Project acronym BFTERRA
Project Biogenesis and Functions of Telomeric Repeat-containing RNA
Researcher (PI) Claus Maria Azzalin
Host Institution (HI) EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Call Details Starting Grant (StG), LS1, ERC-2009-StG
Summary Telomeres are heterochromatic nucleoprotein complexes located at the end of linear eukaryotic chromosomes. Contrarily to a longstanding dogma, we have recently demonstrated that mammalian telomeres are transcribed into TElomeric Repeat containing RNA (TERRA) molecules. TERRA transcripts contain telomeric RNA repeats and are produced at least in part by DNA-dependent RNA polymerase II-mediated transcription of telomeric DNA. TERRA molecules form discrete nuclear foci that co-localize with telomeric heterochromatin in both interphase and transcriptionally inactive metaphase cells. This indicates that TERRA is an integral component of telomeres and suggests that TERRA might participate in maintaining proper telomere heterochromatin. We will use a variety of biochemistry, cell biology, molecular biology and microscopy based approaches applied to cultured mammalian cells and to the yeast Schizosaccharomyces pombe, to achieve four distinct major goals: i) We will over-express or deplete TERRA in mammalian cells in order to characterize the molecular details of putative TERRA-associated functions in maintaining normal telomere structure and function; ii) We will locate TERRA promoter regions on different human chromosome ends; iii) We will generate mammalian cellular systems in which to study artificially seeded telomeres that can be transcribed in an inducible fashion; iv) We will identify physiological regulators of TERRA by analyzing it in mammalian cultured cells where the functions of candidate factors are compromised. In parallel, taking advantage of the recent discovery of TERRA also in fission yeast, we will systematically analyze TERRA levels in fission yeast mutants derived from a complete gene knockout collection. The study of TERRA regulation and function at chromosome ends will strongly contribute to our understanding of how telomeres are maintained and will help to clarify the general functions of mammalian non-coding RNAs.
Summary
Telomeres are heterochromatic nucleoprotein complexes located at the end of linear eukaryotic chromosomes. Contrarily to a longstanding dogma, we have recently demonstrated that mammalian telomeres are transcribed into TElomeric Repeat containing RNA (TERRA) molecules. TERRA transcripts contain telomeric RNA repeats and are produced at least in part by DNA-dependent RNA polymerase II-mediated transcription of telomeric DNA. TERRA molecules form discrete nuclear foci that co-localize with telomeric heterochromatin in both interphase and transcriptionally inactive metaphase cells. This indicates that TERRA is an integral component of telomeres and suggests that TERRA might participate in maintaining proper telomere heterochromatin. We will use a variety of biochemistry, cell biology, molecular biology and microscopy based approaches applied to cultured mammalian cells and to the yeast Schizosaccharomyces pombe, to achieve four distinct major goals: i) We will over-express or deplete TERRA in mammalian cells in order to characterize the molecular details of putative TERRA-associated functions in maintaining normal telomere structure and function; ii) We will locate TERRA promoter regions on different human chromosome ends; iii) We will generate mammalian cellular systems in which to study artificially seeded telomeres that can be transcribed in an inducible fashion; iv) We will identify physiological regulators of TERRA by analyzing it in mammalian cultured cells where the functions of candidate factors are compromised. In parallel, taking advantage of the recent discovery of TERRA also in fission yeast, we will systematically analyze TERRA levels in fission yeast mutants derived from a complete gene knockout collection. The study of TERRA regulation and function at chromosome ends will strongly contribute to our understanding of how telomeres are maintained and will help to clarify the general functions of mammalian non-coding RNAs.
Max ERC Funding
1 602 600 €
Duration
Start date: 2009-10-01, End date: 2014-09-30
Project acronym BIDECASEOX
Project Bio-inspired Design of Catalysts for Selective Oxidations of C-H and C=C Bonds
Researcher (PI) Miguel Costas Salgueiro
Host Institution (HI) UNIVERSITAT DE GIRONA
Call Details Starting Grant (StG), PE5, ERC-2009-StG
Summary The selective functionalization of C-H and C=C bonds remains a formidable unsolved problem, owing to their inert nature. Novel alkane and alkene oxidation reactions exhibiting good and/or unprecedented selectivities will have a big impact on bulk and fine chemistry by opening novel methodologies that will allow removal of protection-deprotection sequences, thus streamlining synthetic strategies. These goals are targeted in this project via design of iron and manganese catalysts inspired by structural elements of the active site of non-heme enzymes of the Rieske Dioxygenase family. Selectivity is pursued via rational design of catalysts that will exploit substrate recognition-exclusion phenomena, and control over proton and electron affinity of the active species. Moreover, these catalysts will employ H2O2 as oxidant, and will operate under mild conditions (pressure and temperature). The fundamental mechanistic aspects of the catalytic reactions, and the species implicated in C-H and C=C oxidation events will also be studied with the aim of building on the necessary knowledge to design future generations of catalysts, and provide models to understand the chemistry taking place in non-heme iron and manganese-dependent oxygenases.
