Project acronym AXONGROWTH
Project Systematic analysis of the molecular mechanisms underlying axon growth during development and following injury
Researcher (PI) Oren Schuldiner
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Consolidator Grant (CoG), LS5, ERC-2013-CoG
Summary Axon growth potential declines during development, contributing to the lack of effective regeneration in the adult central nervous system. What determines the intrinsic growth potential of neurites, and how such growth is regulated during development, disease and following injury is a fundamental question in neuroscience. Although multiple lines of evidence indicate that intrinsic growth capability is genetically encoded, its nature remains poorly defined. Neuronal remodeling of the Drosophila mushroom body offers a unique opportunity to study the mechanisms of various types of axon degeneration and growth. We have recently demonstrated that regrowth of axons following developmental pruning is not only distinct from initial outgrowth but also shares molecular similarities with regeneration following injury. In this proposal we combine state of the art tools from genomics, functional genetics and microscopy to perform a comprehensive study of the mechanisms underlying axon growth during development and following injury. First, we will combine genetic, biochemical and genomic studies to gain a mechanistic understanding of the developmental regrowth program. Next, we will perform extensive transcriptomic analyses and comparisons aimed at defining the genetic programs involved in initial axon growth, developmental regrowth, and regeneration following injury. Finally, we will harness the genetic power of Drosophila to perform a comprehensive functional analysis of genes and pathways, those previously known and new ones that we will discover, in various neurite growth paradigms. Importantly, these functional assays will be performed in the same organism, allowing us to use identical genetic mutations across our analyses. To this end, our identification of a new genetic program regulating developmental axon regrowth, together with emerging tools in genomics, places us in a unique position to gain a broad understanding of axon growth during development and following injury.
Summary
Axon growth potential declines during development, contributing to the lack of effective regeneration in the adult central nervous system. What determines the intrinsic growth potential of neurites, and how such growth is regulated during development, disease and following injury is a fundamental question in neuroscience. Although multiple lines of evidence indicate that intrinsic growth capability is genetically encoded, its nature remains poorly defined. Neuronal remodeling of the Drosophila mushroom body offers a unique opportunity to study the mechanisms of various types of axon degeneration and growth. We have recently demonstrated that regrowth of axons following developmental pruning is not only distinct from initial outgrowth but also shares molecular similarities with regeneration following injury. In this proposal we combine state of the art tools from genomics, functional genetics and microscopy to perform a comprehensive study of the mechanisms underlying axon growth during development and following injury. First, we will combine genetic, biochemical and genomic studies to gain a mechanistic understanding of the developmental regrowth program. Next, we will perform extensive transcriptomic analyses and comparisons aimed at defining the genetic programs involved in initial axon growth, developmental regrowth, and regeneration following injury. Finally, we will harness the genetic power of Drosophila to perform a comprehensive functional analysis of genes and pathways, those previously known and new ones that we will discover, in various neurite growth paradigms. Importantly, these functional assays will be performed in the same organism, allowing us to use identical genetic mutations across our analyses. To this end, our identification of a new genetic program regulating developmental axon regrowth, together with emerging tools in genomics, places us in a unique position to gain a broad understanding of axon growth during development and following injury.
Max ERC Funding
2 000 000 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym AZIDRUGS
Project Molecular tattooing: azidated compounds pave the path towards light-activated covalent inhibitors for drug development
Researcher (PI) András MÁLNÁSI-CSIZMADIA
Host Institution (HI) DRUGMOTIF KORLATOLT FELELOSSEGU TARSASAG
Call Details Proof of Concept (PoC), PC1, ERC-2013-PoC
Summary Until now the greatest limitation in the application of bioactive compounds has been the inability of confining them specifically to single cells or subcellular components within the organism. Our recently synthesized photoactive forms of bioactive compounds solve this problem. We have developed effective chemical synthesis methods to attach an azide group to small drug-like molecules, which makes them photoactive. As a result, light irradiation can induce the covalent attachment of these molecules to their target enzymes. By controlling the timing and position of light irradiation it is possible to confine the effect of these molecules in time and space. It is important to emphasize that azidation is the smallest possible modification (adding 3 nitrogen atoms) that makes a compound photoactive and based on our experience it does not alter biological activities of most of the original compounds.
