Funding
1 999 135 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym 3D-BioMat
Project Deciphering biomineralization mechanisms through 3D explorations of mesoscale crystalline structure in calcareous biomaterials
Researcher (PI) VIRGINIE CHAMARD
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), PE3, ERC-2016-COG
Summary The fundamental 3D-BioMat project aims at providing a biomineralization model to explain the formation of microscopic calcareous single-crystals produced by living organisms. Although these crystals present a wide variety of shapes, associated to various organic materials, the observation of a nanoscale granular structure common to almost all calcareous crystallizing organisms, associated to an extended crystalline coherence, underlies a generic biomineralization and assembly process. A key to building realistic scenarios of biomineralization is to reveal the crystalline architecture, at the mesoscale, (i. e., over a few granules), which none of the existing nano-characterization tools is able to provide.
3D-BioMat is based on the recognized PI’s expertise in the field of synchrotron coherent x-ray diffraction microscopy. It will extend the PI’s disruptive pioneering microscopy formalism, towards an innovative high-throughput approach able at giving access to the 3D mesoscale image of the crystalline properties (crystal-line coherence, crystal plane tilts and strains) with the required flexibility, nanoscale resolution, and non-invasiveness.
This achievement will be used to timely reveal the generics of the mesoscale crystalline structure through the pioneering explorations of a vast variety of crystalline biominerals produced by the famous Pinctada mar-garitifera oyster shell, and thereby build a realistic biomineralization scenario.
The inferred biomineralization pathways, including both physico-chemical pathways and biological controls, will ultimately be validated by comparing the mesoscale structures produced by biomimetic samples with the biogenic ones. Beyond deciphering one of the most intriguing questions of material nanosciences, 3D-BioMat may contribute to new climate models, pave the way for new routes in material synthesis and supply answers to the pearl-culture calcification problems.
Summary
The fundamental 3D-BioMat project aims at providing a biomineralization model to explain the formation of microscopic calcareous single-crystals produced by living organisms. Although these crystals present a wide variety of shapes, associated to various organic materials, the observation of a nanoscale granular structure common to almost all calcareous crystallizing organisms, associated to an extended crystalline coherence, underlies a generic biomineralization and assembly process. A key to building realistic scenarios of biomineralization is to reveal the crystalline architecture, at the mesoscale, (i. e., over a few granules), which none of the existing nano-characterization tools is able to provide.
3D-BioMat is based on the recognized PI’s expertise in the field of synchrotron coherent x-ray diffraction microscopy. It will extend the PI’s disruptive pioneering microscopy formalism, towards an innovative high-throughput approach able at giving access to the 3D mesoscale image of the crystalline properties (crystal-line coherence, crystal plane tilts and strains) with the required flexibility, nanoscale resolution, and non-invasiveness.
This achievement will be used to timely reveal the generics of the mesoscale crystalline structure through the pioneering explorations of a vast variety of crystalline biominerals produced by the famous Pinctada mar-garitifera oyster shell, and thereby build a realistic biomineralization scenario.
The inferred biomineralization pathways, including both physico-chemical pathways and biological controls, will ultimately be validated by comparing the mesoscale structures produced by biomimetic samples with the biogenic ones. Beyond deciphering one of the most intriguing questions of material nanosciences, 3D-BioMat may contribute to new climate models, pave the way for new routes in material synthesis and supply answers to the pearl-culture calcification problems.
Max ERC Funding
1 966 429 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym BG-BB-AS
Project Birational Geometry, B-branes and Artin Stacks
Researcher (PI) Edward Paul Segal
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Consolidator Grant (CoG), PE1, ERC-2016-COG
Summary Derived categories of coherent sheaves on a variety are a fundamental tool in algebraic geometry. They also arise in String Theory, as the category of B-branes in a quantum field theory whose target space is the variety. This connection to physics has been extraordinarily fruitful, providing deep insights and conjectures.
