Project acronym EcoLipid
Project Ecophysiology of membrane lipid remodelling in marine bacteria
Researcher (PI) Yin CHEN
Host Institution (HI) THE UNIVERSITY OF WARWICK
Call Details Consolidator Grant (CoG), LS8, ERC-2016-COG
Summary "Membrane lipids form the structural basis of all cells. In bacteria Escherichia coli uses predominantly phosphorus-containing lipids (phospholipids) in its cell envelope, including phosphatidylethanolamine and phosphatidylglycerol. However, beyond E. coli a range of lipids are found in bacterial membranes, including phospholipids as well as phosphorus (P)-free lipids such as betaine lipids, ornithine lipids, sulfolipids and glycolipids. In the marine environment, it is well established that P availability significantly affects lipid composition in the phytoplankton, whereby non-P sulfur-containing lipids are used to substitute phospholipids in response to P stress. This remodeling offers a significant competitive advantage for these organisms, allowing them to adapt to oligotrophic environments low in P. Until very recently, abundant marine heterotrophic bacteria were thought to lack the capacity for lipid remodelling in response to P deficiency. However, recent work by myself and others has now demonstrated that lipid remodelling occurs in many ecologically important marine heterotrophs, such as the SAR11 and Roseobacter clades, which are not only numerically abundant in marine waters but also crucial players in the biogeochemical cycling of key elements. However, the ecological and physiological consequences of lipid remodeling, in response to nutrient limitation, remain unknown. This is important because I hypothesize that lipid remodeling has important knock-on effects restricting the ability of marine bacteria to deal with both abiotic and biotic stresses, which has profound consequences for the functioning of major biogeochemical cycles. Here I aim to use a synthesis of molecular biology, microbial physiology, and "omics" approaches to reveal the fitness trade-offs of lipid remodelling in cosmopolitan marine heterotrophic bacteria, providing novel insights into the ecophysiology of lipid remodelling and its consequences for marine nutrient cycling."
Summary
"Membrane lipids form the structural basis of all cells. In bacteria Escherichia coli uses predominantly phosphorus-containing lipids (phospholipids) in its cell envelope, including phosphatidylethanolamine and phosphatidylglycerol. However, beyond E. coli a range of lipids are found in bacterial membranes, including phospholipids as well as phosphorus (P)-free lipids such as betaine lipids, ornithine lipids, sulfolipids and glycolipids. In the marine environment, it is well established that P availability significantly affects lipid composition in the phytoplankton, whereby non-P sulfur-containing lipids are used to substitute phospholipids in response to P stress. This remodeling offers a significant competitive advantage for these organisms, allowing them to adapt to oligotrophic environments low in P. Until very recently, abundant marine heterotrophic bacteria were thought to lack the capacity for lipid remodelling in response to P deficiency. However, recent work by myself and others has now demonstrated that lipid remodelling occurs in many ecologically important marine heterotrophs, such as the SAR11 and Roseobacter clades, which are not only numerically abundant in marine waters but also crucial players in the biogeochemical cycling of key elements. However, the ecological and physiological consequences of lipid remodeling, in response to nutrient limitation, remain unknown. This is important because I hypothesize that lipid remodeling has important knock-on effects restricting the ability of marine bacteria to deal with both abiotic and biotic stresses, which has profound consequences for the functioning of major biogeochemical cycles. Here I aim to use a synthesis of molecular biology, microbial physiology, and "omics" approaches to reveal the fitness trade-offs of lipid remodelling in cosmopolitan marine heterotrophic bacteria, providing novel insights into the ecophysiology of lipid remodelling and its consequences for marine nutrient cycling."
Max ERC Funding
1 965 114 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym EPGR
Project The Evolution Problem in General Relativity
Researcher (PI) Jérémie Szeftel
Host Institution (HI) SORBONNE UNIVERSITE
Call Details Consolidator Grant (CoG), PE1, ERC-2016-COG
Summary General relativity has been introduced by A. Einstein in 1915. It is a major theory of modern physics and at the same time has led to fascinating mathematical problems. The present proposal focusses on two aspects of the evolution problem for the Einstein equations which has been initiated by the pioneering work of Y. Choquet-Bruhat in 1952.
