Project acronym 1st-principles-discs
Project A First Principles Approach to Accretion Discs
Researcher (PI) Martin Elias Pessah
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), PE9, ERC-2012-StG_20111012
Summary Most celestial bodies, from planets, to stars, to black holes; gain mass during their lives by means of an accretion disc. Understanding the physical processes that determine the rate at which matter accretes and energy is radiated in these discs is vital for unraveling the formation, evolution, and fate of almost every type of object in the Universe. Despite the fact that magnetic fields have been known to be crucial in accretion discs since the early 90’s, the majority of astrophysical questions that depend on the details of how disc accretion proceeds are still being addressed using the “standard” accretion disc model (developed in the early 70’s), where magnetic fields do not play an explicit role. This has prevented us from fully exploring the astrophysical consequences and observational signatures of realistic accretion disc models, leading to a profound disconnect between observations (usually interpreted with the standard paradigm) and modern accretion disc theory and numerical simulations (where magnetic turbulence is crucial). The goal of this proposal is to use several complementary approaches in order to finally move beyond the standard paradigm. This program has two main objectives: 1) Develop the theoretical framework to incorporate magnetic fields, and the ensuing turbulence, into self-consistent accretion disc models, and investigate their observational implications. 2) Investigate transport and radiative processes in collision-less disc regions, where non-thermal radiation originates, by employing a kinetic particle description of the plasma. In order to achieve these goals, we will use, and build upon, state-of-the-art magnetohydrodynamic and particle-in-cell codes in conjunction with theoretical modeling. This framework will make it possible to address fundamental questions on stellar and planet formation, binary systems with a compact object, and supermassive black hole feedback in a way that has no counterpart within the standard paradigm.
Summary
Most celestial bodies, from planets, to stars, to black holes; gain mass during their lives by means of an accretion disc. Understanding the physical processes that determine the rate at which matter accretes and energy is radiated in these discs is vital for unraveling the formation, evolution, and fate of almost every type of object in the Universe. Despite the fact that magnetic fields have been known to be crucial in accretion discs since the early 90’s, the majority of astrophysical questions that depend on the details of how disc accretion proceeds are still being addressed using the “standard” accretion disc model (developed in the early 70’s), where magnetic fields do not play an explicit role. This has prevented us from fully exploring the astrophysical consequences and observational signatures of realistic accretion disc models, leading to a profound disconnect between observations (usually interpreted with the standard paradigm) and modern accretion disc theory and numerical simulations (where magnetic turbulence is crucial). The goal of this proposal is to use several complementary approaches in order to finally move beyond the standard paradigm. This program has two main objectives: 1) Develop the theoretical framework to incorporate magnetic fields, and the ensuing turbulence, into self-consistent accretion disc models, and investigate their observational implications. 2) Investigate transport and radiative processes in collision-less disc regions, where non-thermal radiation originates, by employing a kinetic particle description of the plasma. In order to achieve these goals, we will use, and build upon, state-of-the-art magnetohydrodynamic and particle-in-cell codes in conjunction with theoretical modeling. This framework will make it possible to address fundamental questions on stellar and planet formation, binary systems with a compact object, and supermassive black hole feedback in a way that has no counterpart within the standard paradigm.
Max ERC Funding
1 793 697 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym 3D-PXM
Project 3D Piezoresponse X-ray Microscopy
Researcher (PI) Hugh SIMONS
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Starting Grant (StG), PE3, ERC-2018-STG
Summary Polar materials, such as piezoelectrics and ferroelectrics are essential to our modern life, yet they are mostly developed by trial-and-error. Their properties overwhelmingly depend on the defects within them, the majority of which are hidden in the bulk. The road to better materials is via mapping these defects, but our best tool for it – piezoresponse force microscopy (PFM) – is limited to surfaces. 3D-PXM aims to revolutionize our understanding by measuring the local structure-property correlations around individual defects buried deep in the bulk.
