Project acronym ARISE
Project The Ecology of Antibiotic Resistance
Researcher (PI) Roy Kishony
Host Institution (HI) TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Call Details Starting Grant (StG), LS8, ERC-2011-StG_20101109
Summary Main goal. We aim to understand the puzzling coexistence of antibiotic-resistant and antibiotic-sensitive species in natural soil environments, using novel quantitative experimental techniques and mathematical analysis. The ecological insights gained will be translated into novel treatment strategies for combating antibiotic resistance.
Background. Microbial soil ecosystems comprise communities of species interacting through copious secretion of antibiotics and other chemicals. Defence mechanisms, i.e. resistance to antibiotics, are ubiquitous in these wild communities. However, in sharp contrast to clinical settings, resistance does not take over the population. Our hypothesis is that the ecological setting provides natural mechanisms that keep antibiotic resistance in check. We are motivated by our recent finding that specific antibiotic combinations can generate selection against resistance and that soil microbial strains produce compounds that directly target antibiotic resistant mechanisms.
Approaches. We will: (1) Isolate natural bacterial species from individual grains of soil, characterize their ability to produce and resist antibiotics and identify the spatial scale for correlations between resistance and production. (2) Systematically measure interactions between species and identify interaction patterns enriched in co-existing communities derived from the same grain of soil. (3) Introducing fluorescently-labelled resistant and sensitive strains into natural soil, we will measure the fitness cost and benefit of antibiotic resistance in situ and identify natural compounds that select against resistance. (4) Test whether such “selection-inverting” compounds can slow evolution of resistance to antibiotics in continuous culture experiments.
Conclusions. These findings will provide insights into the ecological processes that keep antibiotic resistance in check, and will suggest novel antimicrobial treatment strategies.
Summary
Main goal. We aim to understand the puzzling coexistence of antibiotic-resistant and antibiotic-sensitive species in natural soil environments, using novel quantitative experimental techniques and mathematical analysis. The ecological insights gained will be translated into novel treatment strategies for combating antibiotic resistance.
Background. Microbial soil ecosystems comprise communities of species interacting through copious secretion of antibiotics and other chemicals. Defence mechanisms, i.e. resistance to antibiotics, are ubiquitous in these wild communities. However, in sharp contrast to clinical settings, resistance does not take over the population. Our hypothesis is that the ecological setting provides natural mechanisms that keep antibiotic resistance in check. We are motivated by our recent finding that specific antibiotic combinations can generate selection against resistance and that soil microbial strains produce compounds that directly target antibiotic resistant mechanisms.
Approaches. We will: (1) Isolate natural bacterial species from individual grains of soil, characterize their ability to produce and resist antibiotics and identify the spatial scale for correlations between resistance and production. (2) Systematically measure interactions between species and identify interaction patterns enriched in co-existing communities derived from the same grain of soil. (3) Introducing fluorescently-labelled resistant and sensitive strains into natural soil, we will measure the fitness cost and benefit of antibiotic resistance in situ and identify natural compounds that select against resistance. (4) Test whether such “selection-inverting” compounds can slow evolution of resistance to antibiotics in continuous culture experiments.
Conclusions. These findings will provide insights into the ecological processes that keep antibiotic resistance in check, and will suggest novel antimicrobial treatment strategies.
Max ERC Funding
1 900 000 €
Duration
Start date: 2012-09-01, End date: 2018-08-31
Project acronym BEAMING
Project Detecting massive-planet/brown-dwarf/low-mass-stellar companions with the beaming effect
Researcher (PI) Moshe Zvi Mazeh
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Advanced Grant (AdG), PE9, ERC-2011-ADG_20110209
Summary "I propose to lead an international observational effort to characterize the population of massive planets, brown dwarf and stellar secondaries orbiting their parent stars with short periods, up to 10-30 days. The effort will utilize the superb, accurate, continuous lightcurves of more than hundred thousand stars obtained recently by two space missions – CoRoT and Kepler. I propose to use these lightcurves to detect non-transiting low-mass companions with a new algorithm, BEER, which I developed recently together with Simchon Faigler. BEER searches for the beaming effect, which causes the stellar intensity to increase if the star is moving towards the observer. The combination of the beaming effect with other modulations induced by a low-mass companion produces periodic modulation with a specific signature, which is used to detect small non-transiting companions. The accuracy of the space mission lightcurves is enough to detect massive planets with short periods. The proposed project is equivalent to a radial-velocity survey of tens of thousands of stars, instead of the presently active surveys which observe only hundreds of stars.