The Einstein equations form a nonlinear system of partial differential equations of hyperbolic type whose complexity raises significant challenges to its mathematical analysis. The goal of this project is to strengthen our understanding of two important themes concerning the evolution problem in general relativity. On the one hand, the control of low regularity solutions of the Einstein equations, a topic which is intimately linked with the celebrated cosmic censorship conjectures of R. Penrose, a major open problem in the field. On the other hand, the question of the stability of particular solutions of the Einstein equations in the wake of the groundbreaking proof of the stability of the Minkowski space-time due to D. Christodoulou and S. Klainerman. These directions are extremely active and have recently led to impressive results. More specifically, this project proposes to consider the following two work packages
-Going beyond the bounded L2 curvature theorem. This result has been recently obtained by the PI in collaboration with S. Klainerman and I. Rodnianski and is the sharpest result in so far as low regularity solutions of the Einstein equations are concerned. Yet, the fundamental quest towards a scale invariant well-posedness criterion for the Einstein equations remains wide open.
-The black hole stability problem. This problem concerns the stability of the Kerr metrics which form a 2-parameter family of solutions to the Einstein vacuum equations. Many results have been obtained concerning various versions of linear stability, but significant challenges remain in order to tackle the nonlinear stability result.
Summary
General relativity has been introduced by A. Einstein in 1915. It is a major theory of modern physics and at the same time has led to fascinating mathematical problems. The present proposal focusses on two aspects of the evolution problem for the Einstein equations which has been initiated by the pioneering work of Y. Choquet-Bruhat in 1952.
The Einstein equations form a nonlinear system of partial differential equations of hyperbolic type whose complexity raises significant challenges to its mathematical analysis. The goal of this project is to strengthen our understanding of two important themes concerning the evolution problem in general relativity. On the one hand, the control of low regularity solutions of the Einstein equations, a topic which is intimately linked with the celebrated cosmic censorship conjectures of R. Penrose, a major open problem in the field. On the other hand, the question of the stability of particular solutions of the Einstein equations in the wake of the groundbreaking proof of the stability of the Minkowski space-time due to D. Christodoulou and S. Klainerman. These directions are extremely active and have recently led to impressive results. More specifically, this project proposes to consider the following two work packages
-Going beyond the bounded L2 curvature theorem. This result has been recently obtained by the PI in collaboration with S. Klainerman and I. Rodnianski and is the sharpest result in so far as low regularity solutions of the Einstein equations are concerned. Yet, the fundamental quest towards a scale invariant well-posedness criterion for the Einstein equations remains wide open.
-The black hole stability problem. This problem concerns the stability of the Kerr metrics which form a 2-parameter family of solutions to the Einstein vacuum equations. Many results have been obtained concerning various versions of linear stability, but significant challenges remain in order to tackle the nonlinear stability result.
Max ERC Funding
1 455 000 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym FATE
Project Functional Biology of Hepatic CD8+ T cells
Researcher (PI) Matteo Iannacone
Host Institution (HI) OSPEDALE SAN RAFFAELE SRL
Call Details Consolidator Grant (CoG), LS6, ERC-2016-COG
Summary CD8+ T cells have a key role in eliminating intracellular pathogens and tumors that affect the liver. The protective capacity of these cells relies on their ability to migrate to and traffic within the liver, recognize pathogen- or tumor-derived antigens, get activated and deploy effector functions. While some of the rules that characterize CD8+ T cell behavior in the infected and cancerous liver have been characterized at the population level, we have only limited knowledge of the precise dynamics of intrahepatic CD8+ T cell conduct at the single-cell level. In preliminary data for this project we have developed several advanced imaging techniques that allow us to dissect the interactive behavior of CD8+ T cells within the mouse liver at an unprecedented level of spatial and temporal resolution. We predict that this approach, combined with unique models of hepatitis B virus pathogenesis and a new model of hepatocellular carcinoma created ad hoc for this proposal, will generate novel mechanistic insights into the spatiotemporal determinants that govern the capacity of CD8+ T cells to home and function in the virus- or tumor-bearing liver. Specifically, we plan to pursue two main goals: 1) To assess how the anatomical, hemodynamic and environmental cues that characterize hepatocellular carcinomas shape CD8+ T cell behavior and function; 2) To characterize intrahepatic T cell priming events that induce functionally defective T cell responses. Results emerging from these studies will advance our knowledge on how adaptive immunity mediates pathogen clearance and tumor elimination. This new knowledge may lead to improved vaccination and treatment strategies for immunotherapy of infectious diseases and cancer.