Azidated inhibitors give unprecedented freedom to researchers because the covalent compound-target formations allow them to address questions which could not have been addressed before. Three major advantages are obtained by using azidated compounds 1: determination of small molecule interactome becomes highly effective, especially, the weak interactions can be determined, which was not possible before 2: it improves the pharmacodynamic and pharmacokinetic properties of biological compounds as the covalent attachment prolongs their effect. 3: Recently, we showed that photoactivation can be initiated by two-photon excitation, thereby confining the effect to femtoliter volumes and well-controlled spatial locations. This feature provides unprecedented spatial and temporal control in localizing the effect of biological compounds in cellular and subcelluler level in in vivo experiments. By realizing the need for photoactive compounds, the PI has established Drugmotif Ltd., a spin-off company, which provides the customers with special azidated chemicals for high-tech research.
Summary
Until now the greatest limitation in the application of bioactive compounds has been the inability of confining them specifically to single cells or subcellular components within the organism. Our recently synthesized photoactive forms of bioactive compounds solve this problem. We have developed effective chemical synthesis methods to attach an azide group to small drug-like molecules, which makes them photoactive. As a result, light irradiation can induce the covalent attachment of these molecules to their target enzymes. By controlling the timing and position of light irradiation it is possible to confine the effect of these molecules in time and space. It is important to emphasize that azidation is the smallest possible modification (adding 3 nitrogen atoms) that makes a compound photoactive and based on our experience it does not alter biological activities of most of the original compounds.
Azidated inhibitors give unprecedented freedom to researchers because the covalent compound-target formations allow them to address questions which could not have been addressed before. Three major advantages are obtained by using azidated compounds 1: determination of small molecule interactome becomes highly effective, especially, the weak interactions can be determined, which was not possible before 2: it improves the pharmacodynamic and pharmacokinetic properties of biological compounds as the covalent attachment prolongs their effect. 3: Recently, we showed that photoactivation can be initiated by two-photon excitation, thereby confining the effect to femtoliter volumes and well-controlled spatial locations. This feature provides unprecedented spatial and temporal control in localizing the effect of biological compounds in cellular and subcelluler level in in vivo experiments. By realizing the need for photoactive compounds, the PI has established Drugmotif Ltd., a spin-off company, which provides the customers with special azidated chemicals for high-tech research.
Max ERC Funding
150 000 €
Duration
Start date: 2013-12-01, End date: 2014-11-30
Project acronym B Massive
Project Binary massive black hole astrophysics
Researcher (PI) Alberto SESANA
Host Institution (HI) UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Call Details Consolidator Grant (CoG), PE9, ERC-2018-COG
Summary Massive black hole binaries (MBHBs) are the most extreme, fascinating yet elusive astrophysical objects in the Universe. Establishing observationally their existence will be a milestone for contemporary astronomy, providing a fundamental missing piece in the puzzle of galaxy formation, piercing through the (hydro)dynamical physical processes shaping dense galactic nuclei from parsec scales down to the event horizon, and probing gravity in extreme conditions.
We can both see and listen to MBHBs. Remarkably, besides arguably being among the brightest variable objects shining in the Cosmos, MBHBs are also the loudest gravitational wave (GW) sources in the Universe. As such, we shall take advantage of both the type of messengers – photons and gravitons – they are sending to us, which can now be probed by all-sky time-domain surveys and radio pulsar timing arrays (PTAs) respectively.
B MASSIVE leverages on a unique comprehensive approach combining theoretical astrophysics, radio and gravitational-wave astronomy and time-domain surveys, with state of the art data analysis techniques to: i) observationally prove the existence of MBHBs, ii) understand and constrain their astrophysics and dynamics, iii) enable and bring closer in time the direct detection of GWs with PTA.
As European PTA (EPTA) executive committee member and former I
International PTA (IPTA) chair, I am a driving force in the development of pulsar timing science world-wide, and the project will build on the profound knowledge, broad vision and wide collaboration network that established me as a world leader in the field of MBHB and GW astrophysics. B MASSIVE is extremely timely; a pulsar timing data set of unprecedented quality is being assembled by EPTA/IPTA, and Time-Domain astronomy surveys are at their dawn. In the long term, B MASSIVE will be a fundamental milestone establishing European leadership in the cutting-edge field of MBHB astrophysics in the era of LSST, SKA and LISA.