An Artin stack is a sophisticated generalization of a variety, they encode the idea of equivariant geometry. A simple example is a vector space carrying a linear action of a Lie group. In String Theory this data defines a Gauged Linear Sigma Model, which is a basic tool in the subject. A GLSM should also give rise to a category of B-branes, but surprisingly it is not yet understood what this should be. An overarching goal of this project is to develop an understanding of this category (more accurately, system of categories), and to extend this understanding to more general Artin stacks.
The basic importance of this question is that in certain limits a GLSM reduces to a sigma model, whose target is a quotient of the vector space by the group. This quotient must be taken using Geometric Invariant Theory. Thus this project is intimately connected with the question of how derived categories change under variation-of-GIT, and birational maps in general.
For GLSMs with abelian groups this approach has already produced spectacular results, in the non-abelian case we understand only a few remarkable examples. We will develop these examples into a wide-ranging general theory.
Our key objectives are to:
- Provide powerful new tools for controlling the behaviour of derived categories under birational maps.
- Understand the category of B-branes on a large class of Artin stacks.
- Prove and apply a striking new duality between GLSMs.
- Construct completely new symmetries of derived categories.
Summary
Derived categories of coherent sheaves on a variety are a fundamental tool in algebraic geometry. They also arise in String Theory, as the category of B-branes in a quantum field theory whose target space is the variety. This connection to physics has been extraordinarily fruitful, providing deep insights and conjectures.
An Artin stack is a sophisticated generalization of a variety, they encode the idea of equivariant geometry. A simple example is a vector space carrying a linear action of a Lie group. In String Theory this data defines a Gauged Linear Sigma Model, which is a basic tool in the subject. A GLSM should also give rise to a category of B-branes, but surprisingly it is not yet understood what this should be. An overarching goal of this project is to develop an understanding of this category (more accurately, system of categories), and to extend this understanding to more general Artin stacks.
The basic importance of this question is that in certain limits a GLSM reduces to a sigma model, whose target is a quotient of the vector space by the group. This quotient must be taken using Geometric Invariant Theory. Thus this project is intimately connected with the question of how derived categories change under variation-of-GIT, and birational maps in general.
For GLSMs with abelian groups this approach has already produced spectacular results, in the non-abelian case we understand only a few remarkable examples. We will develop these examples into a wide-ranging general theory.
Our key objectives are to:
- Provide powerful new tools for controlling the behaviour of derived categories under birational maps.
- Understand the category of B-branes on a large class of Artin stacks.
- Prove and apply a striking new duality between GLSMs.
- Construct completely new symmetries of derived categories.
Max ERC Funding
1 358 925 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym C18Signaling
Project Regulation of Cellular Growth and Metabolism by C18:0
Researcher (PI) Aurelio TELEMAN
Host Institution (HI) DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Call Details Consolidator Grant (CoG), LS3, ERC-2016-COG
Summary My lab studies how cells regulate their growth and metabolism during normal development and in disease. Recent work in my lab, published last year in Nature, identified the metabolite stearic acid (C18:0) as a novel regulator of mitochondrial function. We showed that dietary C18:0 acts via a novel signaling route whereby it covalently modifies the cell-surface Transferrin Receptor (TfR1) to regulate mitochondrial morphology. We found that modification of TfR1 by C18:0 ('stearoylation') is analogous to protein palmitoylation by C16:0 - it is a covalent thio-ester link and requires a transferase enzyme. This work made two conceptual contributions. 1) It uncovered a novel signaling route regulating mitochondrial function. 2) Relevant to this grant application, we found by mass spectrometry multiple other proteins that are stearoylated in mammalian cells. This thereby opens a new avenue of research, suggesting that C18:0 signals via several target proteins to regulate cellular growth and metabolism. I propose here to study this C18:0 signaling.
To study C18:0 signaling we will exploit tools recently developed in my lab to 1) identify as complete a set as possible of proteins that are stearoylated in human and Drosophila cells, thereby characterizing the cellular 'stearylome', 2) study how stearoylation affects the molecular function of these target proteins, and thereby cellular growth and metabolism, and 3) study how stearoylation is added, and possibly removed, from target proteins.
This work will change the way we view C18:0 from simply being a metabolite to being an important dietary signaling molecule that links nutritional uptake to cellular physiology. Via unknown mechanisms, dietary C18:0 is clinically known to have special properties for cardiovascular risk. Hence this proposal, discovering how C18:0 signals to regulate cells, will have implications for both normal development and for disease.