Summary
CD8+ T cells have a key role in eliminating intracellular pathogens and tumors that affect the liver. The protective capacity of these cells relies on their ability to migrate to and traffic within the liver, recognize pathogen- or tumor-derived antigens, get activated and deploy effector functions. While some of the rules that characterize CD8+ T cell behavior in the infected and cancerous liver have been characterized at the population level, we have only limited knowledge of the precise dynamics of intrahepatic CD8+ T cell conduct at the single-cell level. In preliminary data for this project we have developed several advanced imaging techniques that allow us to dissect the interactive behavior of CD8+ T cells within the mouse liver at an unprecedented level of spatial and temporal resolution. We predict that this approach, combined with unique models of hepatitis B virus pathogenesis and a new model of hepatocellular carcinoma created ad hoc for this proposal, will generate novel mechanistic insights into the spatiotemporal determinants that govern the capacity of CD8+ T cells to home and function in the virus- or tumor-bearing liver. Specifically, we plan to pursue two main goals: 1) To assess how the anatomical, hemodynamic and environmental cues that characterize hepatocellular carcinomas shape CD8+ T cell behavior and function; 2) To characterize intrahepatic T cell priming events that induce functionally defective T cell responses. Results emerging from these studies will advance our knowledge on how adaptive immunity mediates pathogen clearance and tumor elimination. This new knowledge may lead to improved vaccination and treatment strategies for immunotherapy of infectious diseases and cancer.
Max ERC Funding
2 390 000 €
Duration
Start date: 2017-07-01, End date: 2022-06-30
Project acronym FRAGCLIM
Project The Combined Effects of Climatic Warming and Habitat Fragmentation on Biodiversity, Community Dynamics and Ecosystem Functioning
Researcher (PI) Jose Maria MONTOYA TERAN
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), LS8, ERC-2016-COG
Summary Climatic warming and habitat fragmentation are the largest threats to biodiversity and ecosystems globally. To forecast and mitigate their effects is the environmental challenge of our age. Despite substantial progress on the ecological consequences of climatic warming and habitat fragmentation individually, there is a fundamental gap in our understanding and prediction of their combined effects.
The goal of FRAGCLIM is to determine the individual and combined effects of climatic warming and habitat fragmentation on biodiversity, community dynamics, and ecosystem functioning in complex multitrophic communities. To achieve this, it uses an integrative approach that combines the development of new theory on metacommunities and temperature-dependent food web dynamics in close dialogue with a unique long-term aquatic mesocosm experiment. It is articulated around five objectives. In the first three, FRAGCLIM will determine the effects of (i) warming, (ii) fragmentation, and (iii) warming and fragmentation combined, on numerous facets of biodiversity, community structure, food web dynamics, spatial and temporal stability, and key ecosystem functions. Then, it will (iv) investigate the extent of evolutionary thermal adaptation to warming and isolation due to fragmentation, and its consequences for biodiversity dynamics. Finally, (v) it will provide creative solutions to mitigate the combined effects of warming and fragmentation.
FRAGCLIM proposes an ambitious integrative and innovative research programme that will provide a much-needed new perspective on the ecological and evolutionary consequences of warming and fragmentation. It will greatly contribute to bridging the gaps between theoretical and empirical ecology, and between ecological and evolutionary responses to global change. FRAGCLIM will foster links with environmental policy by providing new mitigation measures to climate change in fragmented systems that derive from our theoretical and empirical findings.
Summary
Climatic warming and habitat fragmentation are the largest threats to biodiversity and ecosystems globally. To forecast and mitigate their effects is the environmental challenge of our age. Despite substantial progress on the ecological consequences of climatic warming and habitat fragmentation individually, there is a fundamental gap in our understanding and prediction of their combined effects.