Summary
The selective functionalization of C-H and C=C bonds remains a formidable unsolved problem, owing to their inert nature. Novel alkane and alkene oxidation reactions exhibiting good and/or unprecedented selectivities will have a big impact on bulk and fine chemistry by opening novel methodologies that will allow removal of protection-deprotection sequences, thus streamlining synthetic strategies. These goals are targeted in this project via design of iron and manganese catalysts inspired by structural elements of the active site of non-heme enzymes of the Rieske Dioxygenase family. Selectivity is pursued via rational design of catalysts that will exploit substrate recognition-exclusion phenomena, and control over proton and electron affinity of the active species. Moreover, these catalysts will employ H2O2 as oxidant, and will operate under mild conditions (pressure and temperature). The fundamental mechanistic aspects of the catalytic reactions, and the species implicated in C-H and C=C oxidation events will also be studied with the aim of building on the necessary knowledge to design future generations of catalysts, and provide models to understand the chemistry taking place in non-heme iron and manganese-dependent oxygenases.
Max ERC Funding
1 299 998 €
Duration
Start date: 2009-11-01, End date: 2015-10-31
Project acronym BIOCARB
Project Carbonate Biomineralization in the Marine Environment: Paleo-climate proxies and the origin of vital effects
Researcher (PI) Anders Meibom
Host Institution (HI) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Call Details Advanced Grant (AdG), PE10, ERC-2009-AdG
Summary This interdisciplinary proposal has the objective to greatly enhance our understanding of fundamental biomineralization processes involved in the formation of calcium carbonates by marine organisms, such as corals, foraminifera and bivalves, in order to better understand vital effects. This is essential to the application of these carbonates as proxies for global (paleo-) environmental change. The core of the proposal is an experimental capability that I have pioneered during 2008: Dynamic stable isotopic labeling during formation of carbonate skeletons, tests, and shells, combined with NanoSIMS imaging. The NanoSIMS ion microprobe is a state-of-the-art analytical technology that allows precise elemental and isotopic imaging with a spatial resolution of ~100 nanometers. NanoSIMS imaging of the isotopic label(s) in the resulting biocarbonates and in associated cell-structures will be used to uncover cellular-level transport processes, timescales of formation of different biocarbonate components, as well as trace-elemental and isotopic fractionations. This will uncover the origin of vital effects. With this proposal, I establish a new scientific frontier and guarantee European leadership. The technical and scientific developments resulting from this work are broadly applicable and will radically change scientific ideas about marine carbonate biomineralization and compositional vital effects.
Summary
This interdisciplinary proposal has the objective to greatly enhance our understanding of fundamental biomineralization processes involved in the formation of calcium carbonates by marine organisms, such as corals, foraminifera and bivalves, in order to better understand vital effects. This is essential to the application of these carbonates as proxies for global (paleo-) environmental change. The core of the proposal is an experimental capability that I have pioneered during 2008: Dynamic stable isotopic labeling during formation of carbonate skeletons, tests, and shells, combined with NanoSIMS imaging. The NanoSIMS ion microprobe is a state-of-the-art analytical technology that allows precise elemental and isotopic imaging with a spatial resolution of ~100 nanometers. NanoSIMS imaging of the isotopic label(s) in the resulting biocarbonates and in associated cell-structures will be used to uncover cellular-level transport processes, timescales of formation of different biocarbonate components, as well as trace-elemental and isotopic fractionations. This will uncover the origin of vital effects. With this proposal, I establish a new scientific frontier and guarantee European leadership. The technical and scientific developments resulting from this work are broadly applicable and will radically change scientific ideas about marine carbonate biomineralization and compositional vital effects.