This is a completely new kind of microscopy enabling 3D maps of local strain and polarization (i.e. piezoresponse) with 10 nm resolution in mm-sized samples. It is novel, multi-scale and fast enough to capture defect dynamics in real time. Uniquely, it is a full-field method that uses a synthetic-aperture approach to improve both resolution and recover the image phase. This phase is then quantitatively correlated to local polarization and strain via a forward model. 3D-PXM combines advances in X-Ray optics, phase recovery and data analysis to create something transformative. In principle, it can achieve spatial resolution comparable to the best coherent X-Ray microscopy methods while being faster, used on larger samples, and without risk of radiation damage.
For the first time, this opens the door to solving how defects influence bulk properties under real-life conditions. 3D-PXM focuses on three types of defects prevalent in polar materials: grain boundaries, dislocations and polar nanoregions. Individually they address major gaps in the state-of-the-art, while together making great strides towards fully understanding defects. This understanding is expected to inform a new generation of multi-scale models that can account for a material’s full heterogeneity. These models are the first step towards abandoning our tradition of trial-and-error, and with this comes the potential for a new era of polar materials.
Summary
Polar materials, such as piezoelectrics and ferroelectrics are essential to our modern life, yet they are mostly developed by trial-and-error. Their properties overwhelmingly depend on the defects within them, the majority of which are hidden in the bulk. The road to better materials is via mapping these defects, but our best tool for it – piezoresponse force microscopy (PFM) – is limited to surfaces. 3D-PXM aims to revolutionize our understanding by measuring the local structure-property correlations around individual defects buried deep in the bulk.
This is a completely new kind of microscopy enabling 3D maps of local strain and polarization (i.e. piezoresponse) with 10 nm resolution in mm-sized samples. It is novel, multi-scale and fast enough to capture defect dynamics in real time. Uniquely, it is a full-field method that uses a synthetic-aperture approach to improve both resolution and recover the image phase. This phase is then quantitatively correlated to local polarization and strain via a forward model. 3D-PXM combines advances in X-Ray optics, phase recovery and data analysis to create something transformative. In principle, it can achieve spatial resolution comparable to the best coherent X-Ray microscopy methods while being faster, used on larger samples, and without risk of radiation damage.
For the first time, this opens the door to solving how defects influence bulk properties under real-life conditions. 3D-PXM focuses on three types of defects prevalent in polar materials: grain boundaries, dislocations and polar nanoregions. Individually they address major gaps in the state-of-the-art, while together making great strides towards fully understanding defects. This understanding is expected to inform a new generation of multi-scale models that can account for a material’s full heterogeneity. These models are the first step towards abandoning our tradition of trial-and-error, and with this comes the potential for a new era of polar materials.
Max ERC Funding
1 496 941 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
Project acronym 3S-BTMUC
Project Soft, Slimy, Sliding Interfaces: Biotribological Properties of Mucins and Mucus gels
Researcher (PI) Seunghwan Lee
Host Institution (HI) DANMARKS TEKNISKE UNIVERSITET
Call Details Starting Grant (StG), LS9, ERC-2010-StG_20091118
Summary Mucins are a family of high-molecular-weight glycoproteins and a major macromolecular constituent in slimy mucus gels that are covering the surface of internal biological tissues. A primary role of mucus gels in biological systems is known to be the protection and lubrication of underlying epithelial cell surfaces. This is intuitively well appreciated by both science community and the public, and yet detailed lubrication properties of mucins and mucus gels have remained largely unexplored to date. Detailed and systematic understanding of the lubrication mechanism of mucus gels is significant from many angles; firstly, lubricity of mucus gels is closely related with fundamental functions of various human organs, such as eye blinking, mastication in oral cavity, swallowing through esophagus, digestion in stomach, breathing through air way and respiratory organs, and thus often indicates the health state of those organs. Furthermore, for the application of various tissue-contacting devices or personal care products, e.g. catheters, endoscopes, and contact lenses, mucus gel layer is the first counter surface that comes into the mechanical and tribological contacts with them. Finally, remarkable lubricating performance by mucins and mucus gels in biological systems may provide many useful and possibly innovative hints in utilizing water as base lubricant for man-made engineering systems. This project thus proposes to carry out a 5 year research program focusing on exploring the lubricity of mucins and mucus gels by combining a broad range of experimental approaches in biology and tribology.
