Project acronym AAREA
Project The Archaeology of Agricultural Resilience in Eastern Africa
Researcher (PI) Daryl Stump
Host Institution (HI) UNIVERSITY OF YORK
Country United Kingdom
Call Details Starting Grant (StG), SH6, ERC-2013-StG
Summary "The twin concepts of sustainability and conservation that are so pivotal within current debates regarding economic development and biodiversity protection both contain an inherent temporal dimension, since both refer to the need to balance short-term gains with long-term resource maintenance. Proponents of resilience theory and of development based on ‘indigenous knowledge’ have thus argued for the necessity of including archaeological, historical and palaeoenvironmental components within development project design. Indeed, some have argued that archaeology should lead these interdisciplinary projects on the grounds that it provides the necessary time depth and bridges the social and natural sciences. The project proposed here accepts this logic and endorses this renewed contemporary relevance of archaeological research. However, it also needs to be admitted that moving beyond critiques of the misuse of historical data presents significant hurdles. When presenting results outside the discipline, for example, archaeological projects tend to downplay the poor archaeological visibility of certain agricultural practices, and computer models designed to test sustainability struggle to adequately account for local cultural preferences. This field will therefore not progress unless there is a frank appraisal of archaeology’s strengths and weaknesses. This project will provide this assessment by employing a range of established and groundbreaking archaeological and modelling techniques to examine the development of two east Africa agricultural systems: one at the abandoned site of Engaruka in Tanzania, commonly seen as an example of resource mismanagement and ecological collapse; and another at the current agricultural landscape in Konso, Ethiopia, described by the UN FAO as one of a select few African “lessons from the past”. The project thus aims to assess the sustainability of these systems, but will also assess the role archaeology can play in such debates worldwide."
Summary
"The twin concepts of sustainability and conservation that are so pivotal within current debates regarding economic development and biodiversity protection both contain an inherent temporal dimension, since both refer to the need to balance short-term gains with long-term resource maintenance. Proponents of resilience theory and of development based on ‘indigenous knowledge’ have thus argued for the necessity of including archaeological, historical and palaeoenvironmental components within development project design. Indeed, some have argued that archaeology should lead these interdisciplinary projects on the grounds that it provides the necessary time depth and bridges the social and natural sciences. The project proposed here accepts this logic and endorses this renewed contemporary relevance of archaeological research. However, it also needs to be admitted that moving beyond critiques of the misuse of historical data presents significant hurdles. When presenting results outside the discipline, for example, archaeological projects tend to downplay the poor archaeological visibility of certain agricultural practices, and computer models designed to test sustainability struggle to adequately account for local cultural preferences. This field will therefore not progress unless there is a frank appraisal of archaeology’s strengths and weaknesses. This project will provide this assessment by employing a range of established and groundbreaking archaeological and modelling techniques to examine the development of two east Africa agricultural systems: one at the abandoned site of Engaruka in Tanzania, commonly seen as an example of resource mismanagement and ecological collapse; and another at the current agricultural landscape in Konso, Ethiopia, described by the UN FAO as one of a select few African “lessons from the past”. The project thus aims to assess the sustainability of these systems, but will also assess the role archaeology can play in such debates worldwide."
Max ERC Funding
1 196 701 €
Duration
Start date: 2014-02-01, End date: 2018-01-31
Project acronym Coupled gene circuit
Project Dynamics, noise, and coupling in gene circuit modules
Researcher (PI) James Charles Wallace Locke
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Country United Kingdom
Call Details Starting Grant (StG), LS2, ERC-2013-StG
Summary Cells must integrate output from multiple genetic circuits in order to correctly control cellular processes. Despite much work characterizing regulation in these circuits, how circuits interact to control global cellular programs remains unclear. This is particularly true given that recent research at the single cell level has revealed that genetic circuits often generate variable or stochastic regulation dynamics. In this proposal we will use a multi-disciplinary approach, combining modelling and time-lapse microscopy, to investigate how cells can robustly integrate signals from multiple dynamic genetic circuits. In particular we will answer the following questions: 1) What types of dynamic signal encoding strategies are available for the cell? 2) What are the benefits of dynamic gene activation, whether stochastic or oscillatory, to the cell? 3) How do cells couple and integrate output from diverse gene modules despite the noise and variability observed in gene circuit dynamics?