Max ERC Funding
2 182 000 €
Duration
Start date: 2010-07-01, End date: 2015-06-30
Project acronym BIOCOM
Project Biotic community attributes and ecosystem functioning: implications for predicting and mitigating global change impacts
Researcher (PI) Fernando Tomás Maestre Gil
Host Institution (HI) UNIVERSIDAD REY JUAN CARLOS
Call Details Starting Grant (StG), LS8, ERC-2009-StG
Summary Increases in nutrient availability and temperature, and changes in precipitation patterns and biodiversity are important components of global environmental change. Thus, it is imperative to understand their impacts on the functioning of natural ecosystems. Substantial research efforts are being currently devoted to predict how biodiversity will respond to global change. However, little is known on the relative importance of biodiversity against other attributes of biotic communities, such as species cover and spatial pattern, as a driver of ecosystem processes. Furthermore, the effects of global change on the relationships between these attributes and ecosystem functioning are virtually unknown. This project aims to evaluate the relationships between community attributes (species richness, composition, evenness, cover, and spatial pattern) and key processes related to ecosystem functioning under different global change scenarios. Its specific objectives are to: i) evaluate the relative importance of community attributes as drivers of ecosystem functioning, ii) assess how multiple global change drivers will affect key ecosystem processes, iii) test whether global change drivers modify observed community attributes-ecosystem functioning relationships, iv) develop models to forecast global change effects on ecosystem functioning, and v) set up protocols for the establishment of mitigation actions based on the results obtained. They will be achieved by integrating experimental and modeling approaches conducted with multiple biotic communities at different spatial scales. Such integrated framework has not been tackled before, and constitutes a ground breaking advance over current research efforts on global change. This proposal will also open the door to new research lines exploring the functional role of community attributes and their importance as modulators of ecosystem responses to global change.
Summary
Increases in nutrient availability and temperature, and changes in precipitation patterns and biodiversity are important components of global environmental change. Thus, it is imperative to understand their impacts on the functioning of natural ecosystems. Substantial research efforts are being currently devoted to predict how biodiversity will respond to global change. However, little is known on the relative importance of biodiversity against other attributes of biotic communities, such as species cover and spatial pattern, as a driver of ecosystem processes. Furthermore, the effects of global change on the relationships between these attributes and ecosystem functioning are virtually unknown. This project aims to evaluate the relationships between community attributes (species richness, composition, evenness, cover, and spatial pattern) and key processes related to ecosystem functioning under different global change scenarios. Its specific objectives are to: i) evaluate the relative importance of community attributes as drivers of ecosystem functioning, ii) assess how multiple global change drivers will affect key ecosystem processes, iii) test whether global change drivers modify observed community attributes-ecosystem functioning relationships, iv) develop models to forecast global change effects on ecosystem functioning, and v) set up protocols for the establishment of mitigation actions based on the results obtained. They will be achieved by integrating experimental and modeling approaches conducted with multiple biotic communities at different spatial scales. Such integrated framework has not been tackled before, and constitutes a ground breaking advance over current research efforts on global change. This proposal will also open the door to new research lines exploring the functional role of community attributes and their importance as modulators of ecosystem responses to global change.
Max ERC Funding
1 463 374 €
Duration
Start date: 2010-01-01, End date: 2015-09-30
Project acronym BIOCOMPLEX
Project Physical Aspects of the Evolution of Biological Complexity
Researcher (PI) Raymond Ethan Goldstein
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Call Details Advanced Grant (AdG), PE3, ERC-2009-AdG
Summary One of the most fundamental issues in evolutionary biology is the nature of transitions from single cell organisms to multicellular ones, with accompanying cellular differentiation and specialization. Not surprisingly for microscopic life in fluid environments, many of the relevant physical considerations involve diffusion, mixing, and sensing, for the efficient exchange of nutrients and metabolites with the environment is one of the most basic features of life. This proposal describes a combination of experimental and theoretical research aimed at some of the key mysteries surrounding transport and sensing by and in complex, multicellular organisms, and the implications of those findings for the explanation of driving forces behind transitions to multicellularity. There are two main components of the research. The first involves studies of single and multicellular algae which serves as model systems for allometric scaling laws in evolution. Of particular importance are the synchronization dynamics of the eukaryotic flagella that provide motility, enhance nutrient transport, and allow phototaxis in these organisms. The second thrust involves investigation of the ubiquitous phenomenon of cytoplasmic streaming in aquatic and terrestrial plants. Despite decades of research, there is no clear consensus on the metabolic role of this persistent circulation of the fluid contents of cell. Building on recent theoretical developmnts we will study its implications for internal transport and mixing, homeostasis, and development in large cells. In each case, state-of-the art experimental methods from physics, fluid dynamics, and cell biology will be used in combination with advanced theoretical methods for the study of the stochastic nonlinear PDEs that form the natural description of these systems.
