Project acronym 100 Archaic Genomes
Project Genome sequences from extinct hominins
Researcher (PI) Svante PÄÄBO
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), LS2, ERC-2015-AdG
Summary Neandertals and Denisovans, an Asian group distantly related to Neandertals, are the closest evolutionary relatives of present-day humans. They are thus of direct relevance for understanding the origin of modern humans and how modern humans differ from their closest relatives. We will generate genome-wide data from a large number of Neandertal and Denisovan individuals from across their geographical and temporal range as well as from other extinct hominin groups which we may discover. This will be possible by automating highly sensitive approaches to ancient DNA extraction and DNA libraries construction that we have developed so that they can be applied to many specimens from many sites in order to identify those that contain retrievable DNA. Whenever possible we will sequence whole genomes and in other cases use DNA capture methods to generate high-quality data from representative parts of the genome. This will allow us to study the population history of Neandertals and Denisovans, elucidate how many times and where these extinct hominins contributed genes to present-day people, and the extent to which modern humans and archaic groups contributed genetically to Neandertals and Denisovans. By retrieving DNA from specimens that go back to the Middle Pleistocene we will furthermore shed light on the early history and origins of Neandertals and Denisovans.
Summary
Neandertals and Denisovans, an Asian group distantly related to Neandertals, are the closest evolutionary relatives of present-day humans. They are thus of direct relevance for understanding the origin of modern humans and how modern humans differ from their closest relatives. We will generate genome-wide data from a large number of Neandertal and Denisovan individuals from across their geographical and temporal range as well as from other extinct hominin groups which we may discover. This will be possible by automating highly sensitive approaches to ancient DNA extraction and DNA libraries construction that we have developed so that they can be applied to many specimens from many sites in order to identify those that contain retrievable DNA. Whenever possible we will sequence whole genomes and in other cases use DNA capture methods to generate high-quality data from representative parts of the genome. This will allow us to study the population history of Neandertals and Denisovans, elucidate how many times and where these extinct hominins contributed genes to present-day people, and the extent to which modern humans and archaic groups contributed genetically to Neandertals and Denisovans. By retrieving DNA from specimens that go back to the Middle Pleistocene we will furthermore shed light on the early history and origins of Neandertals and Denisovans.
Max ERC Funding
2 350 000 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym ABYSS
Project ABYSS - Assessment of bacterial life and matter cycling in deep-sea surface sediments
Researcher (PI) Antje Boetius
Host Institution (HI) ALFRED-WEGENER-INSTITUT HELMHOLTZ-ZENTRUM FUR POLAR- UND MEERESFORSCHUNG
Call Details Advanced Grant (AdG), LS8, ERC-2011-ADG_20110310
Summary The deep-sea floor hosts a distinct microbial biome covering 67% of the Earth’s surface, characterized by cold temperatures, permanent darkness, high pressure and food limitation. The surface sediments are dominated by bacteria, with on average a billion cells per ml. Benthic bacteria are highly relevant to the Earth’s element cycles as they remineralize most of the organic matter sinking from the productive surface ocean, and return nutrients, thereby promoting ocean primary production. What passes the bacterial filter is a relevant sink for carbon on geological time scales, influencing global oxygen and carbon budgets, and fueling the deep subsurface biosphere. Despite the relevance of deep-sea sediment bacteria to climate, geochemical cycles and ecology of the seafloor, their genetic and functional diversity, niche differentiation and biological interactions remain unknown. Our preliminary work in a global survey of deep-sea sediments enables us now to target specific genes for the quantification of abyssal bacteria. We can trace isotope-labeled elements into communities and single cells, and analyze the molecular alteration of organic matter during microbial degradation, all in context with environmental dynamics recorded at the only long-term deep-sea ecosystem observatory in the Arctic that we maintain. I propose to bridge biogeochemistry, ecology, microbiology and marine biology to develop a systematic understanding of abyssal sediment bacterial community distribution, diversity, function and interactions, by combining in situ flux studies and different visualization techniques with a wide range of molecular tools. Substantial progress is expected in understanding I) identity and function of the dominant types of indigenous benthic bacteria, II) dynamics in bacterial activity and diversity caused by variations in particle flux, III) interactions with different types and ages of organic matter, and other biological factors.