Summary
Massive black hole binaries (MBHBs) are the most extreme, fascinating yet elusive astrophysical objects in the Universe. Establishing observationally their existence will be a milestone for contemporary astronomy, providing a fundamental missing piece in the puzzle of galaxy formation, piercing through the (hydro)dynamical physical processes shaping dense galactic nuclei from parsec scales down to the event horizon, and probing gravity in extreme conditions.
We can both see and listen to MBHBs. Remarkably, besides arguably being among the brightest variable objects shining in the Cosmos, MBHBs are also the loudest gravitational wave (GW) sources in the Universe. As such, we shall take advantage of both the type of messengers – photons and gravitons – they are sending to us, which can now be probed by all-sky time-domain surveys and radio pulsar timing arrays (PTAs) respectively.
B MASSIVE leverages on a unique comprehensive approach combining theoretical astrophysics, radio and gravitational-wave astronomy and time-domain surveys, with state of the art data analysis techniques to: i) observationally prove the existence of MBHBs, ii) understand and constrain their astrophysics and dynamics, iii) enable and bring closer in time the direct detection of GWs with PTA.
As European PTA (EPTA) executive committee member and former I
International PTA (IPTA) chair, I am a driving force in the development of pulsar timing science world-wide, and the project will build on the profound knowledge, broad vision and wide collaboration network that established me as a world leader in the field of MBHB and GW astrophysics. B MASSIVE is extremely timely; a pulsar timing data set of unprecedented quality is being assembled by EPTA/IPTA, and Time-Domain astronomy surveys are at their dawn. In the long term, B MASSIVE will be a fundamental milestone establishing European leadership in the cutting-edge field of MBHB astrophysics in the era of LSST, SKA and LISA.
Max ERC Funding
1 532 750 €
Duration
Start date: 2019-09-01, End date: 2024-08-31
Project acronym BABE
Project Bodies across borders: oral and visual memory in Europe and beyond
Researcher (PI) Luisella Passerini
Host Institution (HI) EUROPEAN UNIVERSITY INSTITUTE
Call Details Advanced Grant (AdG), SH6, ERC-2011-ADG_20110406
Summary This project intends to study intercultural connections in contemporary Europe, engaging both native and ‘new’ Europeans. These connections are woven through the faculties of embodied subjects – memory, visuality and mobility – and concern the movement of people, ideas and images across the borders of European nation-states. These faculties are connected with that of affect, an increasingly important concept in history and the social sciences. Memory will be understood not only as oral or direct memory, but also as cultural memory, embodied in various cultural products. Our study aims to understand new forms of European identity, as these develop in an increasingly diasporic world. Europe today is not only a key site of immigration, after having been for centuries an area of emigration, but also a crucial point of arrival in a global network designed by mobile human beings.
Three parts will make up the project. The first will engage with bodies, their gendered dimension, performative capacities and connection to place. It will explore the ways certain bodies are ‘emplaced’ as ‘European’, while others are marked as alien, and contrast these discourses with the counter-narratives by visual artists. The second part will extend further the reflection on the role of the visual arts in challenging an emergent ‘Fortress Europe’ but also in re-imagining the memory of European colonialism. The work of some key artists will be shown to students in Italy and the Netherlands, both recent migrants and ‘natives’, creating an ‘induced reception’. The final part of the project will look at alternative imaginations of Europe, investigating the oral memories and ‘mental maps’ created by two migrant communities in Europe: from Peru and from the Horn of Africa.
Examining the heterogeneous micro-productions of mobility – whether ‘real’ or imagined/envisioned – will thus yield important lessons for the historical understanding of inclusion and exclusion in today’s Europe.
Summary
This project intends to study intercultural connections in contemporary Europe, engaging both native and ‘new’ Europeans. These connections are woven through the faculties of embodied subjects – memory, visuality and mobility – and concern the movement of people, ideas and images across the borders of European nation-states. These faculties are connected with that of affect, an increasingly important concept in history and the social sciences. Memory will be understood not only as oral or direct memory, but also as cultural memory, embodied in various cultural products. Our study aims to understand new forms of European identity, as these develop in an increasingly diasporic world. Europe today is not only a key site of immigration, after having been for centuries an area of emigration, but also a crucial point of arrival in a global network designed by mobile human beings.