The goal of FRAGCLIM is to determine the individual and combined effects of climatic warming and habitat fragmentation on biodiversity, community dynamics, and ecosystem functioning in complex multitrophic communities. To achieve this, it uses an integrative approach that combines the development of new theory on metacommunities and temperature-dependent food web dynamics in close dialogue with a unique long-term aquatic mesocosm experiment. It is articulated around five objectives. In the first three, FRAGCLIM will determine the effects of (i) warming, (ii) fragmentation, and (iii) warming and fragmentation combined, on numerous facets of biodiversity, community structure, food web dynamics, spatial and temporal stability, and key ecosystem functions. Then, it will (iv) investigate the extent of evolutionary thermal adaptation to warming and isolation due to fragmentation, and its consequences for biodiversity dynamics. Finally, (v) it will provide creative solutions to mitigate the combined effects of warming and fragmentation.
FRAGCLIM proposes an ambitious integrative and innovative research programme that will provide a much-needed new perspective on the ecological and evolutionary consequences of warming and fragmentation. It will greatly contribute to bridging the gaps between theoretical and empirical ecology, and between ecological and evolutionary responses to global change. FRAGCLIM will foster links with environmental policy by providing new mitigation measures to climate change in fragmented systems that derive from our theoretical and empirical findings.
Max ERC Funding
1 998 802 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
Project acronym GALOP
Project Galois theory of periods and applications.
Researcher (PI) Francis Clément Sais BROWN
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Consolidator Grant (CoG), PE1, ERC-2016-COG
Summary A period is a complex number defined by the integral of an algebraic differential form over a region defined by polynomial inequalities. Examples include: algebraic numbers, elliptic integrals, and Feynman integrals in high-energy physics. Many problems in mathematics can be cast as a statement involving periods. A deep idea, based on Grothendieck's philosophy of motives, is that there should be a Galois theory of periods, generalising classical Galois theory for algebraic numbers. This reposes on inaccessible conjectures in transcendence theory, but these can be circumvented in many important cases using an elementary notion of motivic periods. This allows one to set up a working Galois theory of periods in many situations of arithmetic and physical interest.
These ideas grew out of the PI's recent proof of the Deligne-Ihara conjecture, in which the Galois theory of multiple zeta values was worked out. Multiple zeta values are one of the most fundamental families of periods, and their Galois group plays an important role in mathematics: it is conjecturally equal to Drinfeld's Grothendieck-Teichmuller group, the stable derivation algebra on moduli spaces of curves, and the Galois group of mixed Tate motives over the integers. It occurs in deformation quantization, the homology of the graph complex, and the Kashiwara-Vergne problem, as well as having numerous connections to string theory, and quantum field theory.
The goal of this proposal is to generalise this picture. Periods of moduli spaces of curves, multiple L-functions of modular forms, and Feynman amplitudes in quantum field and string theory should each have their own Galois theory which is yet to be worked out.
This is completely uncharted territory, and will have numerous applications to number theory, algebraic geometry and physics.
Summary
A period is a complex number defined by the integral of an algebraic differential form over a region defined by polynomial inequalities. Examples include: algebraic numbers, elliptic integrals, and Feynman integrals in high-energy physics. Many problems in mathematics can be cast as a statement involving periods. A deep idea, based on Grothendieck's philosophy of motives, is that there should be a Galois theory of periods, generalising classical Galois theory for algebraic numbers. This reposes on inaccessible conjectures in transcendence theory, but these can be circumvented in many important cases using an elementary notion of motivic periods. This allows one to set up a working Galois theory of periods in many situations of arithmetic and physical interest.
These ideas grew out of the PI's recent proof of the Deligne-Ihara conjecture, in which the Galois theory of multiple zeta values was worked out. Multiple zeta values are one of the most fundamental families of periods, and their Galois group plays an important role in mathematics: it is conjecturally equal to Drinfeld's Grothendieck-Teichmuller group, the stable derivation algebra on moduli spaces of curves, and the Galois group of mixed Tate motives over the integers. It occurs in deformation quantization, the homology of the graph complex, and the Kashiwara-Vergne problem, as well as having numerous connections to string theory, and quantum field theory.
The goal of this proposal is to generalise this picture. Periods of moduli spaces of curves, multiple L-functions of modular forms, and Feynman amplitudes in quantum field and string theory should each have their own Galois theory which is yet to be worked out.