Summary
The deep-sea floor hosts a distinct microbial biome covering 67% of the Earth’s surface, characterized by cold temperatures, permanent darkness, high pressure and food limitation. The surface sediments are dominated by bacteria, with on average a billion cells per ml. Benthic bacteria are highly relevant to the Earth’s element cycles as they remineralize most of the organic matter sinking from the productive surface ocean, and return nutrients, thereby promoting ocean primary production. What passes the bacterial filter is a relevant sink for carbon on geological time scales, influencing global oxygen and carbon budgets, and fueling the deep subsurface biosphere. Despite the relevance of deep-sea sediment bacteria to climate, geochemical cycles and ecology of the seafloor, their genetic and functional diversity, niche differentiation and biological interactions remain unknown. Our preliminary work in a global survey of deep-sea sediments enables us now to target specific genes for the quantification of abyssal bacteria. We can trace isotope-labeled elements into communities and single cells, and analyze the molecular alteration of organic matter during microbial degradation, all in context with environmental dynamics recorded at the only long-term deep-sea ecosystem observatory in the Arctic that we maintain. I propose to bridge biogeochemistry, ecology, microbiology and marine biology to develop a systematic understanding of abyssal sediment bacterial community distribution, diversity, function and interactions, by combining in situ flux studies and different visualization techniques with a wide range of molecular tools. Substantial progress is expected in understanding I) identity and function of the dominant types of indigenous benthic bacteria, II) dynamics in bacterial activity and diversity caused by variations in particle flux, III) interactions with different types and ages of organic matter, and other biological factors.
Max ERC Funding
3 375 693 €
Duration
Start date: 2012-06-01, End date: 2018-05-31
Project acronym ACCOMPLI
Project Assembly and maintenance of a co-regulated chromosomal compartment
Researcher (PI) Peter Burkhard Becker
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), LS2, ERC-2011-ADG_20110310
Summary "Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment.
The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation.
We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis.
Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex."
Summary
"Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment.
The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation.
We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis.
Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex."
Max ERC Funding
2 482 770 €
Duration
Start date: 2012-02-01, End date: 2017-01-31
Project acronym AMAREC
Project Amenability, Approximation and Reconstruction
Researcher (PI) Wilhelm WINTER
Host Institution (HI) WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER
Call Details Advanced Grant (AdG), PE1, ERC-2018-ADG
Summary Algebras of operators on Hilbert spaces were originally introduced as the right framework for the mathematical description of quantum mechanics. In modern mathematics the scope has much broadened due to the highly versatile nature of operator algebras. They are particularly useful in the analysis of groups and their actions. Amenability is a finiteness property which occurs in many different contexts and which can be characterised in many different ways. We will analyse amenability in terms of approximation properties, in the frameworks of abstract C*-algebras, of topological dynamical systems, and of discrete groups. Such approximation properties will serve as bridging devices between these setups, and they will be used to systematically recover geometric information about the underlying structures. When passing from groups, and more generally from dynamical systems, to operator algebras, one loses information, but one gains new tools to isolate and analyse pertinent properties of the underlying structure. We will mostly be interested in the topological setting, and in the associated C*-algebras. Amenability of groups or of dynamical systems then translates into the completely positive approximation property. Systems of completely positive approximations store all the essential data about a C*-algebra, and sometimes one can arrange the systems so that one can directly read of such information. For transformation group C*-algebras, one can achieve this by using approximation properties of the underlying dynamics. To some extent one can even go back, and extract dynamical approximation properties from completely positive approximations of the C*-algebra. This interplay between approximation properties in topological dynamics and in noncommutative topology carries a surprisingly rich structure. It connects directly to the heart of the classification problem for nuclear C*-algebras on the one hand, and to central open questions on amenable dynamics on the other.
Summary
Algebras of operators on Hilbert spaces were originally introduced as the right framework for the mathematical description of quantum mechanics. In modern mathematics the scope has much broadened due to the highly versatile nature of operator algebras. They are particularly useful in the analysis of groups and their actions. Amenability is a finiteness property which occurs in many different contexts and which can be characterised in many different ways. We will analyse amenability in terms of approximation properties, in the frameworks of abstract C*-algebras, of topological dynamical systems, and of discrete groups. Such approximation properties will serve as bridging devices between these setups, and they will be used to systematically recover geometric information about the underlying structures. When passing from groups, and more generally from dynamical systems, to operator algebras, one loses information, but one gains new tools to isolate and analyse pertinent properties of the underlying structure. We will mostly be interested in the topological setting, and in the associated C*-algebras. Amenability of groups or of dynamical systems then translates into the completely positive approximation property. Systems of completely positive approximations store all the essential data about a C*-algebra, and sometimes one can arrange the systems so that one can directly read of such information. For transformation group C*-algebras, one can achieve this by using approximation properties of the underlying dynamics. To some extent one can even go back, and extract dynamical approximation properties from completely positive approximations of the C*-algebra. This interplay between approximation properties in topological dynamics and in noncommutative topology carries a surprisingly rich structure. It connects directly to the heart of the classification problem for nuclear C*-algebras on the one hand, and to central open questions on amenable dynamics on the other.