Three parts will make up the project. The first will engage with bodies, their gendered dimension, performative capacities and connection to place. It will explore the ways certain bodies are ‘emplaced’ as ‘European’, while others are marked as alien, and contrast these discourses with the counter-narratives by visual artists. The second part will extend further the reflection on the role of the visual arts in challenging an emergent ‘Fortress Europe’ but also in re-imagining the memory of European colonialism. The work of some key artists will be shown to students in Italy and the Netherlands, both recent migrants and ‘natives’, creating an ‘induced reception’. The final part of the project will look at alternative imaginations of Europe, investigating the oral memories and ‘mental maps’ created by two migrant communities in Europe: from Peru and from the Horn of Africa.
Examining the heterogeneous micro-productions of mobility – whether ‘real’ or imagined/envisioned – will thus yield important lessons for the historical understanding of inclusion and exclusion in today’s Europe.
Max ERC Funding
1 488 501 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym BACKUP
Project Unveiling the relationship between brain connectivity and function by integrated photonics
Researcher (PI) Lorenzo PAVESI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI TRENTO
Call Details Advanced Grant (AdG), PE7, ERC-2017-ADG
Summary I will address the fundamental question of which is the role of neuron activity and plasticity in information elaboration and storage in the brain. I, together with an interdisciplinary team, will develop a hybrid neuro-morphic computing platform. Integrated photonic circuits will be interfaced to both electronic circuits and neuronal circuits (in vitro experiments) to emulate brain functions and develop schemes able to supplement (backup) neuronal functions. The photonic network is based on massive reconfigurable matrices of nonlinear nodes formed by microring resonators, which enter in regime of self-pulsing and chaos by positive optical feedback. These networks resemble human brain. I will push this analogy further by interfacing the photonic network with neurons making hybrid network. By using optogenetics, I will control the synaptic strengthen-ing and the neuron activity. Deep learning algorithms will model the biological network functionality, initial-ly within a separate artificial network and, then, in an integrated hybrid artificial-biological network.
My project aims at:
1. Developing a photonic integrated reservoir-computing network (RCN);
2. Developing dynamic memories in photonic integrated circuits using RCN;
3. Developing hybrid interfaces between a neuronal network and a photonic integrated circuit;
4. Developing a hybrid electronic, photonic and biological network that computes jointly;
5. Addressing neuronal network activity by photonic RCN to simulate in vitro memory storage and retrieval;
6. Elaborating the signal from RCN and neuronal circuits in order to cope with plastic changes in pathologi-cal brain conditions such as amnesia and epilepsy.
The long-term vision is that hybrid neuromorphic photonic networks will (a) clarify the way brain thinks, (b) compute beyond von Neumann, and (c) control and supplement specific neuronal functions.
Summary
I will address the fundamental question of which is the role of neuron activity and plasticity in information elaboration and storage in the brain. I, together with an interdisciplinary team, will develop a hybrid neuro-morphic computing platform. Integrated photonic circuits will be interfaced to both electronic circuits and neuronal circuits (in vitro experiments) to emulate brain functions and develop schemes able to supplement (backup) neuronal functions. The photonic network is based on massive reconfigurable matrices of nonlinear nodes formed by microring resonators, which enter in regime of self-pulsing and chaos by positive optical feedback. These networks resemble human brain. I will push this analogy further by interfacing the photonic network with neurons making hybrid network. By using optogenetics, I will control the synaptic strengthen-ing and the neuron activity. Deep learning algorithms will model the biological network functionality, initial-ly within a separate artificial network and, then, in an integrated hybrid artificial-biological network.
My project aims at:
1. Developing a photonic integrated reservoir-computing network (RCN);
2. Developing dynamic memories in photonic integrated circuits using RCN;
3. Developing hybrid interfaces between a neuronal network and a photonic integrated circuit;
4. Developing a hybrid electronic, photonic and biological network that computes jointly;
5. Addressing neuronal network activity by photonic RCN to simulate in vitro memory storage and retrieval;
6. Elaborating the signal from RCN and neuronal circuits in order to cope with plastic changes in pathologi-cal brain conditions such as amnesia and epilepsy.