This is completely uncharted territory, and will have numerous applications to number theory, algebraic geometry and physics.
Max ERC Funding
1 997 959 €
Duration
Start date: 2017-03-01, End date: 2022-02-28
Project acronym GermlineAgeingSoma
Project Getting to the root of ageing: somatic decay as a cost of germline maintenance
Researcher (PI) Alexei MAKLAKOV
Host Institution (HI) UNIVERSITY OF EAST ANGLIA
Call Details Consolidator Grant (CoG), LS8, ERC-2016-COG
Summary The trade-off between survival and reproduction lies at the core of the evolutionary theory of ageing. Removal of germ cells extends somatic lifespan implying that reduced reproduction frees up resources for survival. Remarkably, however, the disruption of germline signalling increases lifespan without the obligatory reduction in fecundity, thus challenging the key role of the survival-reproduction trade-off. Recent breakthroughs suggest that protection and repair of the genome and the proteome of the germ cells is costly and compromised germline maintenance increases mutation rate, which can reduce offspring fitness. Thus, expensive germline maintenance can be a missing link in the puzzle of cost-free lifespan extension. This hypothesis predicts that when germline signalling is manipulated to increase investment into somatic cells, the germline maintenance will suffer resulting in increased mutation rate and reduced offspring fitness, even if total fecundity is unaffected. I propose a research program at the interface of evolutionary biology and biogerontology that focuses on phenotypic and evolutionary costs of germline maintenance. First, I will genetically manipulate germline signalling to boost investment into soma and estimate mutation rate and competitive fitness of the resulting offspring using Caenorhabditis elegans nematodes. Second, I will employ experimental evolution in nematodes to assess the long-term evolutionary costs of increased germline maintenance. Third, I will use germline transplantation in zebrafish Dario rerio to directly test whether germline proliferation reduces investment into soma in a vertebrate. Understanding how increased investment into the soma damages the germline and reduces offspring fitness will provide a major advance in our understanding of ageing evolution and will have serious implications for applied research programs aimed at harnessing the power of germline signalling to postpone ageing.
Summary
The trade-off between survival and reproduction lies at the core of the evolutionary theory of ageing. Removal of germ cells extends somatic lifespan implying that reduced reproduction frees up resources for survival. Remarkably, however, the disruption of germline signalling increases lifespan without the obligatory reduction in fecundity, thus challenging the key role of the survival-reproduction trade-off. Recent breakthroughs suggest that protection and repair of the genome and the proteome of the germ cells is costly and compromised germline maintenance increases mutation rate, which can reduce offspring fitness. Thus, expensive germline maintenance can be a missing link in the puzzle of cost-free lifespan extension. This hypothesis predicts that when germline signalling is manipulated to increase investment into somatic cells, the germline maintenance will suffer resulting in increased mutation rate and reduced offspring fitness, even if total fecundity is unaffected. I propose a research program at the interface of evolutionary biology and biogerontology that focuses on phenotypic and evolutionary costs of germline maintenance. First, I will genetically manipulate germline signalling to boost investment into soma and estimate mutation rate and competitive fitness of the resulting offspring using Caenorhabditis elegans nematodes. Second, I will employ experimental evolution in nematodes to assess the long-term evolutionary costs of increased germline maintenance. Third, I will use germline transplantation in zebrafish Dario rerio to directly test whether germline proliferation reduces investment into soma in a vertebrate. Understanding how increased investment into the soma damages the germline and reduces offspring fitness will provide a major advance in our understanding of ageing evolution and will have serious implications for applied research programs aimed at harnessing the power of germline signalling to postpone ageing.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym GRADIENTSENSING
Project Cellular navigation along spatial gradients
Researcher (PI) Michael Karl Sixt
Host Institution (HI) INSTITUTE OF SCIENCE AND TECHNOLOGYAUSTRIA
Call Details Consolidator Grant (CoG), LS3, ERC-2016-COG