Summary
My lab studies how cells regulate their growth and metabolism during normal development and in disease. Recent work in my lab, published last year in Nature, identified the metabolite stearic acid (C18:0) as a novel regulator of mitochondrial function. We showed that dietary C18:0 acts via a novel signaling route whereby it covalently modifies the cell-surface Transferrin Receptor (TfR1) to regulate mitochondrial morphology. We found that modification of TfR1 by C18:0 ('stearoylation') is analogous to protein palmitoylation by C16:0 - it is a covalent thio-ester link and requires a transferase enzyme. This work made two conceptual contributions. 1) It uncovered a novel signaling route regulating mitochondrial function. 2) Relevant to this grant application, we found by mass spectrometry multiple other proteins that are stearoylated in mammalian cells. This thereby opens a new avenue of research, suggesting that C18:0 signals via several target proteins to regulate cellular growth and metabolism. I propose here to study this C18:0 signaling.
To study C18:0 signaling we will exploit tools recently developed in my lab to 1) identify as complete a set as possible of proteins that are stearoylated in human and Drosophila cells, thereby characterizing the cellular 'stearylome', 2) study how stearoylation affects the molecular function of these target proteins, and thereby cellular growth and metabolism, and 3) study how stearoylation is added, and possibly removed, from target proteins.
This work will change the way we view C18:0 from simply being a metabolite to being an important dietary signaling molecule that links nutritional uptake to cellular physiology. Via unknown mechanisms, dietary C18:0 is clinically known to have special properties for cardiovascular risk. Hence this proposal, discovering how C18:0 signals to regulate cells, will have implications for both normal development and for disease.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym CellStructure
Project Structural cell biology in situ using superresolution microscopy
Researcher (PI) Jonas RIES
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Call Details Consolidator Grant (CoG), PE3, ERC-2016-COG
Summary Supra-molecular protein machineries control diverse cellular processes. Knowing their structural organization is crucial for understanding their function. As classical structural biology techniques are limited in studying such assemblies in their natural cellular environment, there is a critical methodological gap inhibiting a direct link between structure and function. Consequently, the structural intermediates underlying a full activity cycle of a large multi-protein complex have been impossible to visualize. Recent advances in fluorescence microscopy, in particular the development of groundbreaking superresolution microscopy (SRM) methods, can now help bridge this gap. With this interdisciplinary proposal, my group will develop unique and innovative optical, biological and computational imaging technologies to determine the structural organization of multi-protein assemblies in their functional cellular context.
We will reach this goal by developing a method to robustly measure the precise 3D arrangements of proteins in supra-molecular assemblies in situ with nanometer isotropic resolution based on supercritical-angle detection and by measuring their absolute stoichiometries with engineered counting standards. We will also develop new data analysis tools to statistically analyze such data, taking into account the functional cellular context measured with correlative superresolution and electron microscopy, multi-color SRM and molecular biology tools. We will apply these new methods to address key questions on endocytosis, a fundamental membrane trafficking process. Our aim is to determine a time-resolved 3D superresolution localization map of the yeast endocytic proteins during the major functional transitions and to integrate these data into a mechanistic model of endocytosis. Importantly, the methods we develop here can be applied to many other large protein-based machines, and thus have the potential to have high impact in other key areas of cell biology.
Summary
Supra-molecular protein machineries control diverse cellular processes. Knowing their structural organization is crucial for understanding their function. As classical structural biology techniques are limited in studying such assemblies in their natural cellular environment, there is a critical methodological gap inhibiting a direct link between structure and function. Consequently, the structural intermediates underlying a full activity cycle of a large multi-protein complex have been impossible to visualize. Recent advances in fluorescence microscopy, in particular the development of groundbreaking superresolution microscopy (SRM) methods, can now help bridge this gap. With this interdisciplinary proposal, my group will develop unique and innovative optical, biological and computational imaging technologies to determine the structural organization of multi-protein assemblies in their functional cellular context.