Max ERC Funding
1 596 017 €
Duration
Start date: 2019-10-01, End date: 2024-09-30
Project acronym ANAMULTISCALE
Project Analysis of Multiscale Systems Driven by Functionals
Researcher (PI) Alexander Mielke
Host Institution (HI) FORSCHUNGSVERBUND BERLIN EV
Call Details Advanced Grant (AdG), PE1, ERC-2010-AdG_20100224
Summary Many complex phenomena in the sciences are described by nonlinear partial differential equations, the solutions of which exhibit oscillations and concentration effects on multiple temporal or spatial scales. Our aim is to use methods from applied analysis to contribute to the understanding of the interplay of effects on different scales. The central question is to determine those quantities on the microscale which are needed to for the correct description of the macroscopic evolution.
We aim to develop a mathematical framework for analyzing and modeling coupled systems with multiple scales. This will include Hamiltonian dynamics as well as different types of dissipation like gradient flows or rate-independent dynamics. The choice of models will be guided by specific applications in material modeling (e.g., thermoplasticity, pattern formation, porous media) and optoelectronics (pulse interaction, Maxwell-Bloch systems, semiconductors, quantum mechanics). The research will address mathematically fundamental issues like existence and stability of solutions but will mainly be devoted to the modeling of multiscale phenomena in evolution systems. We will focus on systems with geometric structures, where the dynamics is driven by functionals. Thus, we can go much beyond the classical theory of homogenization and singular perturbations. The novel features of our approach are
- the combination of different dynamical effects in one framework,
- the use of geometric and metric structures for coupled partial differential equations,
- the exploitation of Gamma-convergence for evolution systems driven by functionals.
Summary
Many complex phenomena in the sciences are described by nonlinear partial differential equations, the solutions of which exhibit oscillations and concentration effects on multiple temporal or spatial scales. Our aim is to use methods from applied analysis to contribute to the understanding of the interplay of effects on different scales. The central question is to determine those quantities on the microscale which are needed to for the correct description of the macroscopic evolution.
We aim to develop a mathematical framework for analyzing and modeling coupled systems with multiple scales. This will include Hamiltonian dynamics as well as different types of dissipation like gradient flows or rate-independent dynamics. The choice of models will be guided by specific applications in material modeling (e.g., thermoplasticity, pattern formation, porous media) and optoelectronics (pulse interaction, Maxwell-Bloch systems, semiconductors, quantum mechanics). The research will address mathematically fundamental issues like existence and stability of solutions but will mainly be devoted to the modeling of multiscale phenomena in evolution systems. We will focus on systems with geometric structures, where the dynamics is driven by functionals. Thus, we can go much beyond the classical theory of homogenization and singular perturbations. The novel features of our approach are
- the combination of different dynamical effects in one framework,
- the use of geometric and metric structures for coupled partial differential equations,
- the exploitation of Gamma-convergence for evolution systems driven by functionals.