We will use an assortment of telescopes to perform radial velocity follow-up observations in order to confirm the existence of the detected companions, and to derive their masses and orbital eccentricities. We will discover many tens, if not hundreds, of new massive planets and brown dwarfs with short periods, and many thousands of new binaries. The findings will enable us to map the mass, period, and eccentricity distributions of planets and stellar companions, determine the upper mass of planets, understand the nature of the brown-dwarf desert, and put strong constrains on the theory of planet and binary formation and evolution."
Summary
"I propose to lead an international observational effort to characterize the population of massive planets, brown dwarf and stellar secondaries orbiting their parent stars with short periods, up to 10-30 days. The effort will utilize the superb, accurate, continuous lightcurves of more than hundred thousand stars obtained recently by two space missions – CoRoT and Kepler. I propose to use these lightcurves to detect non-transiting low-mass companions with a new algorithm, BEER, which I developed recently together with Simchon Faigler. BEER searches for the beaming effect, which causes the stellar intensity to increase if the star is moving towards the observer. The combination of the beaming effect with other modulations induced by a low-mass companion produces periodic modulation with a specific signature, which is used to detect small non-transiting companions. The accuracy of the space mission lightcurves is enough to detect massive planets with short periods. The proposed project is equivalent to a radial-velocity survey of tens of thousands of stars, instead of the presently active surveys which observe only hundreds of stars.
We will use an assortment of telescopes to perform radial velocity follow-up observations in order to confirm the existence of the detected companions, and to derive their masses and orbital eccentricities. We will discover many tens, if not hundreds, of new massive planets and brown dwarfs with short periods, and many thousands of new binaries. The findings will enable us to map the mass, period, and eccentricity distributions of planets and stellar companions, determine the upper mass of planets, understand the nature of the brown-dwarf desert, and put strong constrains on the theory of planet and binary formation and evolution."
Max ERC Funding
1 737 600 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym CELLREPROGRAMMING
Project Uncovering the Mechanisms of Epigenetic Reprogramming of Pluripotent and Somatic Cell States
Researcher (PI) Yaqub Hanna
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Starting Grant (StG), LS3, ERC-2011-StG_20101109
Summary The generation of animals by nuclear transfer demonstrated that the epigenetic state of somatic cells could be reset to an embryonic state, capable of directing the development of a new organism. The nuclear cloning technology is of interest for transplantation medicine, but any application is hampered by the inefficiency and ethical problems. A breakthrough solving these issues has been the in vitro derivation of reprogrammed Induced Pluripotent Stem “iPS” cells by the ectopic expression of defined transcription factors in somatic cells. iPS cells recapitulate all defining features of embryo-derived pluripotent stem cells, including the ability to differentiate into all somatic cell types. Further, recent publications have demonstrated the ability to directly trans-differentiate somatic cell types by ectopic expression of lineage specification factors. Thus, it is becoming increasingly clear that an ultimate goal in the stem cell field is to enable scientists to have the power to safely manipulate somatic cells by “reprogramming” their behavior at will. However, to frame this challenge, we must understand the basic mechanisms underlying the generation of reprogrammed cells in parallel to designing strategies for their medical application and their use in human disease specific research. In this ERC Starting Grant proposal, I describe comprehensive lines of experimentation that I plan to conduct in my new lab scheduled to open in April 2011 at the Weizmann Institute of Science. We will utilize exacting transgenic mammalian models and high throughput sequencing and genomic screening tools for in depth characterization of the molecular “rules” of rewiring the epigenome of somatic and pluripotent cell states. The proposed research endeavors will not only contribute to the development of safer strategies for cell reprogramming, but will also help decipher how diverse gene expression programs lead to cellular specification during normal development.