We will study these questions using 2 key model systems. In Aim 1, we will examine stochastic pulse regulation dynamics and coupling between alternative sigma factors in B. subtilis. Our preliminary data has revealed that multiple B. subtilis sigma factors stochastically pulse under stress. We will look for evidence of any coupling or interactions between these stochastic pulse circuits. This system will serve as a model for how a cell uses stochastic pulsing to control diverse cellular processes. In Aim 2, we will examine coupling between a deterministic oscillator, the circadian clock, and multiple other key pathways in Cyanobacteria. We will examine how the cell can dynamically couple multiple cellular processes using an oscillating signal. This work will provide an excellent base for Aim 3, in which we will use synthetic biology approaches to develop ‘bottom up’ tests of generation of novel dynamic coupling strategies.
Summary
Cells must integrate output from multiple genetic circuits in order to correctly control cellular processes. Despite much work characterizing regulation in these circuits, how circuits interact to control global cellular programs remains unclear. This is particularly true given that recent research at the single cell level has revealed that genetic circuits often generate variable or stochastic regulation dynamics. In this proposal we will use a multi-disciplinary approach, combining modelling and time-lapse microscopy, to investigate how cells can robustly integrate signals from multiple dynamic genetic circuits. In particular we will answer the following questions: 1) What types of dynamic signal encoding strategies are available for the cell? 2) What are the benefits of dynamic gene activation, whether stochastic or oscillatory, to the cell? 3) How do cells couple and integrate output from diverse gene modules despite the noise and variability observed in gene circuit dynamics?
We will study these questions using 2 key model systems. In Aim 1, we will examine stochastic pulse regulation dynamics and coupling between alternative sigma factors in B. subtilis. Our preliminary data has revealed that multiple B. subtilis sigma factors stochastically pulse under stress. We will look for evidence of any coupling or interactions between these stochastic pulse circuits. This system will serve as a model for how a cell uses stochastic pulsing to control diverse cellular processes. In Aim 2, we will examine coupling between a deterministic oscillator, the circadian clock, and multiple other key pathways in Cyanobacteria. We will examine how the cell can dynamically couple multiple cellular processes using an oscillating signal. This work will provide an excellent base for Aim 3, in which we will use synthetic biology approaches to develop ‘bottom up’ tests of generation of novel dynamic coupling strategies.
Max ERC Funding
1 499 571 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym GRASP
Project The evolution of the human hand: grasping trees and tools
Researcher (PI) Tracy Lynne Kivell
Host Institution (HI) UNIVERSITY OF KENT
Country United Kingdom
Call Details Starting Grant (StG), SH6, ERC-2013-StG
Summary The unique manipulative abilities of the human hand have fascinated scientists since the time of Darwin. However, we know little about how these unique abilities evolved because we have lacked, (1) the necessary fossil human (hominin) evidence and (2) the appropriate methods to investigate if, when and how our early ancestors used their hands for locomotion (climbing) and manipulation (tool-use). The GRASP project will use novel morphological, experimental and biomechanical methods to investigate different locomotor and manipulative behaviours in humans and other apes, and will use this knowledge to reconstruct hand use in the most complete early hominin hand fossils, those of Australopithecus sediba. The goal of GRASP is to determine the evolutionary history of the human hand by addressing two fundamental, yet unresolved, questions: (1) Were our fossil hominin ancestors still using their hands for climbing? (2) When and in which fossil hominin species did stone tool-use and tool-making first evolve? These questions will be addressed via three objectives: First, microtomography and a novel, holistic method (MedTool®) will be used to analyse the internal bony structure of human, ape and fossil hominin hand bones. Second, collection of the necessary biomechanical data on (a) the loads experienced by the human hand during tool-use and tool-making, (b) hand use and hand postures used by African apes during locomotion in the wild and, (c) the loads experienced by the bonobo hand during arboreal locomotion. Third, data from the first two objectives will be used to adapt musculoskeletal models of the human and bonobo hand and, through the creation of 3D biomechanical (finite-element) models, simulate natural loading of individual hand bones in humans, bonobos and fossil hominins. With this detailed understanding of hand function, we will determine how the locomotor and manipulative behaviours of Au. sediba and other early hominins shaped the evolution of the human hand.