Summary Gradients of extracellular signalling molecules are a central concept in biology: for example gradients of guidance-cues such as chemokines position migrating cells in development, malignancy and immunity. Because immune cells are permanently motile, their function most critically depends on spatiotemporal orchestration by a large family of chemokines. To specify direction, concentration differences of the chemokine need to be interpreted by the migrating cell. Most mechanistic knowledge about eukaryotic gradient sensing is inferred from the amoeba Dictyostelium discoideum migrating towards soluble gradients of cyclicAMP. The biology of chemokines is much more diverse, e.g. gradients can take different shapes and, importantly, they do not only emerge in the soluble but also in the immobilized phase. In this proposal we suggest to address the principles of leukocyte chemotaxis using convergent system wide, cell biological and intravital approaches. Employing a newly developed, genetically tractable primary leukocyte system, we will test the contribution of spatial and temporal signalling paradigms of gradient sensing. Quantitative microscopy will be used to image cellular responses to engineered immobilized and soluble chemokine gradients of defined shape as well as to optogenetically triggered signals. In a complementary approach we will screen for proteins responding to chemokine signalling and perform the first genome wide genome editing-based loss of function screen for directionally persistent chemotaxis and haptotaxis. Findings will be validated in vivo to guarantee physiological relevance. In a support project we will precision-engineer the genome of primary leukocytes suitable for assaying migration. A unique combination of cellular, genetic, engineering and quantitative microscopy tools will allow this new and holistic approach to a question which is not only fundamental for immunology but also for understanding development and cancer biology.
Summary
Gradients of extracellular signalling molecules are a central concept in biology: for example gradients of guidance-cues such as chemokines position migrating cells in development, malignancy and immunity. Because immune cells are permanently motile, their function most critically depends on spatiotemporal orchestration by a large family of chemokines. To specify direction, concentration differences of the chemokine need to be interpreted by the migrating cell. Most mechanistic knowledge about eukaryotic gradient sensing is inferred from the amoeba Dictyostelium discoideum migrating towards soluble gradients of cyclicAMP. The biology of chemokines is much more diverse, e.g. gradients can take different shapes and, importantly, they do not only emerge in the soluble but also in the immobilized phase. In this proposal we suggest to address the principles of leukocyte chemotaxis using convergent system wide, cell biological and intravital approaches. Employing a newly developed, genetically tractable primary leukocyte system, we will test the contribution of spatial and temporal signalling paradigms of gradient sensing. Quantitative microscopy will be used to image cellular responses to engineered immobilized and soluble chemokine gradients of defined shape as well as to optogenetically triggered signals. In a complementary approach we will screen for proteins responding to chemokine signalling and perform the first genome wide genome editing-based loss of function screen for directionally persistent chemotaxis and haptotaxis. Findings will be validated in vivo to guarantee physiological relevance. In a support project we will precision-engineer the genome of primary leukocytes suitable for assaying migration. A unique combination of cellular, genetic, engineering and quantitative microscopy tools will allow this new and holistic approach to a question which is not only fundamental for immunology but also for understanding development and cancer biology.
Max ERC Funding
1 984 922 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym GroIsRan
Project Growth, Isoperimetry and Random walks on Groups
Researcher (PI) ANNA ERSHLER
Host Institution (HI) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Call Details Consolidator Grant (CoG), PE1, ERC-2016-COG
Summary The goal of the project is to develop new techniques for estimation and evaluation of well-known asymptotic invariants of groups, including growth of groups, isoperimetric profiles, entropy and probability to return to the origin of random walks as well as of some more recent invariants related to the geometric criteria for construction of quotients of groups, which appeared in the joint work of PI with A.Karlsson (2010), and in a recent work of Ozawa (2015) giving a short functional analytic proof of the Polynomial Growth Theorem. We plan to work on the Gap conjecture of Grigorchuk, which states that any group of growth asymptotically strictly less than exp(n1/2) has polynomial growth, the question about the forms of Foelner sets in groups of intermediate and exponential growth and Kaimanovich and Vershik conjecture about characterisation of groups of exponential growth in terms of non-triviality of the Poisson boundary of some symmetric random walks. We plan to develop methods sharpening previous results of PI about isoperimetric inequalities for wreath products and relation between growth of groups and isoperimetry, and apply them for growth estimates and the description of the boundary.
A further goal of the project is to introduce new constructions of non-elementary amenable groups which can show that necessary conditions in growth conjecture and isoperimetric inequalities cannot be weakened.