We will reach this goal by developing a method to robustly measure the precise 3D arrangements of proteins in supra-molecular assemblies in situ with nanometer isotropic resolution based on supercritical-angle detection and by measuring their absolute stoichiometries with engineered counting standards. We will also develop new data analysis tools to statistically analyze such data, taking into account the functional cellular context measured with correlative superresolution and electron microscopy, multi-color SRM and molecular biology tools. We will apply these new methods to address key questions on endocytosis, a fundamental membrane trafficking process. Our aim is to determine a time-resolved 3D superresolution localization map of the yeast endocytic proteins during the major functional transitions and to integrate these data into a mechanistic model of endocytosis. Importantly, the methods we develop here can be applied to many other large protein-based machines, and thus have the potential to have high impact in other key areas of cell biology.
Max ERC Funding
1 686 469 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym CholeraIndex
Project Pathoecology of Vibrio cholerae to better understand cholera index cases in endemic areas
Researcher (PI) Melanie BLOKESCH
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Consolidator Grant (CoG), LS6, ERC-2016-COG
Summary Cholera is one of the oldest infectious diseases known and remains a major burden in many developing countries. The World Health Organization estimates that up to 4 million cases of cholera occur annually. The transmission of cholera by contaminated water, particularly under epidemic conditions, was first reported in the 19th century. However, early volunteer studies suggested that an incredibly high infectious dose (ID) is required to produce disease symptoms, in contrast to most other intestinal pathogens. Therefore, the mechanism of infection of index cases at the onset of an outbreak is unclear. This proposal aims to fill this knowledge gap by studying how the environmental lifestyle of the causative agent of the disease, the bacterium Vibrio cholerae, may prime the pathogen for intestinal colonization. We hypothesize that one of the natural niches of the bacterium (chitinous surfaces) fosters biofilm formation and provides a competitive advantage over co-colonizing bacteria. As an adaptive trait, passage of chitin-attached sessile V. cholerae through the acidic environment of the human stomach might be vastly facilitated compared to planktonic bacteria. Moreover, interbacterial warfare exerted by V. cholerae on these biotic surfaces may help the pathogen overcome the colonization barrier imposed by the human microbiota upon ingestion. The mechanism by which V. cholerae leaves the sessile lifestyle and the regulatory circuits involved in this process will also be investigated in this project. In summary, our goal is to elucidate the environmental community structures of V. cholerae that may enhance transmissibility from the ecosystem to humans in endemic areas resulting in the infection of index cases.
Summary
Cholera is one of the oldest infectious diseases known and remains a major burden in many developing countries. The World Health Organization estimates that up to 4 million cases of cholera occur annually. The transmission of cholera by contaminated water, particularly under epidemic conditions, was first reported in the 19th century. However, early volunteer studies suggested that an incredibly high infectious dose (ID) is required to produce disease symptoms, in contrast to most other intestinal pathogens. Therefore, the mechanism of infection of index cases at the onset of an outbreak is unclear. This proposal aims to fill this knowledge gap by studying how the environmental lifestyle of the causative agent of the disease, the bacterium Vibrio cholerae, may prime the pathogen for intestinal colonization. We hypothesize that one of the natural niches of the bacterium (chitinous surfaces) fosters biofilm formation and provides a competitive advantage over co-colonizing bacteria. As an adaptive trait, passage of chitin-attached sessile V. cholerae through the acidic environment of the human stomach might be vastly facilitated compared to planktonic bacteria. Moreover, interbacterial warfare exerted by V. cholerae on these biotic surfaces may help the pathogen overcome the colonization barrier imposed by the human microbiota upon ingestion. The mechanism by which V. cholerae leaves the sessile lifestyle and the regulatory circuits involved in this process will also be investigated in this project. In summary, our goal is to elucidate the environmental community structures of V. cholerae that may enhance transmissibility from the ecosystem to humans in endemic areas resulting in the infection of index cases.