Summary
The unique manipulative abilities of the human hand have fascinated scientists since the time of Darwin. However, we know little about how these unique abilities evolved because we have lacked, (1) the necessary fossil human (hominin) evidence and (2) the appropriate methods to investigate if, when and how our early ancestors used their hands for locomotion (climbing) and manipulation (tool-use). The GRASP project will use novel morphological, experimental and biomechanical methods to investigate different locomotor and manipulative behaviours in humans and other apes, and will use this knowledge to reconstruct hand use in the most complete early hominin hand fossils, those of Australopithecus sediba. The goal of GRASP is to determine the evolutionary history of the human hand by addressing two fundamental, yet unresolved, questions: (1) Were our fossil hominin ancestors still using their hands for climbing? (2) When and in which fossil hominin species did stone tool-use and tool-making first evolve? These questions will be addressed via three objectives: First, microtomography and a novel, holistic method (MedTool®) will be used to analyse the internal bony structure of human, ape and fossil hominin hand bones. Second, collection of the necessary biomechanical data on (a) the loads experienced by the human hand during tool-use and tool-making, (b) hand use and hand postures used by African apes during locomotion in the wild and, (c) the loads experienced by the bonobo hand during arboreal locomotion. Third, data from the first two objectives will be used to adapt musculoskeletal models of the human and bonobo hand and, through the creation of 3D biomechanical (finite-element) models, simulate natural loading of individual hand bones in humans, bonobos and fossil hominins. With this detailed understanding of hand function, we will determine how the locomotor and manipulative behaviours of Au. sediba and other early hominins shaped the evolution of the human hand.
Max ERC Funding
1 618 253 €
Duration
Start date: 2014-03-01, End date: 2019-02-28
Project acronym JAGEUROPE
Project "The Jagiellonians: Dynasty, Identity and Memory in Central Europe"
Researcher (PI) Natalia Magdalena Nowakowska
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Starting Grant (StG), SH6, ERC-2013-StG
Summary "This ERC Starter Grant project will fund an interdisciplinary, transnational and groundbreaking study of the Jagiellonian dynasty (c.1386-1596) and its role, and legacy, in the development of identity in what we now call Central Europe. One of the most spectacularly successful of early modern dynasties, comparable only to the Habsburgs, in 1500 the Jagiellonians ruled a third of continental Europe, an area comprising no fewer than 14 present-day states. Uniquely among European dynasties in this period, the Jagiellonians created a dynastic regional hegemony, a geographical ‘bloc’ of neighbouring monarchies. Our knowledge of the Jagiellonians is, however, limited and highly fragmented along both national and disciplinary lines. The project will provide the first treatment of this leading Renaissance-era dynasty as a supra-national entity; it will offer a major new investigation of Renaissance dynasty itself as a political and cultural institution; explore the part played by the Jagiellonians in the evolution of pre-modern local or 'national' and regional identities, and investigate the ways in which divergent memories of their rule have, from 1596 onwards, shaped modern national identities in Central Europe. The project will transcend scholarly divisions – between disciplines (e.g. art history, anthropology, political history), between period specialisations (late medieval, early modern, modern) and between individual national historiographies (Polish, German, Czech etc.), to offer a metahistory of the meanings attributed to this landmark European dynasty, from the founder Jogaila (d.1434) to Radek Sikorski, Poland’s current foreign minister. The research will be undertaken by a multi-lingual team of 5 post-doctoral researchers, led by the PI, drawing on a range of written and visual sources produced by and about the Jagiellonians over six centuries."
