Project acronym EVOLOME
Project Genetic and phenotypic precursors of antibiotic resistance in evolving bacterial populations: from single cell to population level analyses
Researcher (PI) Nathalie Balaban
Host Institution (HI) THE HEBREW UNIVERSITY OF JERUSALEM
Call Details Starting Grant (StG), LS8, ERC-2010-StG_20091118
Summary Soon after new antibiotics are introduced, bacterial strains resistant to their action emerge. Recently, non-specific factors that promote the later appearance of specific mechanisms of resistance have been found. Some of these so-called global factors (as opposed to specific resistance mechanisms) emerge as major players in shaping the rate of evolution of resistance. For example, a mutation in the mismatch repair system is a global genetic factor that increases the mutation rate and therefore leads to an increased probability to evolve resistance.
In addition to global genetic factors, it is becoming clear that global phenotypic factors play a crucial role in resistance evolution. For example, activation of stress responses can also result in an elevated mutation rate and accelerated evolution of drug resistance. A natural question which arises in this context is how sub-populations of phenotypic variants differ in their evolutionary potential, and how that, in turn, affects the rate at which an entire population adapts to antibiotic stress.
I propose a multidisciplinary approach to the systematic and quantitative study of the non-specific factors that affect the mode and tempo of evolution towards antibiotic resistance. Our preliminary results indicate that the presence of dormant bacteria that survive antibiotic treatment affects the rate of resistance evolution in bacterial populations. I will exploit the established expertise of my lab using microfluidic devices for single cell analyses to track the emergence of resistance at the single-cell level, in real-time, and to study the correlation between the phenotype of single bacteria and the probability to evolve resistance. My second approach will take advantage of the recent developments in experimental evolution and high throughput sequencing and combine those with single cells observations for the systematic search of E.coli genes that affect the rate of resistance evolution. We will study replicate populations of E.coli, founded by either laboratory strains or clinical isolates, as they evolve in parallel, under antibiotic stress. Evolved populations will be compared with ancestral populations in order to identify genes and phenotypes that have changed during the evolution of antibiotic resistance. Finally, in silico evolution that simulates the experimental conditions will be developed to analyze the contribution of global factors on resistance evolution.
The evolution of antibiotic resistance is not only a fascinating demonstration of the power of evolution but also represents one of the major health threats today. I anticipate that this multidisciplinary study of the global factors that influence the evolution of resistance, from the single cell to the population level, will shed light on the mechanisms used by bacteria to accelerate evolution in general, as well as provide clues as to how to prevent the emergence of antibiotic resistance.
Summary
Soon after new antibiotics are introduced, bacterial strains resistant to their action emerge. Recently, non-specific factors that promote the later appearance of specific mechanisms of resistance have been found. Some of these so-called global factors (as opposed to specific resistance mechanisms) emerge as major players in shaping the rate of evolution of resistance. For example, a mutation in the mismatch repair system is a global genetic factor that increases the mutation rate and therefore leads to an increased probability to evolve resistance.
In addition to global genetic factors, it is becoming clear that global phenotypic factors play a crucial role in resistance evolution. For example, activation of stress responses can also result in an elevated mutation rate and accelerated evolution of drug resistance. A natural question which arises in this context is how sub-populations of phenotypic variants differ in their evolutionary potential, and how that, in turn, affects the rate at which an entire population adapts to antibiotic stress.
I propose a multidisciplinary approach to the systematic and quantitative study of the non-specific factors that affect the mode and tempo of evolution towards antibiotic resistance. Our preliminary results indicate that the presence of dormant bacteria that survive antibiotic treatment affects the rate of resistance evolution in bacterial populations. I will exploit the established expertise of my lab using microfluidic devices for single cell analyses to track the emergence of resistance at the single-cell level, in real-time, and to study the correlation between the phenotype of single bacteria and the probability to evolve resistance. My second approach will take advantage of the recent developments in experimental evolution and high throughput sequencing and combine those with single cells observations for the systematic search of E.coli genes that affect the rate of resistance evolution. We will study replicate populations of E.coli, founded by either laboratory strains or clinical isolates, as they evolve in parallel, under antibiotic stress. Evolved populations will be compared with ancestral populations in order to identify genes and phenotypes that have changed during the evolution of antibiotic resistance. Finally, in silico evolution that simulates the experimental conditions will be developed to analyze the contribution of global factors on resistance evolution.
The evolution of antibiotic resistance is not only a fascinating demonstration of the power of evolution but also represents one of the major health threats today. I anticipate that this multidisciplinary study of the global factors that influence the evolution of resistance, from the single cell to the population level, will shed light on the mechanisms used by bacteria to accelerate evolution in general, as well as provide clues as to how to prevent the emergence of antibiotic resistance.