Summary
Mucins are a family of high-molecular-weight glycoproteins and a major macromolecular constituent in slimy mucus gels that are covering the surface of internal biological tissues. A primary role of mucus gels in biological systems is known to be the protection and lubrication of underlying epithelial cell surfaces. This is intuitively well appreciated by both science community and the public, and yet detailed lubrication properties of mucins and mucus gels have remained largely unexplored to date. Detailed and systematic understanding of the lubrication mechanism of mucus gels is significant from many angles; firstly, lubricity of mucus gels is closely related with fundamental functions of various human organs, such as eye blinking, mastication in oral cavity, swallowing through esophagus, digestion in stomach, breathing through air way and respiratory organs, and thus often indicates the health state of those organs. Furthermore, for the application of various tissue-contacting devices or personal care products, e.g. catheters, endoscopes, and contact lenses, mucus gel layer is the first counter surface that comes into the mechanical and tribological contacts with them. Finally, remarkable lubricating performance by mucins and mucus gels in biological systems may provide many useful and possibly innovative hints in utilizing water as base lubricant for man-made engineering systems. This project thus proposes to carry out a 5 year research program focusing on exploring the lubricity of mucins and mucus gels by combining a broad range of experimental approaches in biology and tribology.
Max ERC Funding
1 432 920 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym aCROBAT
Project Circadian Regulation Of Brown Adipose Thermogenesis
Researcher (PI) Zachary Philip Gerhart-Hines
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Starting Grant (StG), LS4, ERC-2014-STG
Summary Obesity and diabetes have reached pandemic proportions and new therapeutic strategies are critically needed. Brown adipose tissue (BAT), a major source of heat production, possesses significant energy-dissipating capacity and therefore represents a promising target to use in combating these diseases. Recently, I discovered a novel link between circadian rhythm and thermogenic stress in the control of the conserved, calorie-burning functions of BAT. Circadian and thermogenic signaling to BAT incorporates blood-borne hormonal and nutrient cues with direct neuronal input. Yet how these responses coordinately shape BAT energy-expending potential through the regulation of cell surface receptors, metabolic enzymes, and transcriptional effectors is still not understood. My primary goal is to investigate this previously unappreciated network of crosstalk that allows mammals to effectively orchestrate daily rhythms in BAT metabolism, while maintaining their ability to adapt to abrupt changes in energy demand. My group will address this question using gain and loss-of-function in vitro and in vivo studies, newly-generated mouse models, customized physiological phenotyping, and cutting-edge advances in next generation RNA sequencing and mass spectrometry. Preliminary, small-scale validations of our methodologies have already yielded a number of novel candidates that may drive key facets of BAT metabolism. Additionally, we will extend our circadian and thermogenic studies into humans to evaluate the translational potential. Our results will advance the fundamental understanding of how daily oscillations in bioenergetic networks establish a framework for the anticipation of and adaptation to environmental challenges. Importantly, we expect that these mechanistic insights will reveal pharmacological targets through which we can unlock evolutionary constraints and harness the energy-expending potential of BAT for the prevention and treatment of obesity and diabetes.
Summary
Obesity and diabetes have reached pandemic proportions and new therapeutic strategies are critically needed. Brown adipose tissue (BAT), a major source of heat production, possesses significant energy-dissipating capacity and therefore represents a promising target to use in combating these diseases. Recently, I discovered a novel link between circadian rhythm and thermogenic stress in the control of the conserved, calorie-burning functions of BAT. Circadian and thermogenic signaling to BAT incorporates blood-borne hormonal and nutrient cues with direct neuronal input. Yet how these responses coordinately shape BAT energy-expending potential through the regulation of cell surface receptors, metabolic enzymes, and transcriptional effectors is still not understood. My primary goal is to investigate this previously unappreciated network of crosstalk that allows mammals to effectively orchestrate daily rhythms in BAT metabolism, while maintaining their ability to adapt to abrupt changes in energy demand. My group will address this question using gain and loss-of-function in vitro and in vivo studies, newly-generated mouse models, customized physiological phenotyping, and cutting-edge advances in next generation RNA sequencing and mass spectrometry. Preliminary, small-scale validations of our methodologies have already yielded a number of novel candidates that may drive key facets of BAT metabolism. Additionally, we will extend our circadian and thermogenic studies into humans to evaluate the translational potential. Our results will advance the fundamental understanding of how daily oscillations in bioenergetic networks establish a framework for the anticipation of and adaptation to environmental challenges. Importantly, we expect that these mechanistic insights will reveal pharmacological targets through which we can unlock evolutionary constraints and harness the energy-expending potential of BAT for the prevention and treatment of obesity and diabetes.