Summary
"This ERC Starter Grant project will fund an interdisciplinary, transnational and groundbreaking study of the Jagiellonian dynasty (c.1386-1596) and its role, and legacy, in the development of identity in what we now call Central Europe. One of the most spectacularly successful of early modern dynasties, comparable only to the Habsburgs, in 1500 the Jagiellonians ruled a third of continental Europe, an area comprising no fewer than 14 present-day states. Uniquely among European dynasties in this period, the Jagiellonians created a dynastic regional hegemony, a geographical ‘bloc’ of neighbouring monarchies. Our knowledge of the Jagiellonians is, however, limited and highly fragmented along both national and disciplinary lines. The project will provide the first treatment of this leading Renaissance-era dynasty as a supra-national entity; it will offer a major new investigation of Renaissance dynasty itself as a political and cultural institution; explore the part played by the Jagiellonians in the evolution of pre-modern local or 'national' and regional identities, and investigate the ways in which divergent memories of their rule have, from 1596 onwards, shaped modern national identities in Central Europe. The project will transcend scholarly divisions – between disciplines (e.g. art history, anthropology, political history), between period specialisations (late medieval, early modern, modern) and between individual national historiographies (Polish, German, Czech etc.), to offer a metahistory of the meanings attributed to this landmark European dynasty, from the founder Jogaila (d.1434) to Radek Sikorski, Poland’s current foreign minister. The research will be undertaken by a multi-lingual team of 5 post-doctoral researchers, led by the PI, drawing on a range of written and visual sources produced by and about the Jagiellonians over six centuries."
Max ERC Funding
1 407 037 €
Duration
Start date: 2013-10-01, End date: 2018-09-30
Project acronym MemRegPro
Project How Membrane Physical Properties and Cortical Actin Regulate Protein Interactions During T Cell Signalling
Researcher (PI) Dylan Myers Owen
Host Institution (HI) KING'S COLLEGE LONDON
Country United Kingdom
Call Details Starting Grant (StG), LS6, ERC-2013-StG
Summary The overall aim of this project is to identify key biophysical mechanisms that control the spatial arrangement of signalling proteins and membrane lipids in the regulation of T cell activation. During an immune response, T cells are activated in response to antigenic peptides in a process that requires the formation of multi-molecular signalling complexes. It is known that many T cell signalling proteins (such as the kinase Lck and the scaffold protein LAT) are not randomly distributed within the plasma membrane thus giving rise to lateral organization which affects signalling efficiency. However, the biophysical mechanism(s) that control protein distributions and hence the rate of molecular interactions remains poorly understood. Two of the principal mechanisms are compartmentalisation of the membrane by lipid microdomains (the ‘lipid raft’ hypothesis) and by the cortical actin meshwork (the ‘picket-fence’ model). The two key technologies needed to unravel how protein clustering and the biophysical properties of the lipid bilayer regulate specific interactions at the molecular level have now been developed. These are single-molecule, super-resolution localisation microscopy and quantification of membrane biophysical properties using new-generation environmentally sensitive fluorescent probes. Using these methods, the proposed project will generate unique insights into the biophysical mechanisms that govern the formation of the protein clusters and complexes during early T cell signalling events. This knowledge is critical to our understanding of the molecular basis of T cell activation during the immune response and has potential applications in the development of therapeutic treatments for a range of conditions.
Summary
The overall aim of this project is to identify key biophysical mechanisms that control the spatial arrangement of signalling proteins and membrane lipids in the regulation of T cell activation. During an immune response, T cells are activated in response to antigenic peptides in a process that requires the formation of multi-molecular signalling complexes. It is known that many T cell signalling proteins (such as the kinase Lck and the scaffold protein LAT) are not randomly distributed within the plasma membrane thus giving rise to lateral organization which affects signalling efficiency. However, the biophysical mechanism(s) that control protein distributions and hence the rate of molecular interactions remains poorly understood. Two of the principal mechanisms are compartmentalisation of the membrane by lipid microdomains (the ‘lipid raft’ hypothesis) and by the cortical actin meshwork (the ‘picket-fence’ model). The two key technologies needed to unravel how protein clustering and the biophysical properties of the lipid bilayer regulate specific interactions at the molecular level have now been developed. These are single-molecule, super-resolution localisation microscopy and quantification of membrane biophysical properties using new-generation environmentally sensitive fluorescent probes. Using these methods, the proposed project will generate unique insights into the biophysical mechanisms that govern the formation of the protein clusters and complexes during early T cell signalling events. This knowledge is critical to our understanding of the molecular basis of T cell activation during the immune response and has potential applications in the development of therapeutic treatments for a range of conditions.