Summary
One of the most fundamental issues in evolutionary biology is the nature of transitions from single cell organisms to multicellular ones, with accompanying cellular differentiation and specialization. Not surprisingly for microscopic life in fluid environments, many of the relevant physical considerations involve diffusion, mixing, and sensing, for the efficient exchange of nutrients and metabolites with the environment is one of the most basic features of life. This proposal describes a combination of experimental and theoretical research aimed at some of the key mysteries surrounding transport and sensing by and in complex, multicellular organisms, and the implications of those findings for the explanation of driving forces behind transitions to multicellularity. There are two main components of the research. The first involves studies of single and multicellular algae which serves as model systems for allometric scaling laws in evolution. Of particular importance are the synchronization dynamics of the eukaryotic flagella that provide motility, enhance nutrient transport, and allow phototaxis in these organisms. The second thrust involves investigation of the ubiquitous phenomenon of cytoplasmic streaming in aquatic and terrestrial plants. Despite decades of research, there is no clear consensus on the metabolic role of this persistent circulation of the fluid contents of cell. Building on recent theoretical developmnts we will study its implications for internal transport and mixing, homeostasis, and development in large cells. In each case, state-of-the art experimental methods from physics, fluid dynamics, and cell biology will be used in combination with advanced theoretical methods for the study of the stochastic nonlinear PDEs that form the natural description of these systems.
Max ERC Funding
2 500 000 €
Duration
Start date: 2010-01-01, End date: 2015-12-31
Project acronym BIOINCMED
Project Bioinorganic Chemistry for the Design of New Medicines
Researcher (PI) Peter John Sadler
Host Institution (HI) THE UNIVERSITY OF WARWICK
Call Details Advanced Grant (AdG), PE5, ERC-2009-AdG
Summary Bioinorganic chemistry is a rapidly expanding area of research, but the potential for the therapeutic application of metal complexes is highly underdeveloped. The basic principles required to guide the development of metal-containing therapeutic agents are lacking, despite the unique therapeutic opportunities which they offer. It is the goal of the proposed research to establish basic principles of medicinal coordination chemistry of metals that will allow the rational screening of future metallopharmaceuticals. We propose to utilize the power of inorganic chemistry to provide new knowledge of and new approaches for intervention in biological systems. This will be based on improved understanding of reactions of metal complexes under physiological conditions, on improving the specificity of their interactions, and gaining control over the potential toxicity of synthetic metal complexes. The research programme is highly interdisciplinary involving chemistry, physics, biology and pharmacology, with potential for the discovery of truly novel medicines, especially for the treatment of diseases and conditions which are currently intractable, such as cancer. The challenging and ambitious goals of the present work involve transition metal complexes with novel chemical and biochemical mechanisms of action. They will contain novel features which allow them (i) to be selectively activated by light in cells, or (ii) to be activated by a structural transition, or (ii) exhibit catalytic activity in cells. This ground-breaking research potentially has a very high impact and is based on recent discoveries in the applicant s laboratory. A feature of the programme is the use of state-of-the-art-and-beyond methodology to advance knowledge of medicinal metal coordination chemistry.
Summary
Bioinorganic chemistry is a rapidly expanding area of research, but the potential for the therapeutic application of metal complexes is highly underdeveloped. The basic principles required to guide the development of metal-containing therapeutic agents are lacking, despite the unique therapeutic opportunities which they offer. It is the goal of the proposed research to establish basic principles of medicinal coordination chemistry of metals that will allow the rational screening of future metallopharmaceuticals. We propose to utilize the power of inorganic chemistry to provide new knowledge of and new approaches for intervention in biological systems. This will be based on improved understanding of reactions of metal complexes under physiological conditions, on improving the specificity of their interactions, and gaining control over the potential toxicity of synthetic metal complexes. The research programme is highly interdisciplinary involving chemistry, physics, biology and pharmacology, with potential for the discovery of truly novel medicines, especially for the treatment of diseases and conditions which are currently intractable, such as cancer. The challenging and ambitious goals of the present work involve transition metal complexes with novel chemical and biochemical mechanisms of action. They will contain novel features which allow them (i) to be selectively activated by light in cells, or (ii) to be activated by a structural transition, or (ii) exhibit catalytic activity in cells. This ground-breaking research potentially has a very high impact and is based on recent discoveries in the applicant s laboratory. A feature of the programme is the use of state-of-the-art-and-beyond methodology to advance knowledge of medicinal metal coordination chemistry.