Max ERC Funding
1 497 008 €
Duration
Start date: 2015-05-01, End date: 2020-04-30
Project acronym ADAPT
Project Origins and factors governing adaptation: Insights from experimental evolution and population genomic data
Researcher (PI) Thomas, Martin Jean Bataillon
Host Institution (HI) AARHUS UNIVERSITET
Call Details Starting Grant (StG), LS8, ERC-2012-StG_20111109
Summary "I propose a systematic study of the type of genetic variation enabling adaptation and factors that limit rates of adaptation in natural populations. New methods will be developed for analysing data from experimental evolution and population genomics. The methods will be applied to state of the art data from both fields. Adaptation is generated by natural selection sieving through heritable variation. Examples of adaptation are available from the fossil record and from extant populations. Genomic studies have supplied many instances of genomic regions exhibiting footprint of natural selection favouring new variants. Despite ample proof that adaptation happens, we know little about beneficial mutations– the raw stuff enabling adaptation. Is adaptation mediated by genetic variation pre-existing in the population, or by variation supplied de novo through mutations? We know even less about what factors limit rates of adaptation. Answers to these questions are crucial for Evolutionary Biology, but also for believable quantifications of the evolutionary potential of populations. Population genetic theory makes predictions and allows inference from the patterns of polymorphism within species and divergence between species. Yet models specifying the fitness effects of mutations are often missing. Fitness landscape models will be mobilized to fill this gap and develop methods for inferring the distribution of fitness effects and factors governing rates of adaptation. Insights into the processes underlying adaptation will thus be gained from experimental evolution and population genomics data. The applicability of insights gained from experimental evolution to comprehend adaptation in nature will be scrutinized. We will unite two very different approaches for studying adaptation. The project will boost our understanding of how selection shapes genomes and open the way for further quantitative tests of theories of adaptation."
Summary
"I propose a systematic study of the type of genetic variation enabling adaptation and factors that limit rates of adaptation in natural populations. New methods will be developed for analysing data from experimental evolution and population genomics. The methods will be applied to state of the art data from both fields. Adaptation is generated by natural selection sieving through heritable variation. Examples of adaptation are available from the fossil record and from extant populations. Genomic studies have supplied many instances of genomic regions exhibiting footprint of natural selection favouring new variants. Despite ample proof that adaptation happens, we know little about beneficial mutations– the raw stuff enabling adaptation. Is adaptation mediated by genetic variation pre-existing in the population, or by variation supplied de novo through mutations? We know even less about what factors limit rates of adaptation. Answers to these questions are crucial for Evolutionary Biology, but also for believable quantifications of the evolutionary potential of populations. Population genetic theory makes predictions and allows inference from the patterns of polymorphism within species and divergence between species. Yet models specifying the fitness effects of mutations are often missing. Fitness landscape models will be mobilized to fill this gap and develop methods for inferring the distribution of fitness effects and factors governing rates of adaptation. Insights into the processes underlying adaptation will thus be gained from experimental evolution and population genomics data. The applicability of insights gained from experimental evolution to comprehend adaptation in nature will be scrutinized. We will unite two very different approaches for studying adaptation. The project will boost our understanding of how selection shapes genomes and open the way for further quantitative tests of theories of adaptation."