Max ERC Funding
1 402 513 €
Duration
Start date: 2014-02-01, End date: 2019-01-31
Project acronym NanoScope
Project Optical imaging of nanoscopic dynamics and potentials
Researcher (PI) Philipp Kukura
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Country United Kingdom
Call Details Starting Grant (StG), LS1, ERC-2013-StG
Summary I propose to develop and apply a novel approach to optical microscopy to enable the direct visualization and study of dynamics on the nanoscale in biological and condensed matter physics. Given the speed with which nanoscopic objects move at ambient condition, this requires simultaneously very fast (ms) and precise (nm) imaging. The challenge is to avoid excessive perturbation of the system and enable imaging in biologically compatible environments without compromising imaging performance by pushing interferometric scattering to its theoretical limits.
Using these advanced capabilities, I will study the dynamics and thereby the structure-function relationships in three fundamental systems that are currently not captured by even the most advanced biophysical approaches. These include: (1) the flexibility of DNA on short length scales, (2) diffusion in artificial and cellular membranes and (3) the three-dimensional power stroke of molecular motors such as myosin and kinesin.
Fundamentally, this work aims to develop and establish a high-speed, non-invasive camera on the nanoscale that will enable us to study and eventually understand nanoscopic motion, dynamics and potentials on the relevant, rather than currently achievable, size and time scales.
Summary
I propose to develop and apply a novel approach to optical microscopy to enable the direct visualization and study of dynamics on the nanoscale in biological and condensed matter physics. Given the speed with which nanoscopic objects move at ambient condition, this requires simultaneously very fast (ms) and precise (nm) imaging. The challenge is to avoid excessive perturbation of the system and enable imaging in biologically compatible environments without compromising imaging performance by pushing interferometric scattering to its theoretical limits.
Using these advanced capabilities, I will study the dynamics and thereby the structure-function relationships in three fundamental systems that are currently not captured by even the most advanced biophysical approaches. These include: (1) the flexibility of DNA on short length scales, (2) diffusion in artificial and cellular membranes and (3) the three-dimensional power stroke of molecular motors such as myosin and kinesin.
Fundamentally, this work aims to develop and establish a high-speed, non-invasive camera on the nanoscale that will enable us to study and eventually understand nanoscopic motion, dynamics and potentials on the relevant, rather than currently achievable, size and time scales.
Max ERC Funding
1 498 352 €
Duration
Start date: 2014-01-01, End date: 2018-12-31
Project acronym RELYUBL
Project Regulation of lymphocyte biology by ubiquitin and ubiquitin like modifiers
Researcher (PI) Yogesh Kulathu
Host Institution (HI) UNIVERSITY OF DUNDEE
Country United Kingdom
Call Details Starting Grant (StG), LS6, ERC-2015-STG
Summary T lymphocytes are key cells of the adaptive immune system that protect us against pathogens and malignant cells. T cell activation and differentiation are tightly controlled processes and deregulation can result in lymphomas, autoimmunity and inflammation. Hence, the biochemical events regulating lymphocyte biology have long been a topic of intense research, which has been focussed predominantly on protein phosphorylation. I hypothesize that there are crucial roles undiscovered in T cells for other posttranslational modifications (PTMs) such as ubiquitin (Ub) and Ub-like proteins (UBLs). The importance of ubiquitylation in adaptive immunity is implied by the severe immunological disorders observed when components of the Ub system are disrupted in lymphocytes. Genetic approaches in mice give a limited understanding about the roles of these modifiers and do not reveal the full extent to which Ub and UBLs regulate lymphocyte biology. Deterred by the complexity of the Ub system, the field has not yet tackled the daunting challenge of systematically investigating these modifiers in vivo. The goal of this proposal is to define how T cell function and immune responses are regulated by Ub and UBL signalling networks. To pioneer substantial progress in this area, we will develop new methods to identify and characterize currently unknown recognition modules for the different modifications. We will elucidate the Ub and UBL modified proteome in lymphocytes and characterize dynamic changes of these PTMs during T cell activation. By focussing on enzymes that remove the modifications we will discover how these PTMs are regulated and define Ub and UBL-dependent signalling nodes. Each phase of the work will deliver fundamentally novel mechanistic insights into these PTMs while rewriting current concepts of signalling in lymphocytes. Ultimately, this work will inform therapies seeking to target lymphocyte activity in disease.