Max ERC Funding
1 999 988 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
Project acronym CHROMONUMBER
Project Chromosome number variations in vivo: probing mechanisms of genesis and elimination
Researcher (PI) Renata BASTO
Host Institution (HI) INSTITUT CURIE
Call Details Consolidator Grant (CoG), LS3, ERC-2016-COG
Summary How variations in whole chromosome number impact organism homeostasis remains an open question. Variations to the normal euploid genome content are frequently found in healthy animals and are thought to contribute with phenotypic variability in adverse situations. Yet they are also at the basis of several human diseases, including neuro-developmental disorders and cancer. Our preliminary data shows that physiological aneuploidy can be identified in certain cells during development. Moreover, we have observed that when induced through mutations, non-euploid cells are effectively eliminated from the cycling population. A quantitative view of the frequency of non-euploid karyotypes and the mechanisms underlying their genesis is lacking in the literature. Further, the tissue specific responses at play to eliminate non-euploid cells, when induced through mutations are not understood. The objectives of this proposal are to quantitatively assess the occurrence of physiological chromosome number variations gaining insight into mechanisms involved in generating it. Additionally, we will identify the tissue-specific pathways involved in maintaining organism homeostasis through the elimination of non-euploid cells. We will use a novel genetic approach to monitor individual chromosome loss at the level of the entire organism, combine it with quantitative methods and state-of-the art-microscopy, and focus on two model organisms - Drosophila and mouse - during development and adulthood. We predict that the findings resulting from this proposal will significantly impact the fields of cell, developmental and animal physiology, generating novel concepts that will bridge the existing gaps in the field, and expand our understanding of the links between karyotype variations, animal development and disease establishment.
Summary
How variations in whole chromosome number impact organism homeostasis remains an open question. Variations to the normal euploid genome content are frequently found in healthy animals and are thought to contribute with phenotypic variability in adverse situations. Yet they are also at the basis of several human diseases, including neuro-developmental disorders and cancer. Our preliminary data shows that physiological aneuploidy can be identified in certain cells during development. Moreover, we have observed that when induced through mutations, non-euploid cells are effectively eliminated from the cycling population. A quantitative view of the frequency of non-euploid karyotypes and the mechanisms underlying their genesis is lacking in the literature. Further, the tissue specific responses at play to eliminate non-euploid cells, when induced through mutations are not understood. The objectives of this proposal are to quantitatively assess the occurrence of physiological chromosome number variations gaining insight into mechanisms involved in generating it. Additionally, we will identify the tissue-specific pathways involved in maintaining organism homeostasis through the elimination of non-euploid cells. We will use a novel genetic approach to monitor individual chromosome loss at the level of the entire organism, combine it with quantitative methods and state-of-the art-microscopy, and focus on two model organisms - Drosophila and mouse - during development and adulthood. We predict that the findings resulting from this proposal will significantly impact the fields of cell, developmental and animal physiology, generating novel concepts that will bridge the existing gaps in the field, and expand our understanding of the links between karyotype variations, animal development and disease establishment.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym COMBAT
Project Clearance Of Microbial Biofilms by Advancing diagnostics and Therapy
Researcher (PI) Susanne Christiane Haeussler
Host Institution (HI) HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH
Call Details Consolidator Grant (CoG), LS6, ERC-2016-COG
Summary Every year chronic infections in patients due to biofilm formation of pathogenic bacteria are a multi-billion Euro burden to national healthcare systems. Despite improvements in technology and medical services, morbidity and mortality due to chronic infections have remained unchanged over the past decades. The emergence of a chronic infection disease burden calls for the development of modern diagnostics for biofilm resistance profiling and new therapeutic strategies to eradicate biofilm-associated infections. However, many unsuccessful attempts to address this need teach us that alternative perspectives are needed to meet the challenges.
The project is committed to develop innovative diagnostics and to strive for therapeutic solutions in patients suffering from biofilm-associated infections. The objective is to apply data-driven science to unlock the potential of microbial genomics. This new approach uses tools of advanced microbiological genomics and machine learning in genome-wide association studies on an existing unprecedentedly large dataset. This dataset has been generated in my group within the last five years and comprises sequence variation and gene expression information of a plethora of clinical Pseudomonas aeruginosa isolates. The wealth of patterns and characteristics of biofilm resistance are invisible at a smaller scale and will be interpreted within context and domain-specific knowledge.