Max ERC Funding
1 565 397 €
Duration
Start date: 2010-07-01, End date: 2015-12-31
Project acronym BIOMEMOS
Project Higher order structure and function of biomembranes
Researcher (PI) Poul Nissen
Host Institution (HI) AARHUS UNIVERSITET
Call Details Advanced Grant (AdG), LS1, ERC-2009-AdG
Summary The biomembrane is a prerequisite of life. It enables the cell to maintain a controlled environment and to establish electrochemical gradients as rapidly accessible energy stores. Biomembranes also provide scaffold for organisation and spatial definition of signal transmission in the cell. Crystal structures of membrane proteins are determined with an increasing pace. Along with functional studies integral studies of individual membrane proteins are now widely implemented. The BIOMEMOS proposal goes a step further and approaches the function of the biomembrane at the higher level of membrane protein complexes. Through a combination of X-ray crystallography, electrophysiology, general biochemistry, biophysics and bioinformatics and including also the application of single-particle cryo-EM and small-angle X-ray scattering, the structure and function of membrane protein complexes of key importance in life will be investigated. The specific targets for investigation in this proposal include: 1) higher-order complexes of P-type ATPase pumps such as signalling complexes of Na+,K+-ATPase, and 2) development of methods for structural studies of membrane protein complexes Based on my unique track record in structural studies of large, difficult structures (ribosomes and membrane proteins) in the setting of a thriving research community in structural biology and biomembrane research in Aarhus provides a critical momentum for a long-term activity. The activity will take advantage of the new possibilities offered by synchrotron sources in Europe. Furthermore, a single-particle cryo-EM research group formed on my initiative in Aarhus, and a well-established small-angle X-ray scattering community provides for an optimal setting through multiple cues in structural biology and functional studies
Summary
The biomembrane is a prerequisite of life. It enables the cell to maintain a controlled environment and to establish electrochemical gradients as rapidly accessible energy stores. Biomembranes also provide scaffold for organisation and spatial definition of signal transmission in the cell. Crystal structures of membrane proteins are determined with an increasing pace. Along with functional studies integral studies of individual membrane proteins are now widely implemented. The BIOMEMOS proposal goes a step further and approaches the function of the biomembrane at the higher level of membrane protein complexes. Through a combination of X-ray crystallography, electrophysiology, general biochemistry, biophysics and bioinformatics and including also the application of single-particle cryo-EM and small-angle X-ray scattering, the structure and function of membrane protein complexes of key importance in life will be investigated. The specific targets for investigation in this proposal include: 1) higher-order complexes of P-type ATPase pumps such as signalling complexes of Na+,K+-ATPase, and 2) development of methods for structural studies of membrane protein complexes Based on my unique track record in structural studies of large, difficult structures (ribosomes and membrane proteins) in the setting of a thriving research community in structural biology and biomembrane research in Aarhus provides a critical momentum for a long-term activity. The activity will take advantage of the new possibilities offered by synchrotron sources in Europe. Furthermore, a single-particle cryo-EM research group formed on my initiative in Aarhus, and a well-established small-angle X-ray scattering community provides for an optimal setting through multiple cues in structural biology and functional studies
Max ERC Funding
2 444 180 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
Project acronym BIOSENSORIMAGING
Project Hyperpolarized Biosensors in Molecular Imaging
Researcher (PI) Leif Schröder
Host Institution (HI) FORSCHUNGSVERBUND BERLIN EV
Call Details Starting Grant (StG), LS7, ERC-2009-StG
Summary Xenon biosensors have an outstanding potential to increase the significance of magnetic resonance imaging (MRI) in molecular imaging and to combine the advantages of MRI with the high sensitivity of hyperpolarized Xe-129 and the specificity of a functionalized contrast agent. Based on new detection schemes (Hyper-CEST method) in Xe MRI, this novel concept in molecular diagnostics will be made available for biomedical applications. The advancement focuses on high-sensitivity in vitro diagnostics for localization of tumour cells in cell cultures and first demonstrations on animal models based on a transferrin-functionalized biosensor. Such a sensor will enable detection of subcutaneous tumours at high sensitivity without any background signal. More detailed work on the different available Hyper-CEST contrast parameters focuses on an absolute quantification of new molecular markers that will improve non-invasive tumour diagnostics significantly. NMR detection of functionalized Xe biosensors have the potential to close the sensitivity gap between modalities of nuclear medicine like PET/SPECT and MRI without using ionizing radiation or making compromises in penetration depth like in optical methods.