Summary
T lymphocytes are key cells of the adaptive immune system that protect us against pathogens and malignant cells. T cell activation and differentiation are tightly controlled processes and deregulation can result in lymphomas, autoimmunity and inflammation. Hence, the biochemical events regulating lymphocyte biology have long been a topic of intense research, which has been focussed predominantly on protein phosphorylation. I hypothesize that there are crucial roles undiscovered in T cells for other posttranslational modifications (PTMs) such as ubiquitin (Ub) and Ub-like proteins (UBLs). The importance of ubiquitylation in adaptive immunity is implied by the severe immunological disorders observed when components of the Ub system are disrupted in lymphocytes. Genetic approaches in mice give a limited understanding about the roles of these modifiers and do not reveal the full extent to which Ub and UBLs regulate lymphocyte biology. Deterred by the complexity of the Ub system, the field has not yet tackled the daunting challenge of systematically investigating these modifiers in vivo. The goal of this proposal is to define how T cell function and immune responses are regulated by Ub and UBL signalling networks. To pioneer substantial progress in this area, we will develop new methods to identify and characterize currently unknown recognition modules for the different modifications. We will elucidate the Ub and UBL modified proteome in lymphocytes and characterize dynamic changes of these PTMs during T cell activation. By focussing on enzymes that remove the modifications we will discover how these PTMs are regulated and define Ub and UBL-dependent signalling nodes. Each phase of the work will deliver fundamentally novel mechanistic insights into these PTMs while rewriting current concepts of signalling in lymphocytes. Ultimately, this work will inform therapies seeking to target lymphocyte activity in disease.
Max ERC Funding
1 499 987 €
Duration
Start date: 2016-06-01, End date: 2021-05-31
Project acronym RivRNAStructureDecay
Project Investigating the role of in vivo RNA structure in RNA degradation
Researcher (PI) Yiliang Ding
Host Institution (HI) JOHN INNES CENTRE
Country United Kingdom
Call Details Starting Grant (StG), LS1, ERC-2015-STG
Summary RNA plays a central role in the regulation of gene expression. The basal levels of RNA in a cell depend on the ratio between RNA synthesis and RNA degradation. RNA degradation is an active and critical process that dictates RNA levels and in part controls the relative levels of gene expression. However, despite many years of research, important and perplexing questions remain about RNA stability. Even when comparable RNA degradation processes are involved individual RNAs can have distinct decay rates and the mechanisms that control such distinctive rates are unknown. RNA structure is likely to be intrinsic to our understanding of the RNA features that govern stability and until very recently our ability to measure the true in vivo RNA structure has been incredibly limited.
The aim of this proposal is to understand the role of RNA structure in the regulation of RNA degradation and determine the RNA structural features that regulate the degradation pathways. We propose an ambitious programme that will pursue the following objectives:
1. Globally investigate RNA structural features and compare these to RNA degradation in vivo.
2. Decipher the mechanism of no go decay (NGD) via identifying the role of the G-quadruplex.
3. Determine the role of RNA structure in the miRNA pathway for both miRNA precursor processing and miRNA-directed processing.