The long-term vision is that hybrid neuromorphic photonic networks will (a) clarify the way brain thinks, (b) compute beyond von Neumann, and (c) control and supplement specific neuronal functions.
Max ERC Funding
2 499 825 €
Duration
Start date: 2018-11-01, End date: 2023-10-31
Project acronym BACNK
Project Recognition of bacteria by NK cells
Researcher (PI) Ofer Mandelboim
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Advanced Grant (AdG), LS6, ERC-2012-ADG_20120314
Summary NK cells that are well known by their ability to recognize and eliminate virus infected and tumor cells were also implicated in the defence against bacteria. However, the recognition of bacteria by NK cells is only poorly understood. we do not know how bacteria are recognized and the functional consequences of such recognition are also weakly understood. In the current proposal we aimed at determining the “NK cell receptor-bacterial interactome”. We will examine the hypothesis that NK inhibitory and activating receptors are directly involved in bacterial recognition. This ground breaking hypothesis is based on our preliminary results in which we show that several NK cell receptors directly recognize various bacterial strains as well as on a few other publications. We will generate various mice knockouts for NCR1 (a major NK killer receptor) and determine their microbiota to understand the physiological function of NCR1 and whether certain bacterial strains affects its activity. We will use different human and mouse NK killer and inhibitory receptors fused to IgG1 to pull-down bacteria from saliva and fecal samples and then use 16S rRNA analysis and next generation sequencing to determine the nature of the bacteria species isolated. We will identify the bacterial ligands that are recognized by the relevant NK cell receptors, using bacterial random transposon insertion mutagenesis approach. We will end this research with functional assays. In the wake of the emerging threat of bacterial drug resistance and the involvement of bacteria in the pathogenesis of many different chronic diseases and in shaping the immune response, the completion of this study will open a new field of research; the direct recognition of bacteria by NK cell receptors.
Summary
NK cells that are well known by their ability to recognize and eliminate virus infected and tumor cells were also implicated in the defence against bacteria. However, the recognition of bacteria by NK cells is only poorly understood. we do not know how bacteria are recognized and the functional consequences of such recognition are also weakly understood. In the current proposal we aimed at determining the “NK cell receptor-bacterial interactome”. We will examine the hypothesis that NK inhibitory and activating receptors are directly involved in bacterial recognition. This ground breaking hypothesis is based on our preliminary results in which we show that several NK cell receptors directly recognize various bacterial strains as well as on a few other publications. We will generate various mice knockouts for NCR1 (a major NK killer receptor) and determine their microbiota to understand the physiological function of NCR1 and whether certain bacterial strains affects its activity. We will use different human and mouse NK killer and inhibitory receptors fused to IgG1 to pull-down bacteria from saliva and fecal samples and then use 16S rRNA analysis and next generation sequencing to determine the nature of the bacteria species isolated. We will identify the bacterial ligands that are recognized by the relevant NK cell receptors, using bacterial random transposon insertion mutagenesis approach. We will end this research with functional assays. In the wake of the emerging threat of bacterial drug resistance and the involvement of bacteria in the pathogenesis of many different chronic diseases and in shaping the immune response, the completion of this study will open a new field of research; the direct recognition of bacteria by NK cell receptors.
Max ERC Funding
2 499 800 €
Duration
Start date: 2013-03-01, End date: 2018-02-28
Project acronym BACTERIAL RESPONSE
Project New Concepts in Bacterial Response to their Surroundings
Researcher (PI) Sigal Ben-Yehuda
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Advanced Grant (AdG), LS6, ERC-2013-ADG
Summary Bacteria in nature exhibit remarkable capacity to sense their surroundings and rapidly adapt to diverse conditions by gaining new beneficial traits. This extraordinary feature facilitates their survival when facing extreme environments. Utilizing Bacillus subtilis as our primary model organism, we propose to study two facets of this vital bacterial attribute: communication via extracellular nanotubes, and persistence as resilient spores while maintaining the potential to revive. Exploring these fascinating aspects of bacterial physiology is likely to change our view as to how bacteria sense, respond, endure and communicate with their extracellular environment.