Max ERC Funding
1 390 000 €
Duration
Start date: 2011-04-01, End date: 2017-03-31
Project acronym ARCID
Project The Role of Arl Proteins in Retinal and other Ciliary Diseases
Researcher (PI) Alfred Wittinghofer
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), LS1, ERC-2010-AdG_20100317
Summary Arl (Arf-like) proteins, GTP-binding proteins of the Ras superfamily, are molecular switches that cycle between a GDP-bound inactive and GTP-bound active state. There are 16 members of the Arl subfamily in the human genome whose basic mechanistic function is unknown. The interactome of Arl2/3 includes proteins involved in retinopathies and other ciliary diseases such as Leber¿s Congenital Amaurosis (LCA) and kidney diseases such as nephronophthisis. Arl6 has been found mutated in Bardet Biedl Syndrome, another pleiotropic ciliary disease. In the proposed interdisciplinary project I want to explore the function of the protein network of Arl2/3 and Arl6 by a combination of biochemical, biophysical and structural methods and use the knowledge obtained to probe their function in live cells. As with other subfamily proteins of the Ras superfamily which have been found to mediate similar biological functions I want to derive a basic understanding of the function of Arl proteins and how it relates to the development and function of the ciliary organelle and how they contribute to ciliary diseases. The molecules in the focus of the project are: the GTP-binding proteins Arl2, 3, 6; RP2, an Arl3GAP mutated in Retinitis pigmentosa; Regulators of Arl2 and 3; PDE¿ and HRG4, effectors of Arl2/3, which bind lipidated proteins; RPGR, mutated in Retinitis pigmentosa, an interactor of PDE¿; RPGRIP and RPGRIPL, interactors of RPGR mutated in LCA and other ciliopathies; Nephrocystin, mutated in nephronophthisis, an interactor of RPGRIP and Arl6, mutated in Bardet Biedl Syndrome, and the BBS complex. The working hypothesis is that Arl protein network(s) mediate ciliary transport processes and that the GTP switch cycle of Arl proteins is an important element of regulation of these processes.
Summary
Arl (Arf-like) proteins, GTP-binding proteins of the Ras superfamily, are molecular switches that cycle between a GDP-bound inactive and GTP-bound active state. There are 16 members of the Arl subfamily in the human genome whose basic mechanistic function is unknown. The interactome of Arl2/3 includes proteins involved in retinopathies and other ciliary diseases such as Leber¿s Congenital Amaurosis (LCA) and kidney diseases such as nephronophthisis. Arl6 has been found mutated in Bardet Biedl Syndrome, another pleiotropic ciliary disease. In the proposed interdisciplinary project I want to explore the function of the protein network of Arl2/3 and Arl6 by a combination of biochemical, biophysical and structural methods and use the knowledge obtained to probe their function in live cells. As with other subfamily proteins of the Ras superfamily which have been found to mediate similar biological functions I want to derive a basic understanding of the function of Arl proteins and how it relates to the development and function of the ciliary organelle and how they contribute to ciliary diseases. The molecules in the focus of the project are: the GTP-binding proteins Arl2, 3, 6; RP2, an Arl3GAP mutated in Retinitis pigmentosa; Regulators of Arl2 and 3; PDE¿ and HRG4, effectors of Arl2/3, which bind lipidated proteins; RPGR, mutated in Retinitis pigmentosa, an interactor of PDE¿; RPGRIP and RPGRIPL, interactors of RPGR mutated in LCA and other ciliopathies; Nephrocystin, mutated in nephronophthisis, an interactor of RPGRIP and Arl6, mutated in Bardet Biedl Syndrome, and the BBS complex. The working hypothesis is that Arl protein network(s) mediate ciliary transport processes and that the GTP switch cycle of Arl proteins is an important element of regulation of these processes.
Max ERC Funding
2 434 400 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym ATMMACHINE
Project Structural mechanism of recognition, signaling and resection of DNA double-strand breaks
Researcher (PI) Karl-Peter Hopfner
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), LS1, ERC-2012-ADG_20120314
Summary DNA double-strand breaks are perhaps the most harmful DNA damages and result in carcinogenic chromosome aberrations. Cells protect their genome by activating a complex signaling and repair network, collectively denoted DNA damage response (DDR). A key initial step of the DDR is the activation of the 360 kDa checkpoint kinase ATM (ataxia telangiectasia mutated) by the multifunctional DSB repair factor Mre11-Rad50-Nbs1 (MRN). MRN senses and tethers DSBs, processes DSBs for further resection, and recruits and activates ATM to trigger the DDR. A mechanistic basis for the activities of the core DDR sensor MRN has not been established, despite intense research over the past decade. Our recent breakthroughs on structures of core Mre11-Rad50 and Mre11-Nbs1 complexes enable us now address three central questions to finally clarify the mechanism of MRN in the DDR:
- How does MRN interact with DNA or DNA ends in an ATP dependent manner?
- How do MRN and associated factors such as CtIP process blocked DNA ends?
- How do MRN and DNA activate ATM?