This proposed study will reveal the fundamental function of RNA structures in RNA degradation. Two novel in vivo RNA structural profiling platforms will be established. The combination of RNA structural profiling, with existing ribosome profiling and the RNA degradome will generate a global view of RNA structural features and their relationship with RNA degradation. This proposed study will fill a significant gap in our understanding of the mechanisms of RNA degradation in plants and this will likely impact RNA studies in all eukaryotes.
Summary
RNA plays a central role in the regulation of gene expression. The basal levels of RNA in a cell depend on the ratio between RNA synthesis and RNA degradation. RNA degradation is an active and critical process that dictates RNA levels and in part controls the relative levels of gene expression. However, despite many years of research, important and perplexing questions remain about RNA stability. Even when comparable RNA degradation processes are involved individual RNAs can have distinct decay rates and the mechanisms that control such distinctive rates are unknown. RNA structure is likely to be intrinsic to our understanding of the RNA features that govern stability and until very recently our ability to measure the true in vivo RNA structure has been incredibly limited.
The aim of this proposal is to understand the role of RNA structure in the regulation of RNA degradation and determine the RNA structural features that regulate the degradation pathways. We propose an ambitious programme that will pursue the following objectives:
1. Globally investigate RNA structural features and compare these to RNA degradation in vivo.
2. Decipher the mechanism of no go decay (NGD) via identifying the role of the G-quadruplex.
3. Determine the role of RNA structure in the miRNA pathway for both miRNA precursor processing and miRNA-directed processing.
This proposed study will reveal the fundamental function of RNA structures in RNA degradation. Two novel in vivo RNA structural profiling platforms will be established. The combination of RNA structural profiling, with existing ribosome profiling and the RNA degradome will generate a global view of RNA structural features and their relationship with RNA degradation. This proposed study will fill a significant gap in our understanding of the mechanisms of RNA degradation in plants and this will likely impact RNA studies in all eukaryotes.
Max ERC Funding
1 499 986 €
Duration
Start date: 2016-01-01, End date: 2021-12-31
Project acronym Token Communities
Project Token Communities in the Ancient Mediterranean
Researcher (PI) Clare Phillpa Rowan
Host Institution (HI) THE UNIVERSITY OF WARWICK
Country United Kingdom
Call Details Starting Grant (StG), SH6, ERC-2015-STG
Summary This project will provide the first comprehensive analysis of the role played by tokens in the ancient Mediterranean. Tokens are frequently found on archaeological sites and within museum collections, but are little studied and poorly understood. These objects played a central role in cultural, religious, political and economic life in antiquity; closer study of these objects is thus imperative in gaining a fuller picture of the ancient world and its cultural legacy. An interdisciplinary team will examine tokens and their contexts within the ancient world, focusing on the periods when they are in highest use: the Hellenistic period (postdoctoral researcher) and the Roman world (PI and 2 PhD students).
The project will combine an analysis of museum material with the known archaeological contexts of these objects. It will be the first project to approach these items in a cross regional and fully contextualised manner. This approach will enable researchers to better define what tokens were in antiquity, and what roles they played. Moreover, through a careful consideration of type, context, and distribution, the project will also explore how these objects actively contributed to the generation of different types of community. The envisaged outcomes will provide a basis for the study of tokens more broadly, generating insights that will inform the display, scholarly use and understanding of these objects within museums and other spaces. The exploration of how tokens and token-communities within antiquity existed alongside official currencies and groups will also provide an important historical parallel for the contemporary development of alternative currencies, their associated values, and communities.
Summary
This project will provide the first comprehensive analysis of the role played by tokens in the ancient Mediterranean. Tokens are frequently found on archaeological sites and within museum collections, but are little studied and poorly understood. These objects played a central role in cultural, religious, political and economic life in antiquity; closer study of these objects is thus imperative in gaining a fuller picture of the ancient world and its cultural legacy. An interdisciplinary team will examine tokens and their contexts within the ancient world, focusing on the periods when they are in highest use: the Hellenistic period (postdoctoral researcher) and the Roman world (PI and 2 PhD students).
