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 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 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
Project acronym ASTERISK
Project ASTERoseismic Investigations with SONG and Kepler
Researcher (PI) Jørgen Christensen-Dalsgaard
Host Institution (HI) AARHUS UNIVERSITET
Call Details Advanced Grant (AdG), PE9, ERC-2010-AdG_20100224
Summary The project aims at a breakthrough in our understanding of stellar evolution, by combining advanced observations of stellar oscillations with state-of-the-art modelling of stars. This will largely be based on very extensive and precise data on stellar oscillations from the NASA Kepler mission launched in March 2009, but additional high-quality data will also be included. In particular, my group is developing the global SONG network for observations of stellar oscillations. These observational efforts will be supplemented by sophisticated modelling of stellar evolution, and by the development of asteroseismic tools to use the observations to probe stellar interiors. This will lead to a far more reliable determination of stellar ages, and hence ages of other astrophysical objects; it will compare the properties of the Sun with other stars and hence provide an understanding of the life history of the Sun; it will investigate the physical processes that control stellar properties, both at the level of the thermodynamical properties of stellar plasmas and the hydrodynamical instabilities that play a central role in stellar evolution; and it will characterize central stars in extra-solar planetary systems, determining the size and age of the star and hence constrain the evolution of the planetary systems. The Kepler data will be analysed in a large international collaboration coordinated by our group. The SONG network, which will become partially operational during the present project, will yield even detailed information about the conditions in the interior of stars, allowing tests of subtle but central aspects of the physics of stellar interiors. The projects involve the organization of a central data archive for asteroseismic data, at the Royal Library, Copenhagen.
Summary
The project aims at a breakthrough in our understanding of stellar evolution, by combining advanced observations of stellar oscillations with state-of-the-art modelling of stars. This will largely be based on very extensive and precise data on stellar oscillations from the NASA Kepler mission launched in March 2009, but additional high-quality data will also be included. In particular, my group is developing the global SONG network for observations of stellar oscillations. These observational efforts will be supplemented by sophisticated modelling of stellar evolution, and by the development of asteroseismic tools to use the observations to probe stellar interiors. This will lead to a far more reliable determination of stellar ages, and hence ages of other astrophysical objects; it will compare the properties of the Sun with other stars and hence provide an understanding of the life history of the Sun; it will investigate the physical processes that control stellar properties, both at the level of the thermodynamical properties of stellar plasmas and the hydrodynamical instabilities that play a central role in stellar evolution; and it will characterize central stars in extra-solar planetary systems, determining the size and age of the star and hence constrain the evolution of the planetary systems. The Kepler data will be analysed in a large international collaboration coordinated by our group. The SONG network, which will become partially operational during the present project, will yield even detailed information about the conditions in the interior of stars, allowing tests of subtle but central aspects of the physics of stellar interiors. The projects involve the organization of a central data archive for asteroseismic data, at the Royal Library, Copenhagen.
Max ERC Funding
2 498 149 €
Duration
Start date: 2011-04-01, End date: 2016-03-31
Project acronym BYPASSWITHOUTSURGERY
Project Reaching the effects of gastric bypass on diabetes and obesity without surgery
Researcher (PI) Jens Juul Holst
Host Institution (HI) KOBENHAVNS UNIVERSITET
Call Details Advanced Grant (AdG), LS4, ERC-2015-AdG
Summary Gastric bypass surgery results in massive weight loss and diabetes remission. The effect is superior to intensive medical treatment, showing that there are mechanisms within the body that can cure diabetes and obesity. Revealing the nature of these mechanisms could lead to new, cost-efficient, similarly effective, non-invasive treatments of these conditions. The hypothesis is that hyper-secretion of a number of gut hormones mediates the effect of surgery, as indicated by a series of our recent studies, demonstrating that hypersecretion of GLP-1, a hormone discovered in my laboratory and basis for the antidiabetic medication of millions of patients, is essential for the improved insulin secretion and glucose tolerance. But what are the mechanisms behind the up to 30-fold elevations in secretion of these hormones following surgery? Constantly with a translational scope, all elements involved in these responses will be addressed in this project, from detailed analysis of food items responsible for hormone secretion, to identification of the responsible regions of the gut, and to the molecular mechanisms leading to hypersecretion. Novel approaches for studies of human gut hormone secreting cells, including specific expression analysis, are combined with our advanced and unique isolated perfused gut preparations, the only tool that can provide physiologically relevant results with a translational potential regarding regulation of hormone secretion in the gut. This will lead to further groundbreaking experimental attempts to mimic and engage the identified mechanisms, creating similar hypersecretion and obtaining similar improvements as the operations in patients with obesity and diabetes. Based on our profound knowledge of gut hormone biology accumulated through decades of intensive and successful research and our successful elucidation of the antidiabetic actions of gastric bypass surgery, we are in a unique position to reach this ambitious goal.