The unique combination of basic molecular biology research, technology-driven approaches and data-driven science allows pioneer research dedicated to advance strategies to combat biofilm-associated infections. My approach does not only provide a prediction of biofilm resistance based on the bacteria´s genotype but also holds promise to transform treatment paradigms for the management of chronic infections and by interference with bacterial stress responses will promote the effectiveness of antimicrobials in clinical use to eradicate biofilm infections.
Summary
Every year chronic infections in patients due to biofilm formation of pathogenic bacteria are a multi-billion Euro burden to national healthcare systems. Despite improvements in technology and medical services, morbidity and mortality due to chronic infections have remained unchanged over the past decades. The emergence of a chronic infection disease burden calls for the development of modern diagnostics for biofilm resistance profiling and new therapeutic strategies to eradicate biofilm-associated infections. However, many unsuccessful attempts to address this need teach us that alternative perspectives are needed to meet the challenges.
The project is committed to develop innovative diagnostics and to strive for therapeutic solutions in patients suffering from biofilm-associated infections. The objective is to apply data-driven science to unlock the potential of microbial genomics. This new approach uses tools of advanced microbiological genomics and machine learning in genome-wide association studies on an existing unprecedentedly large dataset. This dataset has been generated in my group within the last five years and comprises sequence variation and gene expression information of a plethora of clinical Pseudomonas aeruginosa isolates. The wealth of patterns and characteristics of biofilm resistance are invisible at a smaller scale and will be interpreted within context and domain-specific knowledge.
The unique combination of basic molecular biology research, technology-driven approaches and data-driven science allows pioneer research dedicated to advance strategies to combat biofilm-associated infections. My approach does not only provide a prediction of biofilm resistance based on the bacteria´s genotype but also holds promise to transform treatment paradigms for the management of chronic infections and by interference with bacterial stress responses will promote the effectiveness of antimicrobials in clinical use to eradicate biofilm infections.
Max ERC Funding
1 998 750 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym Connections
Project Oligopoly Markets and Networks
Researcher (PI) Andrea Galeotti
Host Institution (HI) LONDON BUSINESS SCHOOL
Call Details Consolidator Grant (CoG), SH1, ERC-2016-COG
Summary Via our connections we learn about new ideas, quality of products, new investment opportunities and job opportunities. We influence and are influenced by our circle of friends. Firms are interconnected in complex processes of production and distribution. A firm’s decisions in a supply chain depends on other firms’ choices in the same supply chain, as well as on firms' behaviour in competing chains. Research on networks in the last 20 years has provided a series of tolls to study a system of interconnected economic agents. This project will advance the state of the art by further developing new applications of networks to better understand modern oligopoly markets.
The project is organised into two sub-projects. In sub-project 1 networks will be used to model diffusion and adoption of network goods. Different consumers' network locations will summarise different consumers' level of influence. The objectives are to understand how firms incorporate information about consumers' influence in their marketing strategies—pricing strategy and product design. It will provide a rigorous framework to evaluate how the increasing ability of firms to gather information on consumers’ influence affects outcomes of markets with network effects. In sub-project 2 networks will be used to model how inputs—e.g., intermediary goods and patents—are combined to deliver final goods. Possible applications are supply chains, communication networks and networks of patents. The objectives are to study firms' strategic behaviour, like pricing and R&D investments, in a complex process of production and distribution, and to understand the basic network metrics that are useful to describe market power. This is particularly important to provide a guide to competition authorities and alike when they evaluate mergers in complex interconnected markets.
Summary
Via our connections we learn about new ideas, quality of products, new investment opportunities and job opportunities. We influence and are influenced by our circle of friends. Firms are interconnected in complex processes of production and distribution. A firm’s decisions in a supply chain depends on other firms’ choices in the same supply chain, as well as on firms' behaviour in competing chains. Research on networks in the last 20 years has provided a series of tolls to study a system of interconnected economic agents. This project will advance the state of the art by further developing new applications of networks to better understand modern oligopoly markets.