The project will combine an analysis of museum material with the known archaeological contexts of these objects. It will be the first project to approach these items in a cross regional and fully contextualised manner. This approach will enable researchers to better define what tokens were in antiquity, and what roles they played. Moreover, through a careful consideration of type, context, and distribution, the project will also explore how these objects actively contributed to the generation of different types of community. The envisaged outcomes will provide a basis for the study of tokens more broadly, generating insights that will inform the display, scholarly use and understanding of these objects within museums and other spaces. The exploration of how tokens and token-communities within antiquity existed alongside official currencies and groups will also provide an important historical parallel for the contemporary development of alternative currencies, their associated values, and communities.
Max ERC Funding
1 033 723 €
Duration
Start date: 2016-06-01, End date: 2021-08-31
Project acronym TransposonsReprogram
Project How retrotransposons remodel the genome during early development and reprogramming
Researcher (PI) HELEN MARY Rowe
Host Institution (HI) QUEEN MARY UNIVERSITY OF LONDON
Country United Kingdom
Call Details Starting Grant (StG), LS2, ERC-2015-STG
Summary Retrotransposons (RTNs) are ancient viruses that have stably integrated themselves into mammalian genomes and they now occupy around half of the human or mouse genome. These mobile genetic elements that have coevolved with us drive evolution by creating new genes and plasticity of genomes. Exciting data including ours has shown that even RTNs that are no longer active retain enhancer, promoter or repressor sequences that regulate developmental genes, through largely uncharacterized transcription factors. We have employed CRISPR/Cas9 gene disruption to determine that Zfp37 and Zfp819 bind to and regulate RTNs in mouse embryonic stem cells (ESCs). Identification of these zinc finger proteins (ZFPs) now allows us to ask new questions about how RTNs have been co-opted to orchestrate gene circuits in vitro and in vivo. Both these factors have already been implicated to play a role in reprogramming or genome integrity.
We hypothesize that RTNs have been co-opted to remodel the genome by acting as structural platforms that recruit transcription factors like Zfp37 and Zfp819. We will test this hypothesis assessing the role of RTNs and these two ZFPs in three dynamic contexts where the genome is remodelled. These are in ESC differentiation to neurons, in reprogramming and in early mouse development, three scenarios where RTNs have been documented to become expressed and serve an unknown function.
This work will exploit mouse development to unravel the mechanism of how RTNs remodel the genome. It will help us to understand how ZFPs can be engaged to reprogram cells and in stem-cell therapies, and will explain more broadly how RTNs, which dominate our genomes, control cell fate.
Summary
Retrotransposons (RTNs) are ancient viruses that have stably integrated themselves into mammalian genomes and they now occupy around half of the human or mouse genome. These mobile genetic elements that have coevolved with us drive evolution by creating new genes and plasticity of genomes. Exciting data including ours has shown that even RTNs that are no longer active retain enhancer, promoter or repressor sequences that regulate developmental genes, through largely uncharacterized transcription factors. We have employed CRISPR/Cas9 gene disruption to determine that Zfp37 and Zfp819 bind to and regulate RTNs in mouse embryonic stem cells (ESCs). Identification of these zinc finger proteins (ZFPs) now allows us to ask new questions about how RTNs have been co-opted to orchestrate gene circuits in vitro and in vivo. Both these factors have already been implicated to play a role in reprogramming or genome integrity.
We hypothesize that RTNs have been co-opted to remodel the genome by acting as structural platforms that recruit transcription factors like Zfp37 and Zfp819. We will test this hypothesis assessing the role of RTNs and these two ZFPs in three dynamic contexts where the genome is remodelled. These are in ESC differentiation to neurons, in reprogramming and in early mouse development, three scenarios where RTNs have been documented to become expressed and serve an unknown function.
This work will exploit mouse development to unravel the mechanism of how RTNs remodel the genome. It will help us to understand how ZFPs can be engaged to reprogram cells and in stem-cell therapies, and will explain more broadly how RTNs, which dominate our genomes, control cell fate.
Max ERC Funding
1 499 055 €
Duration
Start date: 2016-05-01, End date: 2022-12-31