Summary
Gastric bypass surgery results in massive weight loss and diabetes remission. The effect is superior to intensive medical treatment, showing that there are mechanisms within the body that can cure diabetes and obesity. Revealing the nature of these mechanisms could lead to new, cost-efficient, similarly effective, non-invasive treatments of these conditions. The hypothesis is that hyper-secretion of a number of gut hormones mediates the effect of surgery, as indicated by a series of our recent studies, demonstrating that hypersecretion of GLP-1, a hormone discovered in my laboratory and basis for the antidiabetic medication of millions of patients, is essential for the improved insulin secretion and glucose tolerance. But what are the mechanisms behind the up to 30-fold elevations in secretion of these hormones following surgery? Constantly with a translational scope, all elements involved in these responses will be addressed in this project, from detailed analysis of food items responsible for hormone secretion, to identification of the responsible regions of the gut, and to the molecular mechanisms leading to hypersecretion. Novel approaches for studies of human gut hormone secreting cells, including specific expression analysis, are combined with our advanced and unique isolated perfused gut preparations, the only tool that can provide physiologically relevant results with a translational potential regarding regulation of hormone secretion in the gut. This will lead to further groundbreaking experimental attempts to mimic and engage the identified mechanisms, creating similar hypersecretion and obtaining similar improvements as the operations in patients with obesity and diabetes. Based on our profound knowledge of gut hormone biology accumulated through decades of intensive and successful research and our successful elucidation of the antidiabetic actions of gastric bypass surgery, we are in a unique position to reach this ambitious goal.
Max ERC Funding
2 500 000 €
Duration
Start date: 2017-01-01, End date: 2021-12-31
Project acronym C-MORPH
Project Noninvasive cell specific morphometry in neuroinflammation and degeneration
Researcher (PI) Henrik LUNDELL
Host Institution (HI) REGION HOVEDSTADEN
Call Details Starting Grant (StG), LS7, ERC-2018-STG
Summary Brain structure determines function. Disentangling regional microstructural properties and understanding how these properties constitute brain function is a central goal of neuroimaging of the human brain and a key prerequisite for a mechanistic understanding of brain diseases and their treatment. Using magnetic resonance (MR) imaging, previous research has established links between regional brain microstructure and inter-individual variation in brain function, but this line of research has been limited by the non-specificity of MR-derived markers. This hampers the application of MR imaging as a tool to identify specific fingerprints of the underlying disease process.
Exploiting state-of-the-art ultra-high field MR imaging techniques, I have recently developed two independent spectroscopic MR methods that have the potential to tackle this challenge: Powder averaged diffusion weighted spectroscopy (PADWS) can provide an unbiased marker for cell specific structural degeneration, and Spectrally tuned gradient trajectories (STGT) can isolate cell shape and size. In this project, I will harness these innovations for MR-based precision medicine. I will advance PADWS and STGT methodology on state-of-the-art MR hardware and harvest the synergy of these methods to realize Cell-specific in-vivo MORPHOMETRY (C-MORPH) of the intact human brain. I will establish novel MR read-outs and analyses to derive cell-type specific tissue properties in the healthy and diseased brain and validate them with the help of a strong translational experimental framework, including histological validation. Once validated, the experimental methods and analyses will be simplified and adapted to provide clinically applicable tools. This will push the frontiers of MR-based personalized medicine, guiding therapeutic decisions by providing sensitive probes of cell-specific microstructural changes caused by inflammation, neurodegeneration or treatment response.
Summary
Brain structure determines function. Disentangling regional microstructural properties and understanding how these properties constitute brain function is a central goal of neuroimaging of the human brain and a key prerequisite for a mechanistic understanding of brain diseases and their treatment. Using magnetic resonance (MR) imaging, previous research has established links between regional brain microstructure and inter-individual variation in brain function, but this line of research has been limited by the non-specificity of MR-derived markers. This hampers the application of MR imaging as a tool to identify specific fingerprints of the underlying disease process.