We have recently discovered a previously uncharacterized mode of bacterial communication, mediated by tubular extensions (nanotubes) that bridge neighboring cells, providing a route for exchange of intracellular molecules. Nanotube-mediated molecular sharing may represent a key form of bacterial communication in nature, allowing for the emergence of new phenotypes and increasing survival in fluctuating environments. Here we propose to develop strategies for observing nanotube formation and molecular exchange in living bacterial cells, and to characterize the molecular composition of nanotubes. We will explore the premise that nanotubes serve as a strategy to expand the cell surface, and will determine whether nanotubes provide a conduit for phage infection and spreading. Furthermore, the formation and functionality of interspecies nanotubes will be explored. An additional mode employed by bacteria to achieve extreme robustness is the ability to reside as long lasting spores. Previously held views considered the spore to be dormant and metabolically inert. However, we have recently shown that at least one week following spore formation, during an adaptive period, the spore senses and responds to environmental cues and undergoes corresponding molecular changes, influencing subsequent emergence from quiescence.
Summary
Bacteria in nature exhibit remarkable capacity to sense their surroundings and rapidly adapt to diverse conditions by gaining new beneficial traits. This extraordinary feature facilitates their survival when facing extreme environments. Utilizing Bacillus subtilis as our primary model organism, we propose to study two facets of this vital bacterial attribute: communication via extracellular nanotubes, and persistence as resilient spores while maintaining the potential to revive. Exploring these fascinating aspects of bacterial physiology is likely to change our view as to how bacteria sense, respond, endure and communicate with their extracellular environment.
We have recently discovered a previously uncharacterized mode of bacterial communication, mediated by tubular extensions (nanotubes) that bridge neighboring cells, providing a route for exchange of intracellular molecules. Nanotube-mediated molecular sharing may represent a key form of bacterial communication in nature, allowing for the emergence of new phenotypes and increasing survival in fluctuating environments. Here we propose to develop strategies for observing nanotube formation and molecular exchange in living bacterial cells, and to characterize the molecular composition of nanotubes. We will explore the premise that nanotubes serve as a strategy to expand the cell surface, and will determine whether nanotubes provide a conduit for phage infection and spreading. Furthermore, the formation and functionality of interspecies nanotubes will be explored. An additional mode employed by bacteria to achieve extreme robustness is the ability to reside as long lasting spores. Previously held views considered the spore to be dormant and metabolically inert. However, we have recently shown that at least one week following spore formation, during an adaptive period, the spore senses and responds to environmental cues and undergoes corresponding molecular changes, influencing subsequent emergence from quiescence.
Max ERC Funding
1 497 800 €
Duration
Start date: 2014-04-01, End date: 2019-03-31
Project acronym BACTERIAL SPORES
Project Investigating the Nature of Bacterial Spores
Researcher (PI) Sigal Ben-Yehuda
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Starting Grant (StG), LS3, ERC-2007-StG
Summary When triggered by nutrient limitation, the Gram-positive bacterium Bacillus subtilis and its relatives enter a pathway of cellular differentiation culminating in the formation of a dormant cell type called a spore, the most resilient cell type known. Bacterial spores can survive for long periods of time and are able to endure extremes of heat, radiation and chemical assault. Remarkably, dormant spores can rapidly convert back to actively growing cells by a process called germination. Consequently, spore forming bacteria, including dangerous pathogens, (such as C. botulinum and B. anthracis) are highly resistant to antibacterial treatments and difficult to eradicate. Despite significant advances in our understanding of the process of spore formation, little is known about the nature of the mature spore. It is unrevealed how dormancy is maintained within the spore and how it is ceased, as the organization and the dynamics of the spore macromolecules remain obscure. The unusual biochemical and biophysical characteristics of the dormant spore make it a challenging biological system to investigate using conventional methods, and thus set the need to develop innovative approaches to study spore biology. We propose to explore the nature of spores by using B. subtilis as a primary experimental system. We intend to: (1) define the architecture of the spore chromosome, (2) track the complexity and fate of mRNA and protein molecules during sporulation, dormancy and germination, (3) revisit the basic notion of the spore dormancy (is it metabolically inert?), (4) compare the characteristics of bacilli spores from diverse ecophysiological groups, (5) investigate the features of spores belonging to distant bacterial genera, (6) generate an integrative database that categorizes the molecular features of spores. Our study will provide original insights and introduce novel concepts to the field of spore biology and may help devise innovative ways to combat spore forming pathogens.