Max ERC Funding
1 458 200 €
Duration
Start date: 2010-11-01, End date: 2015-10-31
Project acronym HOR.MOON
Project Moonlight-dependent Hormones Orchestrating Lunar Reproductive Periodicity and Regeneration
Researcher (PI) Florian Raible
Host Institution (HI) UNIVERSITAT WIEN
Call Details Starting Grant (StG), LS8, ERC-2010-StG_20091118
Summary The moon governs reproductive cycles in a broad range of marine animals, including cnidarians, polychaetes, crustaceans, echinoderms and fishes. Even outside the animals, lunar reproductive cycles have been described, such as in brown algae or foraminifers. Despite their fundamental nature, and decades of classical observations, close to nothing is known about the molecular processes that underly these lunar reproductive cycles.
We will take advantage of the recent advance in molecular resources and tools in the bristle worm Platynereis dumerilii, which has long served as a key model for classical experimental studies on lunar periodicity. The combination of modern techniques with well-founded classical observations will allow us to decipher, for the first time, the hormonal cues that are regulated by the lunar cycle and are responsible for the orchestration of gonadal maturation and trunk regeneration.
The project builds on established methodology, as well as on the first results of a successful pioneer screen and has three major aims:
(1) the functional investigation of two hormones we recently identified to be under lunar cycle control.
(2) the extension of our successful pioneer screen to understand to which extent other neurohormonal components change over the lunar phase.
(3) the identification of the elusive inhibitory brain hormone that directly acts on the gonads to inhibit premature maturation.
Together, these experiments will lead us to first significant insights into the molecular nature of the hormonal network that underlies moonlight-dependent periodicity and regeneration.
Summary
The moon governs reproductive cycles in a broad range of marine animals, including cnidarians, polychaetes, crustaceans, echinoderms and fishes. Even outside the animals, lunar reproductive cycles have been described, such as in brown algae or foraminifers. Despite their fundamental nature, and decades of classical observations, close to nothing is known about the molecular processes that underly these lunar reproductive cycles.
We will take advantage of the recent advance in molecular resources and tools in the bristle worm Platynereis dumerilii, which has long served as a key model for classical experimental studies on lunar periodicity. The combination of modern techniques with well-founded classical observations will allow us to decipher, for the first time, the hormonal cues that are regulated by the lunar cycle and are responsible for the orchestration of gonadal maturation and trunk regeneration.
The project builds on established methodology, as well as on the first results of a successful pioneer screen and has three major aims:
(1) the functional investigation of two hormones we recently identified to be under lunar cycle control.
(2) the extension of our successful pioneer screen to understand to which extent other neurohormonal components change over the lunar phase.
(3) the identification of the elusive inhibitory brain hormone that directly acts on the gonads to inhibit premature maturation.
Together, these experiments will lead us to first significant insights into the molecular nature of the hormonal network that underlies moonlight-dependent periodicity and regeneration.
Max ERC Funding
1 500 000 €
Duration
Start date: 2010-12-01, End date: 2016-07-31
Project acronym MEDEA
Project Microbial Ecology of the DEep Atlantic pelagic realm
Researcher (PI) Gerhard Herndl
Host Institution (HI) UNIVERSITAT WIEN
Call Details Advanced Grant (AdG), LS8, ERC-2010-AdG_20100317
Summary The project aims at elucidating a major enigma in microbial ecology, i.e., the metabolic activity of prokaryotic communities in the deep sea under in situ pressure conditions, rather than under surface pressure conditions, as commonly done. Analysis of the global data set of prokaryotic abundance indicates that about 40% of prokaryotes reside in depth below 1000m depth with a phylogenetic composition different from that in surface waters. Using a recently fabricated high-pressure sampling and incubation system in combination with advanced tools to assess phylogenetic diversity, gene expression and single-cell activity, we will be able to resolve this enigma on a prokaryotic community level as well as on a phylotype level. This detailed knowledge on the distribution of the auto- and heterotrophic activity of deep-sea prokaryotes under in situ pressure conditions is essential to refine our view on the oceanic biogeochemical cycles, and to obtain a mechanistic understanding of the functioning of deep-sea microbial food webs.
Summary
The project aims at elucidating a major enigma in microbial ecology, i.e., the metabolic activity of prokaryotic communities in the deep sea under in situ pressure conditions, rather than under surface pressure conditions, as commonly done. Analysis of the global data set of prokaryotic abundance indicates that about 40% of prokaryotes reside in depth below 1000m depth with a phylogenetic composition different from that in surface waters. Using a recently fabricated high-pressure sampling and incubation system in combination with advanced tools to assess phylogenetic diversity, gene expression and single-cell activity, we will be able to resolve this enigma on a prokaryotic community level as well as on a phylotype level. This detailed knowledge on the distribution of the auto- and heterotrophic activity of deep-sea prokaryotes under in situ pressure conditions is essential to refine our view on the oceanic biogeochemical cycles, and to obtain a mechanistic understanding of the functioning of deep-sea microbial food webs.
Max ERC Funding
2 500 000 €
Duration
Start date: 2011-07-01, End date: 2016-06-30