Max ERC Funding
1 159 857 €
Duration
Start date: 2013-04-01, End date: 2018-03-31
Project acronym AIDA
Project An Illumination of the Dark Ages: modeling reionization and interpreting observations
Researcher (PI) Andrei Albert Mesinger
Host Institution (HI) SCUOLA NORMALE SUPERIORE
Call Details Starting Grant (StG), PE9, ERC-2014-STG
Summary "Understanding the dawn of the first galaxies and how their light permeated the early Universe is at the very frontier of modern astrophysical cosmology. Generous resources, including ambitions observational programs, are being devoted to studying these epochs of Cosmic Dawn (CD) and Reionization (EoR). In order to interpret these observations, we propose to build on our widely-used, semi-numeric simulation tool, 21cmFAST, and apply it to observations. Using sub-grid, semi-analytic models, we will incorporate additional physical processes governing the evolution of sources and sinks of ionizing photons. The resulting state-of-the-art simulations will be well poised to interpret topical observations of quasar spectra and the cosmic 21cm signal. They would be both physically-motivated and fast, allowing us to rapidly explore astrophysical parameter space. We will statistically quantify the resulting degeneracies and constraints, providing a robust answer to the question, ""What can we learn from EoR/CD observations?"" As an end goal, these investigations will help us understand when the first generations of galaxies formed, how they drove the EoR, and what are the associated large-scale observational signatures."
Summary
"Understanding the dawn of the first galaxies and how their light permeated the early Universe is at the very frontier of modern astrophysical cosmology. Generous resources, including ambitions observational programs, are being devoted to studying these epochs of Cosmic Dawn (CD) and Reionization (EoR). In order to interpret these observations, we propose to build on our widely-used, semi-numeric simulation tool, 21cmFAST, and apply it to observations. Using sub-grid, semi-analytic models, we will incorporate additional physical processes governing the evolution of sources and sinks of ionizing photons. The resulting state-of-the-art simulations will be well poised to interpret topical observations of quasar spectra and the cosmic 21cm signal. They would be both physically-motivated and fast, allowing us to rapidly explore astrophysical parameter space. We will statistically quantify the resulting degeneracies and constraints, providing a robust answer to the question, ""What can we learn from EoR/CD observations?"" As an end goal, these investigations will help us understand when the first generations of galaxies formed, how they drove the EoR, and what are the associated large-scale observational signatures."
Max ERC Funding
1 468 750 €
Duration
Start date: 2015-05-01, End date: 2021-01-31
Project acronym ALLELECHOKER
Project DNA binding proteins for treatment of gain of function mutations
Researcher (PI) Enrico Maria Surace
Host Institution (HI) FONDAZIONE TELETHON
Call Details Starting Grant (StG), LS7, ERC-2012-StG_20111109
Summary Zinc finger (ZF) and transcription activator-like effector (TALE) based technologies are been allowing the tailored design of “artificial” DNA-binding proteins targeted to specific and unique DNA genomic sequences. Coupling DNA binding proteins to effectors domains enables the constitution of DNA binding factors for genomic directed transcriptional modulation or targeted genomic editing. We have demonstrated that pairing a ZF DNA binding protein to the transcriptional repressor Kruppel-associated box enables in vivo, the transcriptional repression of one of the most abundantly expressed gene in mammals, the human rhodopsin gene (RHO). We propose to generate RHO DNA binding silencers (“AlleleChoker”), which inactivate RHO either by transcriptional repression or targeted genome modification, irrespectively to wild-type or mutated alleles (mutational-independent approach), and combine RHO endogenous silencing to RHO replacement (silencing-replacement strategy). With this strategy in principle a single bimodal bio-therapeutic will enable the correction of any photoreceptor disease associated with RHO mutation. Adeno-associated viral (AAV) vector-based delivery will be used for photoreceptors gene transfer. Specifically our objectives are: 1) Construction of transcriptional repressors and nucleases for RHO silencing. Characterization and comparison of RHO silencing mediated by transcriptional repressors (ZFR/ TALER) or nucleases (ZFN/ TALEN) to generate genomic directed inactivation by non-homologous end-joining (NHEJ), and refer these results to RNA interference (RNAi) targeted to RHO; 2) RHO silencing in photoreceptors. to determine genome-wide DNA binding specificity of silencers, chromatin modifications and expression profile on human retinal explants; 3) Tuning silencing and replacement. To determine the impact of gene silencing-replacement strategy on disease progression in animal models of autosomal dominant retinitis pigmentosa (adRP) associated to RHO mutations