Summary
The goal of the project is to develop new techniques for estimation and evaluation of well-known asymptotic invariants of groups, including growth of groups, isoperimetric profiles, entropy and probability to return to the origin of random walks as well as of some more recent invariants related to the geometric criteria for construction of quotients of groups, which appeared in the joint work of PI with A.Karlsson (2010), and in a recent work of Ozawa (2015) giving a short functional analytic proof of the Polynomial Growth Theorem. We plan to work on the Gap conjecture of Grigorchuk, which states that any group of growth asymptotically strictly less than exp(n1/2) has polynomial growth, the question about the forms of Foelner sets in groups of intermediate and exponential growth and Kaimanovich and Vershik conjecture about characterisation of groups of exponential growth in terms of non-triviality of the Poisson boundary of some symmetric random walks. We plan to develop methods sharpening previous results of PI about isoperimetric inequalities for wreath products and relation between growth of groups and isoperimetry, and apply them for growth estimates and the description of the boundary.
A further goal of the project is to introduce new constructions of non-elementary amenable groups which can show that necessary conditions in growth conjecture and isoperimetric inequalities cannot be weakened.
Max ERC Funding
1 789 438 €
Duration
Start date: 2017-09-01, End date: 2022-08-31
Project acronym HERPES
Project Herpesvirus Effectors of RNA synthesis, Processing, Export and Stability
Researcher (PI) Lars DÖLKEN
Host Institution (HI) JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG
Call Details Consolidator Grant (CoG), LS6, ERC-2016-COG
Summary Herpes simplex virus 1 (HSV-1) is an important human pathogen, which intensively interacts with the cellular transcriptional machinery at multiple levels during lytic infection. Employing next-generation sequencing to study RNA synthesis, processing and translation in short intervals throughout lytic HSV-1 infection, my laboratory made the surprising observation that HSV-1 triggers widespread disruption of transcription termination of cellular but not viral genes. Transcription commonly extends for tens-of-thousands of nucleotides beyond poly(A)-sites and into downstream genes. In contrast to textbook knowledge, HSV-1 infection does not inhibit splicing but induces a broad range of aberrant splicing events associated with disruption of transcription termination. Exploring these fascinating phenomena will provide fundamental insights into RNA biology of human cells.
The proposed work combines both hypothesis-driven and innovative unbiased screening approaches. I will utilise cutting-edge methodology ranging from high-throughput studies to advanced single molecule imaging. Thereby, I will detail the molecular mechanisms responsible for disruption of transcription termination and aberrant splicing. I will identify novel cellular proteins governing transcription termination using a genome-wide Cas9-knockout screen. I will develop RNA aptamer technology to visualise and track single RNA molecules suffering from poly(A) read-through. I will elucidate why transcription termination of some cellular and all viral genes remains unaltered throughout infection. I hypothesize that the alterations in RNA processing are depicted by specific changes in RNA Polymerase II CTD phosphorylation and in the associated proteins. I will characterise these dynamic changes using mNET-seq and quantitative proteomics. Finally, data-driven quantitative bioinformatic modelling will detail how the coupling of RNA synthesis, processing, export, stability and translation is orchestrated by HSV-1.
Summary
Herpes simplex virus 1 (HSV-1) is an important human pathogen, which intensively interacts with the cellular transcriptional machinery at multiple levels during lytic infection. Employing next-generation sequencing to study RNA synthesis, processing and translation in short intervals throughout lytic HSV-1 infection, my laboratory made the surprising observation that HSV-1 triggers widespread disruption of transcription termination of cellular but not viral genes. Transcription commonly extends for tens-of-thousands of nucleotides beyond poly(A)-sites and into downstream genes. In contrast to textbook knowledge, HSV-1 infection does not inhibit splicing but induces a broad range of aberrant splicing events associated with disruption of transcription termination. Exploring these fascinating phenomena will provide fundamental insights into RNA biology of human cells.