We will employ an innovative structural biology hybrid methods approach by combining X-ray crystallography, electron microscopy and small angle scattering with crosslink mass spectrometry and combine the structure-oriented techniques with validating in vitro and in vivo functional studies. The anticipated outcome will clarify the structural mechanism of one of the most important but enigmatic molecular machineries in maintaining genome stability and also help understand the molecular defects associated with several prominent cancer predisposition and neurodegenerative disorders.
Summary
DNA double-strand breaks are perhaps the most harmful DNA damages and result in carcinogenic chromosome aberrations. Cells protect their genome by activating a complex signaling and repair network, collectively denoted DNA damage response (DDR). A key initial step of the DDR is the activation of the 360 kDa checkpoint kinase ATM (ataxia telangiectasia mutated) by the multifunctional DSB repair factor Mre11-Rad50-Nbs1 (MRN). MRN senses and tethers DSBs, processes DSBs for further resection, and recruits and activates ATM to trigger the DDR. A mechanistic basis for the activities of the core DDR sensor MRN has not been established, despite intense research over the past decade. Our recent breakthroughs on structures of core Mre11-Rad50 and Mre11-Nbs1 complexes enable us now address three central questions to finally clarify the mechanism of MRN in the DDR:
- How does MRN interact with DNA or DNA ends in an ATP dependent manner?
- How do MRN and associated factors such as CtIP process blocked DNA ends?
- How do MRN and DNA activate ATM?
We will employ an innovative structural biology hybrid methods approach by combining X-ray crystallography, electron microscopy and small angle scattering with crosslink mass spectrometry and combine the structure-oriented techniques with validating in vitro and in vivo functional studies. The anticipated outcome will clarify the structural mechanism of one of the most important but enigmatic molecular machineries in maintaining genome stability and also help understand the molecular defects associated with several prominent cancer predisposition and neurodegenerative disorders.
Max ERC Funding
2 498 019 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym BathyBiome
Project The Symbiome of Bathymodiolus Mussels from Hydrothermal Vents: From the Genome
to the Environment
Researcher (PI) Nicole Dubilier
Host Institution (HI) MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Call Details Advanced Grant (AdG), LS8, ERC-2013-ADG
Summary The discovery of deep-sea hydrothermal vents in 1977 was one of the most profound findings of the 20th century, revolutionizing our perception of energy sources fueling primary productivity on Earth. These ecosystems are based on chemosynthesis, that is the fixation of carbon dioxide into organic compounds as in photosynthesis, but using inorganic compounds such as sulfide, methane or hydrogen, as energy sources instead of sunlight. Hydrothermal vents support tremendous biomass and productivity of which the majority is generated through symbiotic microbe-animal associations. Bathymodiolus mussels are able to build extraordinarily large and productive communities at hydrothermal vents because they harbor symbiotic bacteria that use inorganic energy sources from the vent fluids to feed their hosts via carbon fixation. In addition to their beneficial symbionts, the mussels are infected by a novel bacterial parasite that exclusively invades and multiplies in their nuclei. In the work proposed here, I will use a wide array of tools that range from deep-sea in situ instruments to sophisticated molecular, 'omic' and imaging analyses to study the microbiome associated with Bathymodiolus mussels. The proposed
research bridges biogeochemistry, ecological and evolutionary biology, and molecular microbiology to develop a systematic understanding of the symbiotic interactions between microbes, their hosts, and their environment in one of the most extreme and fascinating habitats on Earth, hydrothermal vents.
Summary
The discovery of deep-sea hydrothermal vents in 1977 was one of the most profound findings of the 20th century, revolutionizing our perception of energy sources fueling primary productivity on Earth. These ecosystems are based on chemosynthesis, that is the fixation of carbon dioxide into organic compounds as in photosynthesis, but using inorganic compounds such as sulfide, methane or hydrogen, as energy sources instead of sunlight. Hydrothermal vents support tremendous biomass and productivity of which the majority is generated through symbiotic microbe-animal associations. Bathymodiolus mussels are able to build extraordinarily large and productive communities at hydrothermal vents because they harbor symbiotic bacteria that use inorganic energy sources from the vent fluids to feed their hosts via carbon fixation. In addition to their beneficial symbionts, the mussels are infected by a novel bacterial parasite that exclusively invades and multiplies in their nuclei. In the work proposed here, I will use a wide array of tools that range from deep-sea in situ instruments to sophisticated molecular, 'omic' and imaging analyses to study the microbiome associated with Bathymodiolus mussels. The proposed
research bridges biogeochemistry, ecological and evolutionary biology, and molecular microbiology to develop a systematic understanding of the symbiotic interactions between microbes, their hosts, and their environment in one of the most extreme and fascinating habitats on Earth, hydrothermal vents.