Summary
Zinc finger (ZF) and transcription activator-like effector (TALE) based technologies are been allowing the tailored design of “artificial” DNA-binding proteins targeted to specific and unique DNA genomic sequences. Coupling DNA binding proteins to effectors domains enables the constitution of DNA binding factors for genomic directed transcriptional modulation or targeted genomic editing. We have demonstrated that pairing a ZF DNA binding protein to the transcriptional repressor Kruppel-associated box enables in vivo, the transcriptional repression of one of the most abundantly expressed gene in mammals, the human rhodopsin gene (RHO). We propose to generate RHO DNA binding silencers (“AlleleChoker”), which inactivate RHO either by transcriptional repression or targeted genome modification, irrespectively to wild-type or mutated alleles (mutational-independent approach), and combine RHO endogenous silencing to RHO replacement (silencing-replacement strategy). With this strategy in principle a single bimodal bio-therapeutic will enable the correction of any photoreceptor disease associated with RHO mutation. Adeno-associated viral (AAV) vector-based delivery will be used for photoreceptors gene transfer. Specifically our objectives are: 1) Construction of transcriptional repressors and nucleases for RHO silencing. Characterization and comparison of RHO silencing mediated by transcriptional repressors (ZFR/ TALER) or nucleases (ZFN/ TALEN) to generate genomic directed inactivation by non-homologous end-joining (NHEJ), and refer these results to RNA interference (RNAi) targeted to RHO; 2) RHO silencing in photoreceptors. to determine genome-wide DNA binding specificity of silencers, chromatin modifications and expression profile on human retinal explants; 3) Tuning silencing and replacement. To determine the impact of gene silencing-replacement strategy on disease progression in animal models of autosomal dominant retinitis pigmentosa (adRP) associated to RHO mutations
Max ERC Funding
1 354 840 €
Duration
Start date: 2013-02-01, End date: 2018-01-31
Project acronym ANOREP
Project Targeting the reproductive biology of the malaria mosquito Anopheles gambiae: from laboratory studies to field applications
Researcher (PI) Flaminia Catteruccia
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PERUGIA
Call Details Starting Grant (StG), LS2, ERC-2010-StG_20091118
Summary Anopheles gambiae mosquitoes are the major vectors of malaria, a disease with devastating consequences for
human health. Novel methods for controlling the natural vector populations are urgently needed, given the
evolution of insecticide resistance in mosquitoes and the lack of novel insecticidals. Understanding the
processes at the bases of mosquito biology may help to roll back malaria. In this proposal, we will target
mosquito reproduction, a major determinant of the An. gambiae vectorial capacity. This will be achieved at
two levels: (i) fundamental research, to provide a deeper knowledge of the processes regulating reproduction
in this species, and (ii) applied research, to identify novel targets and to develop innovative approaches for
the control of natural populations. We will focus our analysis on three major players of mosquito
reproduction: male accessory glands (MAGs), sperm, and spermatheca, in both laboratory and field settings.
We will then translate this information into the identification of inhibitors of mosquito fertility. The
experimental activities will be divided across three objectives. In Objective 1, we will unravel the role of the
MAGs in shaping mosquito fertility and behaviour, by performing a combination of transcriptional and
functional studies that will reveal the multifaceted activities of these tissues. In Objective 2 we will instead
focus on the identification of the male and female factors responsible for sperm viability and function.
Results obtained in both objectives will be validated in field mosquitoes. In Objective 3, we will perform
screens aimed at the identification of inhibitors of mosquito reproductive success. This study will reveal as
yet unknown molecular mechanisms underlying reproductive success in mosquitoes, considerably increasing
our knowledge beyond the state-of-the-art and critically contributing with innovative tools and ideas to the
fight against malaria.