Summary
Xenon biosensors have an outstanding potential to increase the significance of magnetic resonance imaging (MRI) in molecular imaging and to combine the advantages of MRI with the high sensitivity of hyperpolarized Xe-129 and the specificity of a functionalized contrast agent. Based on new detection schemes (Hyper-CEST method) in Xe MRI, this novel concept in molecular diagnostics will be made available for biomedical applications. The advancement focuses on high-sensitivity in vitro diagnostics for localization of tumour cells in cell cultures and first demonstrations on animal models based on a transferrin-functionalized biosensor. Such a sensor will enable detection of subcutaneous tumours at high sensitivity without any background signal. More detailed work on the different available Hyper-CEST contrast parameters focuses on an absolute quantification of new molecular markers that will improve non-invasive tumour diagnostics significantly. NMR detection of functionalized Xe biosensors have the potential to close the sensitivity gap between modalities of nuclear medicine like PET/SPECT and MRI without using ionizing radiation or making compromises in penetration depth like in optical methods.
Max ERC Funding
1 848 600 €
Duration
Start date: 2009-12-01, End date: 2014-11-30
Project acronym BIOTIME
Project Biological diversity in an inconstant world: temporal turnover in modified ecosystems
Researcher (PI) Anne Elizabeth Magurran
Host Institution (HI) THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS
Call Details Advanced Grant (AdG), LS8, ERC-2009-AdG
Summary This project addresses a key issue in fundamental research - one that has challenged ecologists ever since Darwin s time that is why some species are common, and others rare, and why, despite marked turnover at the level of individual species abundances, the structure of a community is generally conserved through time. Its aim is to examine the temporal dynamics of species abundance distributions (SADs), and to assess the capacity of these distributions to withstand change (resistance) and to recover from change (resilience). These are topical and important questions given the increasing impact that humans are having on the natural world. There are three components to the research. First, we will model SADs and predict responses to a range of events including climate change and the arrival of invasive species. A range of modeling approaches (including neutral, niche and statistical) will be adopted; by incorporating temporal turnover in hitherto static models we will advance the field. Second, we will test predictions concerning the resistance and resilience of SADs by a comparative analysis of existing data sets (that encompass communities in terrestrial, freshwater and marine environments for ecosystems extending from the poles to the tropics) and through a new field experiment that quantifies temporal turnover across a community (unicellular organisms to vertebrates) in relation to factors both natural (dispersal limitation) and anthropogenic (human disturbance) thought to shape SADs. In the final part of the project we will apply these new insights into the temporal dynamics of SADs to two important conservation challenges. These are 1) the conservation of biodiversity in a heavily utilized European landscape (Fife, Scotland) and 2) the conservation of biodiversity in Mamirauá and Amaña reserves in Amazonian flooded forest. Taken together this research will not only shed new light on the structure of ecological communities but will also aid conservation.