Summary
When triggered by nutrient limitation, the Gram-positive bacterium Bacillus subtilis and its relatives enter a pathway of cellular differentiation culminating in the formation of a dormant cell type called a spore, the most resilient cell type known. Bacterial spores can survive for long periods of time and are able to endure extremes of heat, radiation and chemical assault. Remarkably, dormant spores can rapidly convert back to actively growing cells by a process called germination. Consequently, spore forming bacteria, including dangerous pathogens, (such as C. botulinum and B. anthracis) are highly resistant to antibacterial treatments and difficult to eradicate. Despite significant advances in our understanding of the process of spore formation, little is known about the nature of the mature spore. It is unrevealed how dormancy is maintained within the spore and how it is ceased, as the organization and the dynamics of the spore macromolecules remain obscure. The unusual biochemical and biophysical characteristics of the dormant spore make it a challenging biological system to investigate using conventional methods, and thus set the need to develop innovative approaches to study spore biology. We propose to explore the nature of spores by using B. subtilis as a primary experimental system. We intend to: (1) define the architecture of the spore chromosome, (2) track the complexity and fate of mRNA and protein molecules during sporulation, dormancy and germination, (3) revisit the basic notion of the spore dormancy (is it metabolically inert?), (4) compare the characteristics of bacilli spores from diverse ecophysiological groups, (5) investigate the features of spores belonging to distant bacterial genera, (6) generate an integrative database that categorizes the molecular features of spores. Our study will provide original insights and introduce novel concepts to the field of spore biology and may help devise innovative ways to combat spore forming pathogens.
Max ERC Funding
1 630 000 €
Duration
Start date: 2008-10-01, End date: 2013-09-30
Project acronym BacterialCORE
Project Widespread Bacterial CORE Complex Executes Intra- and Inter-Kingdom Cytoplasmic Molecular Trade
Researcher (PI) Sigal BEN-YEHUDA
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Synergy Grants (SyG), SyG3LSa, ERC-2018-SyG
Summary The enormous versatility of bacteria enables the formation of multi-species communities that colonize nearly every niche on earth, making them the dominant life form and a major component of the biomass. Exchange of molecular information among neighboring bacteria in such communities, as well as between bacteria and proximal eukaryotic cells, is key for bacterial success. Yet, the principles controlling these multicellular interactions are poorly defined. Here we describe the identification of a bacterial protein complex, herein termed CORE, whose function is to traffic cytoplasmic molecules among different bacterial species, and between pathogenic bacteria and their human host cells. The CORE is composed of five membrane proteins, highly conserved across the entire bacterial kingdom, providing a ubiquitous platform that facilitates both intra- and inter-kingdom crosstalk. Our preliminary data support the idea that the CORE acts as a shared module for the assembly of larger apparatuses, executing this universal molecular flow among organisms. We propose to elucidate components, structure and biogenesis of the CORE machinery, operating during bacteria-bacteria and pathogen-host interactions. We further aim to provide an unbiased-global view of the extent and identity of cytoplasmic molecules traded via CORE including metabolites, proteins and RNA, and to reveal the criteria determining the specificity of the transported cargo. Furthermore, we intend to decipher the impact of CORE-mediated molecular exchange on bacterial physiology and virulence, and devise anti-CORE compounds to combat pathogenic bacteria. This study is expected to transform the way we currently view bacterial communities and host-pathogen interactions. We anticipate these findings to lead to the development of creative strategies to modulate, predict and even design bacterial communities, and lay the foundation for new and innovative approaches to fight bacterial diseases.