Summary
Anopheles gambiae mosquitoes are the major vectors of malaria, a disease with devastating consequences for
human health. Novel methods for controlling the natural vector populations are urgently needed, given the
evolution of insecticide resistance in mosquitoes and the lack of novel insecticidals. Understanding the
processes at the bases of mosquito biology may help to roll back malaria. In this proposal, we will target
mosquito reproduction, a major determinant of the An. gambiae vectorial capacity. This will be achieved at
two levels: (i) fundamental research, to provide a deeper knowledge of the processes regulating reproduction
in this species, and (ii) applied research, to identify novel targets and to develop innovative approaches for
the control of natural populations. We will focus our analysis on three major players of mosquito
reproduction: male accessory glands (MAGs), sperm, and spermatheca, in both laboratory and field settings.
We will then translate this information into the identification of inhibitors of mosquito fertility. The
experimental activities will be divided across three objectives. In Objective 1, we will unravel the role of the
MAGs in shaping mosquito fertility and behaviour, by performing a combination of transcriptional and
functional studies that will reveal the multifaceted activities of these tissues. In Objective 2 we will instead
focus on the identification of the male and female factors responsible for sperm viability and function.
Results obtained in both objectives will be validated in field mosquitoes. In Objective 3, we will perform
screens aimed at the identification of inhibitors of mosquito reproductive success. This study will reveal as
yet unknown molecular mechanisms underlying reproductive success in mosquitoes, considerably increasing
our knowledge beyond the state-of-the-art and critically contributing with innovative tools and ideas to the
fight against malaria.
Max ERC Funding
1 500 000 €
Duration
Start date: 2011-01-01, End date: 2015-12-31
Project acronym ANTS
Project Attine ANT SymbiomeS
Researcher (PI) Jacobus Jan Boomsma
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Advanced Grant (AdG), LS8, ERC-2012-ADG_20120314
Summary "The attine fungus-growing ants are prime models for understanding phenotypic adaptations in social evolution and symbiosis. The mutualism has many hallmarks of advanced cooperation in its mating system commitments and functional complementarity between multiple symbiont partners, but potential conflicts between sexes and castes over reproductive priorities, and between hosts and symbionts over symbiont mixing have also been documented. With collaborators at BGI-Shenzhen and the Smithsonian Institution my group has obtained six reference genomes representing all genus-level branches of the higher attine ants and a lower attine outgroup. With collaborators in Denmark and Australia we have pioneered proteomic approaches to understand the preservation of sperm viability in spite of sperm competition and the enzymatic decomposition of plant substrates that the ants use to make their fungus gardens grow.
Here, I propose an integrated study focusing on four major areas of attine ant biology that are particularly inviting for in depth molecular approaches: 1. The protein-level networks that secure life-time (up to 20 years) sperm storage in specialized ant-queen organs and the genetic mechanisms that shape and adjust these “sexual symbiome” networks. 2. The ant-fungal symbiome, i.e. the dynamics of fungal enzyme production for plant substrate degradation and the redistribution of these enzymes in fungus gardens through fecal deposition after they are ingested but not digested by the ants. 3. The microbial symbiome of ant guts and other tissues with obligate bacterial mutualists, of which we have identified some and will characterize a wider collection across the different branches of the attine ant phylogeny. 4. The genome-wide frequency of genomic imprinting and the significance of these imprints for the expression of caste phenotypes and the regulation of potential reproductive conflicts."
Summary
"The attine fungus-growing ants are prime models for understanding phenotypic adaptations in social evolution and symbiosis. The mutualism has many hallmarks of advanced cooperation in its mating system commitments and functional complementarity between multiple symbiont partners, but potential conflicts between sexes and castes over reproductive priorities, and between hosts and symbionts over symbiont mixing have also been documented. With collaborators at BGI-Shenzhen and the Smithsonian Institution my group has obtained six reference genomes representing all genus-level branches of the higher attine ants and a lower attine outgroup. With collaborators in Denmark and Australia we have pioneered proteomic approaches to understand the preservation of sperm viability in spite of sperm competition and the enzymatic decomposition of plant substrates that the ants use to make their fungus gardens grow.