Summary
The generation of animals by nuclear transfer demonstrated that the epigenetic state of somatic cells could be reset to an embryonic state, capable of directing the development of a new organism. The nuclear cloning technology is of interest for transplantation medicine, but any application is hampered by the inefficiency and ethical problems. A breakthrough solving these issues has been the in vitro derivation of reprogrammed Induced Pluripotent Stem “iPS” cells by the ectopic expression of defined transcription factors in somatic cells. iPS cells recapitulate all defining features of embryo-derived pluripotent stem cells, including the ability to differentiate into all somatic cell types. Further, recent publications have demonstrated the ability to directly trans-differentiate somatic cell types by ectopic expression of lineage specification factors. Thus, it is becoming increasingly clear that an ultimate goal in the stem cell field is to enable scientists to have the power to safely manipulate somatic cells by “reprogramming” their behavior at will. However, to frame this challenge, we must understand the basic mechanisms underlying the generation of reprogrammed cells in parallel to designing strategies for their medical application and their use in human disease specific research. In this ERC Starting Grant proposal, I describe comprehensive lines of experimentation that I plan to conduct in my new lab scheduled to open in April 2011 at the Weizmann Institute of Science. We will utilize exacting transgenic mammalian models and high throughput sequencing and genomic screening tools for in depth characterization of the molecular “rules” of rewiring the epigenome of somatic and pluripotent cell states. The proposed research endeavors will not only contribute to the development of safer strategies for cell reprogramming, but will also help decipher how diverse gene expression programs lead to cellular specification during normal development.
Max ERC Funding
1 960 000 €
Duration
Start date: 2011-11-01, End date: 2016-10-31
Project acronym GRB-SN
Project The Gamma Ray Burst – Supernova Connection
and Shock Breakout Physics
Researcher (PI) Ehud Nakar
Host Institution (HI) TEL AVIV UNIVERSITY
Call Details Starting Grant (StG), PE9, ERC-2011-StG_20101014
Summary Long gamma ray bursts (long GRBs) and core-collapse supernovae (CCSNe) are two of the most spectacular explosions in the Universe. They are a focal point of research for many reasons. Nevertheless, despite considerable effort during the last several decades, there are still many fundamental open questions regarding their physics.
Long GRBs and CCSNe are related. We know that they are both an outcome of a massive star collapse, where in some cases, such collapse produces simultaneously a GRB and a SN. However, we do not know how a single stellar collapse can produce these two apparently very different explosions. The GRB-SN connection raises many questions, but it also offers new opportunities to learn on the two types of explosions.
The focus of the proposed research is on the connection between CCSNe and GRBs, and on the physics of shock breakout. As I explain in this proposal, shock breakouts play an important role in this connection and therefore, I will develop a comprehensive theory of relativistic and Newtonian shock breakout. In addition, I will study the propagation of relativistic jets inside stars, including the effects of jet propagation and GRB engine on the emerging SN. This will be done by a set of interrelated projects that carefully combine analytic calculations and numerical simulations. Together, these projects will be the first to model a GRB and a SN that are simultaneously produced in a single star. This in turn will be used to gain new insights into long GRBs and CCSNe in general.
This research will also make a direct contribution to cosmic explosions research in general. Any observable cosmic explosion must go through a shock breakout and a considerable effort is invested these days in large field of view surveys in search for these breakouts. This program will provide a new theoretical base for the interpretation of the upcoming observations.
Summary
Long gamma ray bursts (long GRBs) and core-collapse supernovae (CCSNe) are two of the most spectacular explosions in the Universe. They are a focal point of research for many reasons. Nevertheless, despite considerable effort during the last several decades, there are still many fundamental open questions regarding their physics.
Long GRBs and CCSNe are related. We know that they are both an outcome of a massive star collapse, where in some cases, such collapse produces simultaneously a GRB and a SN. However, we do not know how a single stellar collapse can produce these two apparently very different explosions. The GRB-SN connection raises many questions, but it also offers new opportunities to learn on the two types of explosions.