Summary
This project addresses a key issue in fundamental research - one that has challenged ecologists ever since Darwin s time that is why some species are common, and others rare, and why, despite marked turnover at the level of individual species abundances, the structure of a community is generally conserved through time. Its aim is to examine the temporal dynamics of species abundance distributions (SADs), and to assess the capacity of these distributions to withstand change (resistance) and to recover from change (resilience). These are topical and important questions given the increasing impact that humans are having on the natural world. There are three components to the research. First, we will model SADs and predict responses to a range of events including climate change and the arrival of invasive species. A range of modeling approaches (including neutral, niche and statistical) will be adopted; by incorporating temporal turnover in hitherto static models we will advance the field. Second, we will test predictions concerning the resistance and resilience of SADs by a comparative analysis of existing data sets (that encompass communities in terrestrial, freshwater and marine environments for ecosystems extending from the poles to the tropics) and through a new field experiment that quantifies temporal turnover across a community (unicellular organisms to vertebrates) in relation to factors both natural (dispersal limitation) and anthropogenic (human disturbance) thought to shape SADs. In the final part of the project we will apply these new insights into the temporal dynamics of SADs to two important conservation challenges. These are 1) the conservation of biodiversity in a heavily utilized European landscape (Fife, Scotland) and 2) the conservation of biodiversity in Mamirauá and Amaña reserves in Amazonian flooded forest. Taken together this research will not only shed new light on the structure of ecological communities but will also aid conservation.
Max ERC Funding
1 812 782 €
Duration
Start date: 2010-08-01, End date: 2016-01-31
Project acronym BODYBUILT
Project Building The Vertebrate Body
Researcher (PI) Olivier Pourquie
Host Institution (HI) CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE
Call Details Advanced Grant (AdG), LS3, ERC-2009-AdG
Summary My lab is interested in the development of the tissue that gives rise to vertebrae and skeletal muscles called the paraxial mesoderm. A striking feature of this tissue is its segmental organization and we have made major contributions to the understanding of the molecular control of the segmentation process. We identified a molecular oscillator associated to the rhythmic production of somites and proposed a model for vertebrate segmentation based on the integration of a rhythmic signaling pulse gated spatially by a system of traveling FGF and Wnt signaling gradients. We are also studying the differentiation of paraxial mesoderm precursors into the muscle, cartilage and dermis lineages. Our work identified the Wnt, FGF and Notch pathways as playing a prominent role in the patterning and differentiation of paraxial mesoderm. In this application, we largely focus on the molecular control of paraxial mesoderm development. Using microarray and high throughput sequencing-based approaches and bioinformatics, we will characterize the transcriptional network acting downstream of Wnt, FGF and Notch in the presomitic mesoderm (PSM). We will also use genetic and pharmacological approaches utilizing real-time imaging reporters to characterize the pacemaker of the segmentation clock in vivo, and also in vitro using differentiated embryonic stem cells. We further propose to characterize in detail a novel RA-dependent pathway that we identified and which controls the somite left-right symmetry. Our work is expected to have a strong impact in the field of congenital spine anomalies, currently an understudied biomedical problem, and will be of utility in elucidating the etiology and eventual prevention of these disorders. This work is also expected to further our understanding of the Notch, Wnt, FGF and RA signalling pathways which are involved in segmentation and in the establishment of the vertebrate body plan, and which play important roles in a wide array of human diseases.
Summary
My lab is interested in the development of the tissue that gives rise to vertebrae and skeletal muscles called the paraxial mesoderm. A striking feature of this tissue is its segmental organization and we have made major contributions to the understanding of the molecular control of the segmentation process. We identified a molecular oscillator associated to the rhythmic production of somites and proposed a model for vertebrate segmentation based on the integration of a rhythmic signaling pulse gated spatially by a system of traveling FGF and Wnt signaling gradients. We are also studying the differentiation of paraxial mesoderm precursors into the muscle, cartilage and dermis lineages. Our work identified the Wnt, FGF and Notch pathways as playing a prominent role in the patterning and differentiation of paraxial mesoderm. In this application, we largely focus on the molecular control of paraxial mesoderm development. Using microarray and high throughput sequencing-based approaches and bioinformatics, we will characterize the transcriptional network acting downstream of Wnt, FGF and Notch in the presomitic mesoderm (PSM). We will also use genetic and pharmacological approaches utilizing real-time imaging reporters to characterize the pacemaker of the segmentation clock in vivo, and also in vitro using differentiated embryonic stem cells. We further propose to characterize in detail a novel RA-dependent pathway that we identified and which controls the somite left-right symmetry. Our work is expected to have a strong impact in the field of congenital spine anomalies, currently an understudied biomedical problem, and will be of utility in elucidating the etiology and eventual prevention of these disorders. This work is also expected to further our understanding of the Notch, Wnt, FGF and RA signalling pathways which are involved in segmentation and in the establishment of the vertebrate body plan, and which play important roles in a wide array of human diseases.
Max ERC Funding
2 500 000 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