Max ERC Funding
2 499 122 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym CANCERBIOME
Project Cancerbiome: Characterization of the cancer-associated microbiome
Researcher (PI) Peer Bork
Host Institution (HI) EUROPEAN MOLECULAR BIOLOGY LABORATORY
Call Details Advanced Grant (AdG), LS2, ERC-2010-AdG_20100317
Summary Deep environmental sequencing (metagenomics) will be used to characterize microbial communities associated with 3 different cancer types: cervical cancer, oral squamous cell carcinoma and colorectal cancer. For all 3 types, non-invasive molecular diagnostics and prognostics are feasible via utilization of vaginal, oral and faecal samples, respectively. The project consequently aims to identify microbial markers in these ¿readouts¿ that correlate with cancer presence or progression. Microbial markers can be individual species or specific community compositions, but also particular genes or pathways. The microbial communities will be sampled locally at tumor surfaces and in healthy control tissues. After DNA extraction and sequencing, a complex bioinformatics pipeline will be developed to characterise the microbiomes and to identify the cancer-specific functional and phylogenetic markers therein. For colorectal cancer, the project intends to go into more details in that it tries i) to establish a correlation of microbiota with cancer progression and it ii) explores differences between distinct cancer subtypes. For each of the 3 cancer types, at least two samples from 40 individuals will be sequenced (as well as controls) at a depth of at least 5Gb each using Illumina technology. This is expected to be sufficient for the identification of microbial markers and also allows superficial genotyping of the individuals at ca 2-3x coverage as a by-product (the samples will contain considerable amounts of human DNA). Further analyses will be designed to study the potential of certain microbial species or community compositions to enhance or even cause one or more of the 3 cancers. The discovery of such causations will open up research towards directed antimicrobial treatment.
Summary
Deep environmental sequencing (metagenomics) will be used to characterize microbial communities associated with 3 different cancer types: cervical cancer, oral squamous cell carcinoma and colorectal cancer. For all 3 types, non-invasive molecular diagnostics and prognostics are feasible via utilization of vaginal, oral and faecal samples, respectively. The project consequently aims to identify microbial markers in these ¿readouts¿ that correlate with cancer presence or progression. Microbial markers can be individual species or specific community compositions, but also particular genes or pathways. The microbial communities will be sampled locally at tumor surfaces and in healthy control tissues. After DNA extraction and sequencing, a complex bioinformatics pipeline will be developed to characterise the microbiomes and to identify the cancer-specific functional and phylogenetic markers therein. For colorectal cancer, the project intends to go into more details in that it tries i) to establish a correlation of microbiota with cancer progression and it ii) explores differences between distinct cancer subtypes. For each of the 3 cancer types, at least two samples from 40 individuals will be sequenced (as well as controls) at a depth of at least 5Gb each using Illumina technology. This is expected to be sufficient for the identification of microbial markers and also allows superficial genotyping of the individuals at ca 2-3x coverage as a by-product (the samples will contain considerable amounts of human DNA). Further analyses will be designed to study the potential of certain microbial species or community compositions to enhance or even cause one or more of the 3 cancers. The discovery of such causations will open up research towards directed antimicrobial treatment.
Max ERC Funding
2 233 740 €
Duration
Start date: 2011-07-01, End date: 2016-06-30
Project acronym CelluFuel
Project Designer Cellulosomes by Single Molecule Cut & Paste
Researcher (PI) Hermann Eduard Gaub
Host Institution (HI) LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Call Details Advanced Grant (AdG), LS1, ERC-2011-ADG_20110310
Summary Biofuel from wood and waste will be a substantial share of our future energy mix. The conversion of lignocellulose to fermentable polysaccharides is the current bottleneck. We propose to use single molecule cut and paste technology to assemble designer cellulosoms and combine enzymes from different species with nanocatalysts.
Summary
Biofuel from wood and waste will be a substantial share of our future energy mix. The conversion of lignocellulose to fermentable polysaccharides is the current bottleneck. We propose to use single molecule cut and paste technology to assemble designer cellulosoms and combine enzymes from different species with nanocatalysts.
Max ERC Funding
2 351 450 €
Duration
Start date: 2012-03-01, End date: 2018-02-28