The focus of the proposed research is on the connection between CCSNe and GRBs, and on the physics of shock breakout. As I explain in this proposal, shock breakouts play an important role in this connection and therefore, I will develop a comprehensive theory of relativistic and Newtonian shock breakout. In addition, I will study the propagation of relativistic jets inside stars, including the effects of jet propagation and GRB engine on the emerging SN. This will be done by a set of interrelated projects that carefully combine analytic calculations and numerical simulations. Together, these projects will be the first to model a GRB and a SN that are simultaneously produced in a single star. This in turn will be used to gain new insights into long GRBs and CCSNe in general.
This research will also make a direct contribution to cosmic explosions research in general. Any observable cosmic explosion must go through a shock breakout and a considerable effort is invested these days in large field of view surveys in search for these breakouts. This program will provide a new theoretical base for the interpretation of the upcoming observations.
Max ERC Funding
1 468 180 €
Duration
Start date: 2012-01-01, End date: 2017-12-31
Project acronym INFOTROPHIC
Project Algal Bloom Dynamics: From Cellular Mechanisms to Trophic Level Interactions
Researcher (PI) Assaf Vardi
Host Institution (HI) WEIZMANN INSTITUTE OF SCIENCE
Call Details Starting Grant (StG), LS8, ERC-2011-StG_20101109
Summary Marine phytoplankton are the basis of marine food webs and are responsible for nearly 50% of the global annual carbon-based primary production. Since phytoplankton exert such a global-scale influence on climate, we are interested in understanding what controls their cell fate during bloom “boom and bust” dynamics. Despite their importance, the molecular basis for their ecological success is still in its infancy. In recent years, the wealth of genomic information from marine microbes, coupled with molecular resources and analytical tools, provide an unprecedented opportunity to address fundamental questions about their unique evolutionary history and ecological role. Nevertheless, there is a critical need to “decode” the genomic resources and translate them into cellular mechanisms, community structure and, eventually, to their role in ecosystem function. This proposed research aims to provide novel insights into the role of a chemical-based “arms race” that mediates and structures the microbial interactions in the marine environment. We will dissect unexplored signaling pathways employed by phytoplankton during sensing and acclimation to changes in their environment. Our overarching objective is to unravel the role of infochemicals and related gene products in regulating phytoplankton surveillance systems in response to environmental stress conditions. We will focus on the three major biotic interactions of key dominant algal groups in the oceans; intercellular signaling in diatoms, host-virus interactions in coccolithophores and predator-prey interactions. We will provide a suite of cellular probes and metabolic biomarkers that will allow in situ detection of chemical signaling and biotic interactions in the oceans and will highlight their role in shaping microbial food webs. Our vision is to provide novel cellular concepts and molecular tools to the link between the intricate mechanisms of cell signaling and stress response, and large biogeochemical cycles.
Summary
Marine phytoplankton are the basis of marine food webs and are responsible for nearly 50% of the global annual carbon-based primary production. Since phytoplankton exert such a global-scale influence on climate, we are interested in understanding what controls their cell fate during bloom “boom and bust” dynamics. Despite their importance, the molecular basis for their ecological success is still in its infancy. In recent years, the wealth of genomic information from marine microbes, coupled with molecular resources and analytical tools, provide an unprecedented opportunity to address fundamental questions about their unique evolutionary history and ecological role. Nevertheless, there is a critical need to “decode” the genomic resources and translate them into cellular mechanisms, community structure and, eventually, to their role in ecosystem function. This proposed research aims to provide novel insights into the role of a chemical-based “arms race” that mediates and structures the microbial interactions in the marine environment. We will dissect unexplored signaling pathways employed by phytoplankton during sensing and acclimation to changes in their environment. Our overarching objective is to unravel the role of infochemicals and related gene products in regulating phytoplankton surveillance systems in response to environmental stress conditions. We will focus on the three major biotic interactions of key dominant algal groups in the oceans; intercellular signaling in diatoms, host-virus interactions in coccolithophores and predator-prey interactions. We will provide a suite of cellular probes and metabolic biomarkers that will allow in situ detection of chemical signaling and biotic interactions in the oceans and will highlight their role in shaping microbial food webs. Our vision is to provide novel cellular concepts and molecular tools to the link between the intricate mechanisms of cell signaling and stress response, and large biogeochemical cycles.
Max ERC Funding
1 999 648 €
Duration
Start date: 2011-11-01, End date: 2016-10-31