Summary
The enormous versatility of bacteria enables the formation of multi-species communities that colonize nearly every niche on earth, making them the dominant life form and a major component of the biomass. Exchange of molecular information among neighboring bacteria in such communities, as well as between bacteria and proximal eukaryotic cells, is key for bacterial success. Yet, the principles controlling these multicellular interactions are poorly defined. Here we describe the identification of a bacterial protein complex, herein termed CORE, whose function is to traffic cytoplasmic molecules among different bacterial species, and between pathogenic bacteria and their human host cells. The CORE is composed of five membrane proteins, highly conserved across the entire bacterial kingdom, providing a ubiquitous platform that facilitates both intra- and inter-kingdom crosstalk. Our preliminary data support the idea that the CORE acts as a shared module for the assembly of larger apparatuses, executing this universal molecular flow among organisms. We propose to elucidate components, structure and biogenesis of the CORE machinery, operating during bacteria-bacteria and pathogen-host interactions. We further aim to provide an unbiased-global view of the extent and identity of cytoplasmic molecules traded via CORE including metabolites, proteins and RNA, and to reveal the criteria determining the specificity of the transported cargo. Furthermore, we intend to decipher the impact of CORE-mediated molecular exchange on bacterial physiology and virulence, and devise anti-CORE compounds to combat pathogenic bacteria. This study is expected to transform the way we currently view bacterial communities and host-pathogen interactions. We anticipate these findings to lead to the development of creative strategies to modulate, predict and even design bacterial communities, and lay the foundation for new and innovative approaches to fight bacterial diseases.
Max ERC Funding
6 930 796 €
Duration
Start date: 2019-04-01, End date: 2025-03-31
Project acronym BANDWIDTH
Project The cost of limited communication bandwidth in distributed computing
Researcher (PI) Keren CENSOR-HILLEL
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), PE6, ERC-2017-STG
Summary Distributed systems underlie many modern technologies, a prime example being the Internet. The ever-increasing abundance of distributed systems necessitates their design and usage to be backed by strong theoretical foundations.
A major challenge that distributed systems face is the lack of a central authority, which brings many aspects of uncertainty into the environment, in the form of unknown network topology or unpredictable dynamic behavior. A practical restriction of distributed systems, which is at the heart of this proposal, is the limited bandwidth available for communication between the network components.
A central family of distributed tasks is that of local tasks, which are informally described as tasks which are possible to solve by sending information through only a relatively small number of hops. A cornerstone example is the need to break symmetry and provide a better utilization of resources, which can be obtained by the task of producing a valid coloring of the nodes given some small number of colors. Amazingly, there are still huge gaps between the known upper and lower bounds for the complexity of many local tasks. This holds even if one allows powerful assumptions of unlimited bandwidth. While some known algorithms indeed use small messages, the complexity gaps are even larger compared to the unlimited bandwidth case. This is not a mere coincidence, and in fact the existing theoretical infrastructure is provably incapable of
giving stronger lower bounds for many local tasks under limited bandwidth.
This proposal zooms in on this crucial blind spot in the current literature on the theory of distributed computing, namely, the study of local tasks under limited bandwidth. The goal of this research is to produce fast algorithms for fundamental distributed local tasks under restricted bandwidth, as well as understand their limitations by providing lower bounds.
Summary
Distributed systems underlie many modern technologies, a prime example being the Internet. The ever-increasing abundance of distributed systems necessitates their design and usage to be backed by strong theoretical foundations.
A major challenge that distributed systems face is the lack of a central authority, which brings many aspects of uncertainty into the environment, in the form of unknown network topology or unpredictable dynamic behavior. A practical restriction of distributed systems, which is at the heart of this proposal, is the limited bandwidth available for communication between the network components.
A central family of distributed tasks is that of local tasks, which are informally described as tasks which are possible to solve by sending information through only a relatively small number of hops. A cornerstone example is the need to break symmetry and provide a better utilization of resources, which can be obtained by the task of producing a valid coloring of the nodes given some small number of colors. Amazingly, there are still huge gaps between the known upper and lower bounds for the complexity of many local tasks. This holds even if one allows powerful assumptions of unlimited bandwidth. While some known algorithms indeed use small messages, the complexity gaps are even larger compared to the unlimited bandwidth case. This is not a mere coincidence, and in fact the existing theoretical infrastructure is provably incapable of
giving stronger lower bounds for many local tasks under limited bandwidth.
This proposal zooms in on this crucial blind spot in the current literature on the theory of distributed computing, namely, the study of local tasks under limited bandwidth. The goal of this research is to produce fast algorithms for fundamental distributed local tasks under restricted bandwidth, as well as understand their limitations by providing lower bounds.
Max ERC Funding
1 486 480 €
Duration
Start date: 2018-06-01, End date: 2023-05-31