Exploiting state-of-the-art ultra-high field MR imaging techniques, I have recently developed two independent spectroscopic MR methods that have the potential to tackle this challenge: Powder averaged diffusion weighted spectroscopy (PADWS) can provide an unbiased marker for cell specific structural degeneration, and Spectrally tuned gradient trajectories (STGT) can isolate cell shape and size. In this project, I will harness these innovations for MR-based precision medicine. I will advance PADWS and STGT methodology on state-of-the-art MR hardware and harvest the synergy of these methods to realize Cell-specific in-vivo MORPHOMETRY (C-MORPH) of the intact human brain. I will establish novel MR read-outs and analyses to derive cell-type specific tissue properties in the healthy and diseased brain and validate them with the help of a strong translational experimental framework, including histological validation. Once validated, the experimental methods and analyses will be simplified and adapted to provide clinically applicable tools. This will push the frontiers of MR-based personalized medicine, guiding therapeutic decisions by providing sensitive probes of cell-specific microstructural changes caused by inflammation, neurodegeneration or treatment response.
Max ERC Funding
1 498 811 €
Duration
Start date: 2018-12-01, End date: 2023-11-30
Project acronym CASINO
Project Carbohydrate signals controlling nodulation
Researcher (PI) Jens Stougaard Jensen
Host Institution (HI) AARHUS UNIVERSITET
Call Details Advanced Grant (AdG), LS3, ERC-2010-AdG_20100317
Summary Mechanisms governing interaction between multicellular organisms and microbes are central for understanding pathogenesis, symbiosis and the function of ecosystems. We propose to address these mechanisms by pioneering an interdisciplinary approach for understanding cellular signalling, response processes and organ development. The challenge is to determine factors synchronising three processes, organogenesis, infection thread formation and bacterial infection, running in parallel to build a root nodule hosting symbiotic bacteria. We aim to exploit the unique possibilities for analysing endocytosis of bacteria in model legumes and to develop genomic, genetic and biological chemistry tools to break new ground in our understanding of carbohydrates in plant development and plant-microbe interaction. Surface exposed rhizobial polysaccharides play a crucial but poorly understood role in infection thread formation and rhizobial invasion resulting in endocytosis. We will undertake an integrated functional characterisation of receptor-ligand mechanisms mediating recognition of secreted polysaccharides and subsequent signal amplification. So far progress in this field has been limited by the complex nature of carbohydrate polymers, lack of a suitable experimental model system where both partners in an interaction could be manipulated and lack of corresponding methods for carbohydrate synthesis, analysis and interaction studies. In this context our legume model system and the discovery that the legume Nod-factor receptors recognise bacterial lipochitin-oligosaccharide signals at their LysM domains provides a new opportunity. Combined with advanced bioorganic chemistry and nanobioscience approaches this proposal will engage the above mentioned limitations.
Summary
Mechanisms governing interaction between multicellular organisms and microbes are central for understanding pathogenesis, symbiosis and the function of ecosystems. We propose to address these mechanisms by pioneering an interdisciplinary approach for understanding cellular signalling, response processes and organ development. The challenge is to determine factors synchronising three processes, organogenesis, infection thread formation and bacterial infection, running in parallel to build a root nodule hosting symbiotic bacteria. We aim to exploit the unique possibilities for analysing endocytosis of bacteria in model legumes and to develop genomic, genetic and biological chemistry tools to break new ground in our understanding of carbohydrates in plant development and plant-microbe interaction. Surface exposed rhizobial polysaccharides play a crucial but poorly understood role in infection thread formation and rhizobial invasion resulting in endocytosis. We will undertake an integrated functional characterisation of receptor-ligand mechanisms mediating recognition of secreted polysaccharides and subsequent signal amplification. So far progress in this field has been limited by the complex nature of carbohydrate polymers, lack of a suitable experimental model system where both partners in an interaction could be manipulated and lack of corresponding methods for carbohydrate synthesis, analysis and interaction studies. In this context our legume model system and the discovery that the legume Nod-factor receptors recognise bacterial lipochitin-oligosaccharide signals at their LysM domains provides a new opportunity. Combined with advanced bioorganic chemistry and nanobioscience approaches this proposal will engage the above mentioned limitations.
Max ERC Funding
2 399 127 €
Duration
Start date: 2011-05-01, End date: 2016-04-30