The project is organised into two sub-projects. In sub-project 1 networks will be used to model diffusion and adoption of network goods. Different consumers' network locations will summarise different consumers' level of influence. The objectives are to understand how firms incorporate information about consumers' influence in their marketing strategies—pricing strategy and product design. It will provide a rigorous framework to evaluate how the increasing ability of firms to gather information on consumers’ influence affects outcomes of markets with network effects. In sub-project 2 networks will be used to model how inputs—e.g., intermediary goods and patents—are combined to deliver final goods. Possible applications are supply chains, communication networks and networks of patents. The objectives are to study firms' strategic behaviour, like pricing and R&D investments, in a complex process of production and distribution, and to understand the basic network metrics that are useful to describe market power. This is particularly important to provide a guide to competition authorities and alike when they evaluate mergers in complex interconnected markets.
Max ERC Funding
829 000 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym CRYOMATH
Project Cryo-electron microscopy: mathematical foundations and algorithms
Researcher (PI) Yoel SHKOLNISKY
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Consolidator Grant (CoG), PE1, ERC-2016-COG
Summary The importance of understanding the functions of the basic building blocks of life, such as proteins, cannot be overstated (as asserted by two recent Nobel prizes in Chemistry), as this understanding unravels the mechanisms that control all organisms. The critical step towards such an understanding is to reveal the structures of these building blocks. A leading method for resolving such structures is cryo-electron microscopy (cryo-EM), in which the structure of a molecule is recovered from its images taken by an electron microscope, by using sophisticated mathematical algorithms (to which my group has made several key mathematical and algorithmic contributions). Due to hardware breakthroughs in the past three years, cryo-EM has made a giant leap forward, introducing capabilities that until recently were unimaginable, opening an opportunity to revolutionize our biological understanding. As extracting information from cryo-EM experiments completely relies on mathematical algorithms, the method’s deep mathematical challenges that have emerged must be solved as soon as possible. Only then cryo-EM could realize its nearly inconceivable potential. These challenges, for which no adequate solutions exist (or none at all), focus on integrating information from huge sets of extremely noisy images reliability and efficiently. Based on the experience of my research group in developing algorithms for cryo-EM data processing, gained during the past eight years, we will address the three key open challenges of the field – a) deriving reliable and robust reconstruction algorithms from cryo-EM data, b) developing tools to process heterogeneous cryo-EM data sets, and c) devising validation and quality measures for structures determined from cryo-EM data. The fourth goal of the project, which ties all goals together and promotes the broad interdisciplinary impact of the project, is to merge all our algorithms into a software platform for state-of-the-art processing of cryo-EM data.
Summary
The importance of understanding the functions of the basic building blocks of life, such as proteins, cannot be overstated (as asserted by two recent Nobel prizes in Chemistry), as this understanding unravels the mechanisms that control all organisms. The critical step towards such an understanding is to reveal the structures of these building blocks. A leading method for resolving such structures is cryo-electron microscopy (cryo-EM), in which the structure of a molecule is recovered from its images taken by an electron microscope, by using sophisticated mathematical algorithms (to which my group has made several key mathematical and algorithmic contributions). Due to hardware breakthroughs in the past three years, cryo-EM has made a giant leap forward, introducing capabilities that until recently were unimaginable, opening an opportunity to revolutionize our biological understanding. As extracting information from cryo-EM experiments completely relies on mathematical algorithms, the method’s deep mathematical challenges that have emerged must be solved as soon as possible. Only then cryo-EM could realize its nearly inconceivable potential. These challenges, for which no adequate solutions exist (or none at all), focus on integrating information from huge sets of extremely noisy images reliability and efficiently. Based on the experience of my research group in developing algorithms for cryo-EM data processing, gained during the past eight years, we will address the three key open challenges of the field – a) deriving reliable and robust reconstruction algorithms from cryo-EM data, b) developing tools to process heterogeneous cryo-EM data sets, and c) devising validation and quality measures for structures determined from cryo-EM data. The fourth goal of the project, which ties all goals together and promotes the broad interdisciplinary impact of the project, is to merge all our algorithms into a software platform for state-of-the-art processing of cryo-EM data.
Max ERC Funding
1 751 250 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