Here, I propose an integrated study focusing on four major areas of attine ant biology that are particularly inviting for in depth molecular approaches: 1. The protein-level networks that secure life-time (up to 20 years) sperm storage in specialized ant-queen organs and the genetic mechanisms that shape and adjust these “sexual symbiome” networks. 2. The ant-fungal symbiome, i.e. the dynamics of fungal enzyme production for plant substrate degradation and the redistribution of these enzymes in fungus gardens through fecal deposition after they are ingested but not digested by the ants. 3. The microbial symbiome of ant guts and other tissues with obligate bacterial mutualists, of which we have identified some and will characterize a wider collection across the different branches of the attine ant phylogeny. 4. The genome-wide frequency of genomic imprinting and the significance of these imprints for the expression of caste phenotypes and the regulation of potential reproductive conflicts."
Max ERC Funding
2 290 102 €
Duration
Start date: 2013-05-01, End date: 2018-04-30
Project acronym ArtHep
Project Hepatocytes-Like Microreactors for Liver Tissue Engineering
Researcher (PI) Brigitte STADLER
Host Institution (HI) AARHUS UNIVERSITET
Call Details Consolidator Grant (CoG), LS9, ERC-2018-COG
Summary The global epidemics of obesity and diabetes type 2 lead to higher abundancy of medical conditions like non-alcoholic fatty liver disease causing an increase in liver failure and demand for liver transplants. The shortage of donor organs and the insufficient success in tissue engineering to ex vivo grow complex organs like the liver is a global medical challenge.
ArtHep targets the assembly of hepatic-like tissue, consisting of biological and synthetic entities, mimicking the core structure elements and key functions of the liver. ArtHep comprises an entirely new concept in liver regeneration with multi-angled core impact: i) cell mimics are expected to reduce the pressure to obtain donor cells, ii) the integrated biocatalytic subunits are destined to take over tasks of the damaged liver slowing down the progress of liver damage, and iii) the matching micro-environment in the bioprinted tissue is anticipated to facilitate the connection between the transplant and the liver.
Success criteria of ArtHep include engineering enzyme-mimics, which can perform core biocatalytic conversions similar to the liver, the assembly of biocatalytic active subunits and their encapsulation in cell-like carriers (microreactors), which have mechanical properties that match the liver tissue and that have a camouflaging coating to mimic the surface cues of liver tissue-relevant cells. Finally, matured bioprinted liver-lobules consisting of microreactors and live cells need to connect to liver tissue when transplanted into rats.
I am convinced that the ground-breaking research in ArtHep will contribute to the excellence of science in Europe while providing the game-changing foundation to counteract the ever increasing donor liver shortage. Further, consolidating my scientific efforts and moving them forward into unexplored dimensions in biomimicry for medical purposes, is a unique opportunity to advance my career.
Summary
The global epidemics of obesity and diabetes type 2 lead to higher abundancy of medical conditions like non-alcoholic fatty liver disease causing an increase in liver failure and demand for liver transplants. The shortage of donor organs and the insufficient success in tissue engineering to ex vivo grow complex organs like the liver is a global medical challenge.
ArtHep targets the assembly of hepatic-like tissue, consisting of biological and synthetic entities, mimicking the core structure elements and key functions of the liver. ArtHep comprises an entirely new concept in liver regeneration with multi-angled core impact: i) cell mimics are expected to reduce the pressure to obtain donor cells, ii) the integrated biocatalytic subunits are destined to take over tasks of the damaged liver slowing down the progress of liver damage, and iii) the matching micro-environment in the bioprinted tissue is anticipated to facilitate the connection between the transplant and the liver.
Success criteria of ArtHep include engineering enzyme-mimics, which can perform core biocatalytic conversions similar to the liver, the assembly of biocatalytic active subunits and their encapsulation in cell-like carriers (microreactors), which have mechanical properties that match the liver tissue and that have a camouflaging coating to mimic the surface cues of liver tissue-relevant cells. Finally, matured bioprinted liver-lobules consisting of microreactors and live cells need to connect to liver tissue when transplanted into rats.
I am convinced that the ground-breaking research in ArtHep will contribute to the excellence of science in Europe while providing the game-changing foundation to counteract the ever increasing donor liver shortage. Further, consolidating my scientific efforts and moving them forward into unexplored dimensions in biomimicry for medical purposes, is a unique opportunity to advance my career.
Max ERC Funding
1 992 289 €
Duration
Start date: 2019-05-01, End date: 2024-04-30