The proposed work combines both hypothesis-driven and innovative unbiased screening approaches. I will utilise cutting-edge methodology ranging from high-throughput studies to advanced single molecule imaging. Thereby, I will detail the molecular mechanisms responsible for disruption of transcription termination and aberrant splicing. I will identify novel cellular proteins governing transcription termination using a genome-wide Cas9-knockout screen. I will develop RNA aptamer technology to visualise and track single RNA molecules suffering from poly(A) read-through. I will elucidate why transcription termination of some cellular and all viral genes remains unaltered throughout infection. I hypothesize that the alterations in RNA processing are depicted by specific changes in RNA Polymerase II CTD phosphorylation and in the associated proteins. I will characterise these dynamic changes using mNET-seq and quantitative proteomics. Finally, data-driven quantitative bioinformatic modelling will detail how the coupling of RNA synthesis, processing, export, stability and translation is orchestrated by HSV-1.
Max ERC Funding
1 994 375 €
Duration
Start date: 2017-05-01, End date: 2022-04-30
Project acronym Honeyguides-Humans
Project How a mutualism evolves: learning, coevolution, and their ecosystem consequences in human-honeyguide interactions
Researcher (PI) Claire Noelle SPOTTISWOODE
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Consolidator Grant (CoG), LS8, ERC-2016-COG
Summary Species interactions such as mutualism, parasitism and predation underpin much of life’s diversity. We aim to understand the mechanistic role of learnt traits in the origin and maintenance of mutualistic interactions between species, and to test their evolutionary and ecological consequences. To do so, we shall study a remarkable mutualism: the foraging partnership between an African bird species, the greater honeyguide Indicator indicator, and the human honey-hunters whom it guides to bees’ nests. Honeyguides know where bees’ nests are located and like to eat beeswax; humans have the ability to subdue the bees and open the nest, thus exposing beeswax for the honeyguides and honey for the humans. This model system gives us a wonderful opportunity to study mutualisms, because local human and honeyguide populations vary strikingly in whether and how they interact, and because we can readily manipulate these interactions experimentally. We have already demonstrated that it is fully feasible to carry out observational and experimental work at a study site we have established in cooperation with a honey-hunting community in northern Mozambique. Here, and at a series of comparative field sites we have identified in south-eastern Africa, we shall ask: is learning involved in maintaining a geographical mosaic of honeyguide adaptation to local human cultures? How does reciprocal communication between humans and honeyguides mediate their interactions? What are the effects of cultural co-extinctions on each partner and their ecosystems, and how quickly can such cultures be re-ignited following their loss? In so doing we shall test for the first time the hypothesis that reciprocal learning can give rise to matching cultural traits between interacting species. Understanding the role of such phenotypic plasticity is crucial to explain how and why the outcome of species interactions varies in space and time, and to predict how they will respond to a rapidly changing world.
Summary
Species interactions such as mutualism, parasitism and predation underpin much of life’s diversity. We aim to understand the mechanistic role of learnt traits in the origin and maintenance of mutualistic interactions between species, and to test their evolutionary and ecological consequences. To do so, we shall study a remarkable mutualism: the foraging partnership between an African bird species, the greater honeyguide Indicator indicator, and the human honey-hunters whom it guides to bees’ nests. Honeyguides know where bees’ nests are located and like to eat beeswax; humans have the ability to subdue the bees and open the nest, thus exposing beeswax for the honeyguides and honey for the humans. This model system gives us a wonderful opportunity to study mutualisms, because local human and honeyguide populations vary strikingly in whether and how they interact, and because we can readily manipulate these interactions experimentally. We have already demonstrated that it is fully feasible to carry out observational and experimental work at a study site we have established in cooperation with a honey-hunting community in northern Mozambique. Here, and at a series of comparative field sites we have identified in south-eastern Africa, we shall ask: is learning involved in maintaining a geographical mosaic of honeyguide adaptation to local human cultures? How does reciprocal communication between humans and honeyguides mediate their interactions? What are the effects of cultural co-extinctions on each partner and their ecosystems, and how quickly can such cultures be re-ignited following their loss? In so doing we shall test for the first time the hypothesis that reciprocal learning can give rise to matching cultural traits between interacting species. Understanding the role of such phenotypic plasticity is crucial to explain how and why the outcome of species interactions varies in space and time, and to predict how they will respond to a rapidly changing world.
Max ERC Funding
1 998 885 €
Duration
Start date: 2017-06-01, End date: 2022-05-31
